Relationship between brain-derived neurotrophic factor and mild to moderate cognitive impairment in the older Mexican population

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The brain-derived neurotrophic factor is a regulator of synaptic plasticity, neuronal survival, and differentiation, including a critical molecular target for drug development in neurological disorders. There are no studies on BDNF and mild to moderate cognitive impairment in the Mexican population. Therefore, it is essential to explore early expression biomarkers that contribute to early detection and benefit the prognostic outlook of these patients.IntroductionAccording to World Population Prospects 2019 (United Nations, 2019), by 2050, 1 in 6 people in the world will be over the age of 65, up from 1 in 11 in 2019<a class="elsevierStyleCrossRef" href="#bb0005">1</a>. This rapid demographic aging will increase the prevalence of disease and disabilities, with an expected particular emphasis on the impairment of cognitive functions<a class="elsevierStyleCrossRef" href="#bb0010">2</a>.Cognitive deficit is a syndrome characterized by a decline in cognitive functions more significant than expected for age and individual educational level, which does not significantly interfere with activities of daily living<a class="elsevierStyleCrossRef" href="#bb0015">3</a>.The term cognitive impairment was introduced in the late 1980s by Reisberg et al. (1988) to characterize people in this intermediate stage<a class="elsevierStyleCrossRef" href="#bb0020">4</a>. Petersen et al. (1999) further developed the concept by proposing criteria based on an observational study of aging<a class="elsevierStyleCrossRef" href="#bb0025">5</a>. In 2003, derived from the symposium, the international standards for moderate cognitive impairment were published<a class="elsevierStyleCrossRef" href="#bb0030">6</a>.Cognitive impairment and dementia represent conditions that affect the quality of life of the elderly population and determine a greater use of health services. Cognitive impairment constitutes a high-risk condition for the appearance of dementia, with a probability of developing it of 10–15% per year, compared to healthy controls, where it is 1–2%<a class="elsevierStyleCrossRef" href="#bb0035">7</a>.Dementia is one of the determinants for the development of dependency and functional deterioration in adults over 75 years of age, with the consequent burden for the primary caregiver, in addition to being a strong predictor of mortality, with a risk of 2–3 times greater when compared to other chronic diseases that reduce life expectancy<a class="elsevierStyleCrossRef" href="#bb0040">8</a>.Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors involved in the differentiation<a class="elsevierStyleCrossRef" href="#bb0045">9</a>, maturation<a class="elsevierStyleCrossRef" href="#bb0050">10</a>, and survival of neurons in the nervous system<a class="elsevierStyleCrossRef" href="#bb0055">11</a>. It shows a neuroprotective effect under adverse conditions, such as glutamatergic stimulation, cerebral ischemia, hypoglycemia, and neurotoxicity<a class="elsevierStyleCrossRef" href="#bb0060">12</a>. BDNF stimulates and controls neurogenesis<a class="elsevierStyleCrossRef" href="#bb0065">13</a>,<a class="elsevierStyleCrossRef" href="#bb0070">14</a>.BDNF contains 11 exons. It encompasses approximately 70 kB and is located on chromosome 11p<a class="elsevierStyleCrossRef" href="#bb0075">15</a>, which consists of a mature isoform of 118 amino acids that specifically binds to the tropomyosin kinase B receptor, increasing the excitatory synapse and inhibiting GABAergic neuronal synapse<a class="elsevierStyleCrossRef" href="#bb0080">16</a>. BDNF protein and mRNA have been identified in most brain areas, including the olfactory bulb, cortex, hippocampus, basal forebrain, midbrain, hypothalamus, brainstem, and spinal cord. A critical role in regulating plastic changes in the adult brain, including regulation of NMDAR transport, phosphorylation, and expression levels. BDNF has been postulated to be an essential part of the cellular mechanism for memory formation and maintenance by promoting synaptic consolidation<a class="elsevierStyleCrossRef" href="#bb0085">17</a>.BDNF plays a vital role in cognitive alterations related to hippocampal atrophy and structures involved in memory. Low serum levels have been associated with reduced Folstein Mini-Mental State Examination (MMSE) scores in patients with dementia. Komulainen et al. (2008) found that BDNF levels were associated with cognitive function in older women, suggesting that plasma BDNF may be a clinically relevant biomarker<a class="elsevierStyleCrossRef" href="#bb0090">18</a>. Shimada et al. (2014) reported lower levels of BDNF associated with lower scores and moderate cognitive impairment<a class="elsevierStyleCrossRef" href="#bb0095">19</a>.This study aims to compare BNDF serum levels in a Mexican adult population with mild to moderate cognitive impairment and controls.MethodsCase–control study in patients diagnosed with mild to moderate cognitive impairment and patients without cognitive impairment as a control group in a highly specialized hospital in northwestern Mexico.Study populationOur study evaluated 191 people who were users of the Instituto Mexicano del Seguro Social (IMSS) in the period from February 2020 to February 2021. To be included, each participant was 55 years old or older at the time of the study and did not have participated in other studies. Patients with current severe medical conditions (e.g., recent myocardial infarction, decompensated heart failure, metabolic imbalance, hydroelectrolytic disturbances), neurological or psychiatric history (e.g., cerebrovascular accident, Alzheimer's disease, schizophrenia, mental disorder, bipolar, depression) were excluded. Patients who do not sign an informed consent letter or with missing data were excluded.Cognitive impairment criteria and cognitive function testsWe defined cognitive impairment based on previous studies (Petersen et al., 2014), using the following criteria: (1) self-reported or family-reported memory complaint; (2) objective memory impairment (indicated by an age-adjusted score of at least 1.5 SD below the lower reference limit of tests used for neuropsychological assessments); (3) no evidence of functional dependency; (4) exclusion of people with criteria for dementia.<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="li0005">1.Screening for cognitive impairment includes a standardized face-to-face interview to collect sociodemographic, anthropometric, medical history, and functional status data, along with tests of cognitive function using the Mini-Mental State Examination (MMSE®) and Montreal Cognitive Assessment (MoCA®), scales are validated in the Mexican population;<a class="elsevierStyleCrossRef" href="#bb0100">20</a>,<a class="elsevierStyleCrossRef" href="#bb0105">21</a> both scales simultaneously, considering the patient's comfort and compliance to continue with the evaluations.</li></ul>The study complied with the principles of the Declaration of Helsinki. All participants gave their informed consent to participate in this study; the study protocol was authorized with the registration number (R-2020-1002-010) by the ethics committee in health research of the High Specialty Medical Unit (IMSS- UMAE No. 71), Torreon, Coahuila, Mexico.Assessment of cognitive impairmentThe Folstein Mini-Mental State (MMSE®) and Montreal Cognitive Assessment (MoCA®) scales were applied to determine the cognitive function and screening for cognitive impairment. Standard cut-off points for MMSE® normal (MMSE 24–30), mild (20–23), moderate (MMSE 10–19), and severe (MMSE <9) were used based on previous studies (Benoit et al., 2020). For MoCA®, the following cut-off points were used for normal (MoCA >26), mild (MoCA 18–25), moderate (MoCA 10–17), and severe (MoCA <10) classification according to provider recommendations.Based on the scores obtained, the participants were classified into 2 large groups: those with cognitive impairment (cases) and participants without cognitive impairment (controls). The flow of participants can be seen in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>.<elsevierMultimedia ident="t0005"></elsevierMultimedia>Sample collectionParticipants were instructed to attend the sample collection after fasting for 8 h. The blood sample was obtained by venipuncture, with a pool in a BD Vacutainer® SST™ tube of 6 mL whole blood. The model coagulation was at room temperature for 30 min and subsequent centrifugation at 2500 rpm/min for 20 min; the serum was stored at a temperature of −80 °C for further analysis.Quantitative determination of serum levels of BDNFQuantitative determination of BDNF levels in serum was analyzed using a commercial kit (BDNF Human ELISA kit, Aviscera Biosciences, Santa Clara, CA, USA) following the manufacturer's instructions. Serum samples were diluted in polypropylene test tubes 40 times (10 μL sample+390 μL dilution buffer). Samples were added to the 96-well flat bottom plate and then shaken for 2 h at room temperature. Subsequently, after washing 4 times, a detection antibody was added to each well, and the plates were incubated for 2 h under constant agitation at room temperature. After another washing step, horseradish peroxidase-conjugated streptavidin was added, and the plates were incubated for 60 min at room temperature, protected from light. Unbound streptavidin was discarded, and TMB substrate solution was added. The reaction was stopped 15 min later. Optical density was measured in a microplate reader (Stat Fax® 4700 Awareness Technology, USA) at a 450±3 nm wavelength proportional to the BDNF concentration. The intra- and inter-assay variations of BDNF were less than 9%. BDNF concentrations were determined according to the BDNF standard curve. All assays were duplicated, and results were expressed in pg/ml.Statistical analysisThe Chi-square homogeneity test was used to compare cognitive impairment with the categorical variables of the control group and cases. Student's t-test was applied to compare cognitive impairment with BDNF levels with normal distribution or Mann–Whitney's U test for non-normal distribution. Differences in serum BDNF concentrations were performed by one-way analysis of variance (ANOVA) in both sexes. All statistical comparisons were performed at a significance level of p<.05, and all statistical and data management calculations were performed using the scikitlearn®, scipy®, and pandas® Library Software Package in the scikitlearn®, scipy®, and pandas® programming language Python®.ResultsOne hundred ninety-one patients were included in the study; the main characteristics of the participants are in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>. The mean age of the participants was 65.77±8.15. The average schooling was 10.92±4.55 years. Eighty-one women (42%) and 110 men (58%) were included in the study. The average score of the participants in general in the MMSE® instrument was 25.67±3.63, and using the MoCA® tool, 24.34±3.51.The mean age for the case group was 67.5±8.43, and for the control group, it was 63.7±7.38. Regarding gender, in the case group, there are 53 men (52%) and 49 women (48%); in the control group, there are 57 men (64%) and 32 women (36%). The number of years of study in the case group was 8.98+3.96; for the control group, it was 13.15+4.17.Regarding the score obtained by the MoCA® instrument in the group of cases, 94 patients were classified as having a mild cognitive impairment (92.1%); 8 patients were classified as having a moderate cognitive impairment (7.8%), and no patients were classified as having severe cognitive impairment. Using the MMSE® instrument, 94 patients with mild cognitive impairment (92.1%), 6 with moderate cognitive impairment (5.8%), and 2 patients with severe cognitive impairment (1.9%) were classified from the case group. The mean serum concentration of BDNF in the case group was 277.68±75.09 vs. the control group, where the concentration was 354.97±66.06 pg/ml (p=.001).As shown in <a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>, mean BDNF levels were higher in females. Likewise, we can observe in <a class="elsevierStyleCrossRef" href="#f0010">Fig. 2</a> that according to the level of schooling, the level of BDNF increases.<elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia>BDNF concentrations varied according to the classification of cognitive impairment based on the MMSE® and MoCA® tests (<a class="elsevierStyleCrossRefs" href="#f0015">Figs. 3 and 4</a>).<elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="f0020"></elsevierMultimedia>The correlation was made between the variables with the serum level of BDNF, shown in <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>. where it was found that there is a correlation between BDNF and cardiovascular diseases, years of schooling, MMSE score, and MOCA score. Moreover, the general distribution of the BDNF marker shows a normal distribution curve (<a class="elsevierStyleCrossRef" href="#f0025">Fig. 5</a>), which is why the ANOVA F value analysis is performed (<a class="elsevierStyleCrossRef" href="#f0030">Fig. 6</a>).<elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia><elsevierMultimedia ident="f0030"></elsevierMultimedia>The statistical analysis presented in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a> and the accompanying ANOVA F value in <a class="elsevierStyleCrossRef" href="#f0030">Fig. 6</a> is a comprehensive view of the significance of the variables present in our study. The p-values in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a> reveal that ‘Education’, ‘MOCA score’, ‘MMSE score’, and ‘BDNF pg/ml’ with values below 0.05, indicating significant statistical relevance. This is supported by the ANOVA F-value analysis in <a class="elsevierStyleCrossRef" href="#f0030">Fig. 6</a>, where the corresponding F-values for these variables are markedly high, with the ‘MOCA score’ peaking at 41.62, highlighting its substantial influence. Conversely, ‘BMI’ demonstrates a p-value of 0.492, paired with a relatively low F-value, indicating that it does not have a significant association. The alignment of low p-values with high F-values confirms the robustness of the variables' impact, underscoring their importance in the research findings. These statistical measures collectively highlight the variables most critical to the study's conclusions and those that may be considered less influential.<elsevierMultimedia ident="t0015"></elsevierMultimedia>DiscussionOur study aimed to compare serum BDNF levels in Mexican patients with mild–moderate cognitive impairment and a control group from a high-specialty hospital.The number of people worldwide with cognitive impairment in 2000 was approximately 20 million; this figure will reach 81.1 million in 2040. Several studies have shown that neurotrophic factors such as BDNF are involved in the pathophysiology of neurodegenerative diseases. Higher serum BDNF levels are associated with better MoCA® / MMSE® test performance.In the present study, we found that patients with moderate, mild cognitive impairment determined by the MoCA® / MMSE® score have a lower serum level of BDNF than subjects with normal scores in these instruments. The mean serum concentration of BDNF in the case group was 277.68±75.09 vs. the control group with 354.97±66.06 pg/ml (p=.001).Laske et al. (2006) found that early-stage patients with MMSE scores ≥21 (mean 25.5) had significantly higher serum BDNF levels compared with late-stage patients with MMSE scores <21 (mean 25.5). and age-matched healthy controls. The mean age of their case group was 71.7±7.0, and the control group was 70.3±5.4. The mean MMSE® score for the case group was 19.2±7.0, and the control group was 29.5±0.2. It was found that in the control group, the mean concentration of BDNF was 20.7±5.2 ng/ml; in the initial stages of the disease, it was 25.1±4.1 ng/ml vs. the group in the final stages, where the mean concentration was 17.3±4.4 ng/ml (p<.0001). There was a correlation between the serum level of BDNF and the score obtained in the MMSE® instrument (r=0.486; p<.0001).Yu et al. (2008) looked for an association between serum BDNF levels and patients with mild cognitive impairment. They recruited 99 patients with a previous diagnosis of mild cognitive impairment and 99 healthy patients. Serum levels of BDNF were determined. They reported in their study that serum BDNF concentrations in patients with mild cognitive impairment ([interquartile range]=4.37 [2.35–6.40] ng/ml) were significantly lower than in healthy controls (4.98 [3.50–7.33] ng/ml) (z=−2.449, p=.014). with a positive correlation between BDNF and delayed memory scores on the auditory verbal learning test, reflecting episodic memory (r=0.264, p=.008). This study suggests that reduced levels of BDNF may play a role in the pathophysiology of mild cognitive impairment.Murillo-Ortiz et al. (2016) in their study included 40 patients with type 2 diabetes mellitus (mean age 51.88±12.81) and 40 healthy patients (mean age 42.30±12.87). MMSE® was performed to classify them into 2 groups: with or without cognitive impairment. The mean score using the MMSE® instrument was 20.26±2.15 for the case group and 25.44±1.50 for the control group (p=.0001). BDNF determination was performed in both groups, finding a statistically significant difference (31.55±10.24 vs. 43.78±9.05, p=.005).The mentioned authors' results support our research findings, showing that lower scores in instruments such as MMSE® and MoCA® were associated with lower serum concentrations of BDNF. These studies use MMSE® to measure cognitive status and classify patients with or without cognitive impairment, which is consistent with our research methodology. They report meaning MMSE® scores of 20.26±2.15 for the case group and 25.44±1.50 for the control group. In our study, the mean score for the case group was 21.92±3.06; for the control group, it was 28.2±1.45. The serum concentrations of BDNF were lower in the case group vs. the control group, showing a difference with statistical significance. These results agree with what was previously reported. There is a certain degree of variability between their groups' scores and serum BDNF concentrations concerning ours, but they generally present the same trend.As secondary results, it can be observed that there is a correlation between BDNF and cardiovascular diseases, schooling in years, MMSE® score, and MOCA® score. Moreover, the p-value and ANOVA F value analysis confirm these variables' importance and impact on the BDNF levels.There is disagreement between the different publications on BDNF levels concerning gender. Some publications suggest that estrogens have a positive regulatory effect on BDNF expression and signaling. However, these observations were generated from fragmented studies, which were not primarily designed to examine the tissue distribution of BDNF in different sexes<a class="elsevierStyleCrossRef" href="#bb0110">22</a>. In our study, estrogen levels were not quantified, so we cannot infer this relationship.Hashimoto (2016) conducted a study to determine if there is a difference between serum levels of BDNF based on ethnic origin; according to the study by Yoshida (2012), the Japanese population shows a mean level of BDNF of 23.11±5.90 ng/ml; Sodersten (2014) reported 30.3±7.2 ng/ml for the Swedish people and Levin (2015) for the Jewish population 14.0±8.9 ng/ml. Therefore, there is evidence that the concentration varies according to ethnic origin.Shimada et al. (2014) reported that serum BDNF levels are lower in patients with mild cognitive impairment (OR, 95%, CI 1.41, 1.00–1.99). Patients older than 65 years were included in this study, and those with established neurological diseases were excluded. They found that BDNF levels varied by gender for men (20.8±5.6 ng/ml) and women (21.2±5.2 ng/ml; t=2.162, df=4394, p=.031). In both groups, serum BDNF levels were associated with age (β=0.123, t=5.750, p<.001). Serum levels of BDNF were associated with a decrease in memory and calculation tests (β=0.027, t=1.958, p<.05). Finding that age presented an OR for mild cognitive impairment of 1.00 (95% CI 0.99–1.02; p=.977), gender of 0.85 (95% CI 0.71–1.00; p=.051), education 0.82 (95% CI 0.79–0.85; p=<.001) and type 2 diabetes mellitus of 1.04 (95% CI 0.82–1.31; p=.23).Villela-Nunes et al. (2018) included 80 deceased participants with a diagnosis of dementia and depression in their study, compared with a control group of 80 deceased patients without these diagnoses. Patients with traumatic death, neoplasms, severe systemic diseases, and unknown causes of death were excluded. The mean age for the case group was 73.9±11.3, for the control group 74.9±11.1 (p=.58), in the case group, there were 15 patients with cardiovascular disease (18.75%), and in the case group 14 patients with this condition (17.5%) (p=.84). BDNF determination was performed in the prefrontal cortex, reporting lower levels in the case group vs. the control group (ß=-0.106, 95%CI=−0.204; −0.009, p=.034). They did not note differences in other variables, such as diabetes mellitus, cardiovascular diseases, and depression.Concordance is found between the characteristics of our population and the previously reported studies, except for cardiovascular disease, since 56% of our participants declared themselves with this diagnosis. According to national statistics in Mexico, it is estimated that 70.3% of the adult population has at least one cardiovascular disease. The prevalence of obesity in the country in the adult population is 33.6%, according to ENSANUT data; in our study, a majority of 26% was reported.A difference can be observed between the mean concentration of BDNF in our population and that of other studies. The enormous heterogeneity of published serum BDNF levels is mainly due to methodological issues, which need to be more noticed in quite a few publications (e.g., sample storage conditions, effects of repeated freeze–thaw cycles, and the different ELISA kits used).The strengths of the present study include the large sample size, as we matched the size of previous studies—comprehensive measurement of cognitive function by implementing both widely validated tests in the Mexican population. The analysis of other variables that could affect the result, such as diabetes mellitus and cardiovascular diseases, is closely correlated with mild cognitive impairment—having rigorous exclusion criteria that could influence the outcome. Blood samples were taken at times reported in other studies to avoid the influence of circadian cycles on the result.The limitations of the present study include that it is a cross-sectional study, which did not have a database, and limited blinding since the same person who applied the tests to measure cognitive abilities was involved in processing samples and results. The heterogeneity of our population with a medical affiliation is evident, which limited the power to match the groups, showing in the clinical characteristics a tendency of the group of cases to suffer more cardiovascular diseases.Although our study was population-based, further prospective research is needed to validate the use of serum BDNF levels to discriminate the risk of cognitive decline.ConclusionIn patients from the study population of cases and controls, utilizing the MoCA® and MMSE® screening test and serum marker analysis BDNF, there is a significant difference between control groups and patients with cognitive impairment in any of its clinical stages.The mean serum concentration of BDNF in the case group was 277.68±75.09 vs. the control group of 354.97±66.06 pg/ml (p=.001).The level of BDNF was found in both groups, with a lower concentration in the male gender compared to the female gender, as well as a higher level of biomarker related to schooling (Master's degree) in both groups.The following are the supplementary data related to this article.<elsevierMultimedia ident="f0035"></elsevierMultimedia><elsevierMultimedia ident="f0040"></elsevierMultimedia>Supplementary data to this article can be found online at <a href="https://doi.org/10.1016/j.neurop.2024.100158">https://doi.org/10.1016/j.neurop.2024.100158</a>.Financial SupportThe researchers have yet to receive financial support for this article's research, authorship, and publication.Approval by the Ethics CommitteeRegistration number R-2020-1002-010.Author contributionsStudy design and conception by ER, CA, HA, FJ, and MP; Experiments were performed by ER, CA, HA, FJ, and MP; and Data analysis by MP, ER, and CA. All authors contributed to the writing and review." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2237595" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "as0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1872740" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2237596" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "as0030" "titulo" => "Fundamento" ] 1 => array:2 [ "identificador" => "as0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "as0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "as0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "as0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1872741" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Justification" ] 5 => array:2 [ "identificador" => "s0010" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "s0015" "titulo" => "Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "s0020" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "s0025" "titulo" => "Cognitive impairment criteria and cognitive function tests" ] 2 => array:2 [ "identificador" => "s0030" "titulo" => "Assessment of cognitive impairment" ] 3 => array:2 [ "identificador" => "s0035" "titulo" => "Sample collection" ] 4 => array:2 [ "identificador" => "s0040" "titulo" => "Quantitative determination of serum levels of BDNF" ] 5 => array:2 [ "identificador" => "s0045" "titulo" => "Statistical analysis" ] ] ] 7 => array:2 [ "identificador" => "s0050" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "s0055" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "s0060" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "s0065" "titulo" => "Financial Support" ] 11 => array:2 [ "identificador" => "s0070" "titulo" => "Approval by the Ethics Committee" ] 12 => array:2 [ "identificador" => "s0075" "titulo" => "Author contributions" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-05-25" "fechaAceptado" => "2024-01-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1872740" "palabras" => array:2 [ 0 => "Cognitive impairment" 1 => "Brain-derived neurotrophic factor BDNF" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1872741" "palabras" => array:2 [ 0 => "Deterioro cognitivo" 1 => "Factor neurotrófico derivado del cerebro BDNF" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundMild–moderate cognitive impairment is a frequent pathology in the adult population. It is important to explore early expression biomarkers that contribute to early detection and benefit the prognostic outlook. Brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, neuronal survival, and differentiation, and even a critical molecular target for drug development in neurological disorders. It is crucial to carry out studies in the early stages that better clarify the landscape of BDNF. ObjectiveTo compare the serum levels of BDNF in healthy adult patients and those with mild to moderate cognitive impairment. Materials and methodsA casecontrol study in patients over 55- years with cognitive impairment, obtained by the MMSE® and MoCA® screening scales. A total of 191 patients, 102 patients with cognitive impairment (cases) and 89 healthy ones (controls) participated in the study. Blood samples were collected to obtain serum, with the determination of BDNF concentrations. For differences in BDNF concentrations, a one-way analysis of variance was used. The significance level of p<.05. ResultsThe mean serum concentration of BDNF in the case group was 277.68±75.09 vs. the control group, where the concentration was 354.97±66.06 pg/ml (p=.001). ConclusionsThere is an association between decreased BDNF levels and mild and moderate cognitive impairment in our study population." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "as0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "FundamentoEl deterioro cognitivo leve-moderado es una patología frecuente en la población adulta mayor. Es importante explorar biomarcadores de expresión temprana que contribuyan a la detección temprana y beneficien el pronóstico. El factor neurotrófico derivado del cerebro (BDNF) es un regulador esencial de la plasticidad sináptica, la supervivencia y la diferenciación neuronal e incluso un objetivo molecular crítico para el desarrollo de fármacos en trastornos neurológicos. Es fundamental realizar estudios en las primeras etapas que aclaren mejor el panorama del BDNF. ObjetivoComparar los niveles séricos de BDNF en pacientes adultos sanos y aquellos con deterioro cognitivo leve a moderado. Materiales y métodosEstudio de casos y controles en pacientes mayores de 55 años con deterioro cognitivo, obtenidos mediante las escalas de MMSE® y MoCA®. Participaron en el estudio un total de 191 pacientes, 102 pacientes con deterioro cognitivo (casos) y 89 sanos (controles). Se recogieron muestras de sangre para obtener suero, con determinación de concentraciones de BDNF. Para las diferencias en las concentraciones de BDNF, se utilizó un análisis de varianza unidireccional ANOVA. El nivel de significancia de p < 0,05. ResultadosLa concentración sérica media de BDNF en el grupo de casos fue de 277,68 ± 75,09 vs. el grupo control, donde la concentración fue de 354,97 ± 66,06 pg. /mL (P = 0,001). Conclusionesexiste asociación entre niveles disminuidos de BDNF y deterioro cognitivo leve y moderado en nuestra población de estudio." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "as0030" "titulo" => "Fundamento" ] 1 => array:2 [ "identificador" => "as0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "as0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "as0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "as0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:5 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "https://orcid.org/0000-0001-7677-5361." "identificador" => "fn0005" ] 1 => array:3 [ "etiqueta" => "2" "nota" => "https://orcid.org/0000-0001-7153-215X." "identificador" => "fn0010" ] 2 => array:3 [ "etiqueta" => "3" "nota" => "https://orcid.org/0000-0003-3537-6422." "identificador" => "fn0015" ] 3 => array:3 [ "etiqueta" => "4" "nota" => "https://orcid.org/0000-0002-3760-1876." "identificador" => "fn0020" ] 4 => array:3 [ "etiqueta" => "5" "nota" => "https://orcid.org/0000-0001-5448-7975." "identificador" => "fn0025" ] ] "multimedia" => array:11 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1226 "Ancho" => 1637 "Tamanyo" => 81865 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mean BDNF pg/ml values by gender in cases group." ] ] 1 => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1315 "Ancho" => 1637 "Tamanyo" => 117224 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mean BDNF pg/ml values by education category in cases." ] ] 2 => array:8 [ "identificador" => "f0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1238 "Ancho" => 1635 "Tamanyo" => 98782 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "BDNF behavior according to classification by MMSE (Mini-Mental State Examination)." ] ] 3 => array:8 [ "identificador" => "f0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1238 "Ancho" => 1635 "Tamanyo" => 95244 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "BDNF behavior according to classification by MoCA." ] ] 4 => array:8 [ "identificador" => "f0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1195 "Ancho" => 2244 "Tamanyo" => 191039 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Distribution of BDNF (pg/ml) in the general study population." ] ] 5 => array:8 [ "identificador" => "f0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1531 "Ancho" => 1637 "Tamanyo" => 130960 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0030" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Feature importances in the BDNF and cognitive impairment study, ANOVA F-value analysis." ] ] 6 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Measure</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=102 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=89 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, years, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.50 (8.43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.79 (7.38) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Education, years, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.98 (3.96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.15 (4.17) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male sex, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MMSE® score (0–30) mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.46 (3.53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.20 (1.45) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MoCA® score (0–30) mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.92 (3.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.10 (1.20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertension, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Heart disease, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.88 (3.56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.26 (3.56) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal weight (BMI <25) % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Overweight (BMI 25–30) % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Obesity (BMI >30) % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BDNF expression, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">277.68 (75.09) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">354.97 (66.06) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3647222.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic characteristics between study groups." ] ] 7 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Correlation of numerical variables concerning BDNF (pg/ml)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medical and demographic variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BDNF (pg/ml) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.275441 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.116012 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Arterial hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.072353 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type II diabetes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.029303 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005882 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.049353 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Schooling (Years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.21489 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MMSE® score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.342508 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MoCA® score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.426976 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BDNF (pg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3647221.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Correlation of numerical variables concerning BDNF pg/ml." ] ] 8 => array:8 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0045" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Education \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.74e-11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.492 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MOCA score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.26e-34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MMSE score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.54e-24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BDNF pg/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12e-15 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3647223.png" ] ] ] ] "descripcion" => array:1 [ "en" => "p values of variables analyzed." ] ] 9 => array:8 [ "identificador" => "f0035" "etiqueta" => "Supplementary figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "mmc1.jpeg" "Alto" => 1264 "Ancho" => 1575 "Tamanyo" => 123624 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0050" "detalle" => "Supplementary figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mean BDNF pg/mL values by gender in cases group" ] ] 10 => array:8 [ "identificador" => "f0040" "etiqueta" => "Supplementary figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "mmc2.jpeg" "Alto" => 1178 "Ancho" => 1575 "Tamanyo" => 83065 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0055" "detalle" => "Supplementary figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mean BDNF pg/mL values by education category in cases" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Nations U, of Economic D, Affairs S, Division P. World Population Ageing 2019: Highlights." ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of cognition using surveys and neuropsychological assessment: the Health and Retirement Study and the Aging, Demographics, and Memory Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E.M. Crimmins" 1 => "J.K. Kim" 2 => "K.M. Langa" 3 => "D.R. Weir" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Gerontol B Psychol Sci Soc Sci" "fecha" => "2011" "volumen" => "66" "numero" => "Suppl 1" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mild cognitive impairment and its management in older people" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.A. Eshkoor" 1 => "T.A. Hamid" 2 => "C.Y. Mun" 3 => "C.K. Ng" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "Clinical Interventions in Aging" "paginaInicial" => "687" "paginaFinal" => "693" "serieVolumen" => "Vol. 10" "serieFecha" => "2015" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bb0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stage-Specific Behavioral, Cognitive, and In Vivo Changes in Community Residing Subjects With Age-Associated Memory Impairment and Primary Degenerative Dementia of the Alzheimer Type" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Reisberg" 1 => "S.H. 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Relación entre el factor neurotrofico derivado del cerebro y deterioro cognitivo de leve a moderado en adultos mayores mexicanos

E. Rico-Fernándeza,

,1, C.A. Reyes-Hernandezb,2, M.P. Rico-Fernándezc,3, F.J. García-Alvaradod,4, H.A. Delgado-Aguirred,5

a Neurology, Clinical Neurophysiology, Instituto Mexicano del Seguro Social, Hospital de pediatría Silvestre Frenk Freund, Centro Médico Nacional Siglo XXI, Ciudad de México, Mexico

b Internal Medicine, Infectious Diseases, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Ciudad de México, Mexico

c Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Madero, Mexico

d Health Education and Research Department, Instituto Mexicano del Seguro Social, Unidad Médica de Alta Especialidad (UMAE) N°71, Torreón, Coahuila, Mexico

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          "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Distribution of BDNF &#40;pg&#47;ml&#41; in the general study population&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Justification</span><p id="p0005" class="elsevierStylePara elsevierViewall">Cognitive impairment is a high-risk condition for the onset of dementia&#44; developed dependency&#44; functional impairment&#44; and a predictor of mortality&#44; conditioning a burden for the primary caregiver&#46; The brain-derived neurotrophic factor is a regulator of synaptic plasticity&#44; neuronal survival&#44; and differentiation&#44; including a critical molecular target for drug development in neurological disorders&#46; There are no studies on BDNF and mild to moderate cognitive impairment in the Mexican population&#46; Therefore&#44; it is essential to explore early expression biomarkers that contribute to early detection and benefit the prognostic outlook of these patients&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Introduction</span><p id="p0010" class="elsevierStylePara elsevierViewall">According to World Population Prospects 2019 &#40;United Nations&#44; 2019&#41;&#44; by 2050&#44; 1 in 6 people in the world will be over the age of 65&#44; up from 1 in 11 in 2019<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>&#46; This rapid demographic aging will increase the prevalence of disease and disabilities&#44; with an expected particular emphasis on the impairment of cognitive functions<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">Cognitive deficit is a syndrome characterized by a decline in cognitive functions more significant than expected for age and individual educational level&#44; which does not significantly interfere with activities of daily living<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">The term cognitive impairment was introduced in the late 1980s by Reisberg et al&#46; &#40;1988&#41; to characterize people in this intermediate stage<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a>&#46; Petersen et al&#46; &#40;1999&#41; further developed the concept by proposing criteria based on an observational study of aging<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>&#46; In 2003&#44; derived from the symposium&#44; the international standards for moderate cognitive impairment were published<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Cognitive impairment and dementia represent conditions that affect the quality of life of the elderly population and determine a greater use of health services&#46; Cognitive impairment constitutes a high-risk condition for the appearance of dementia&#44; with a probability of developing it of 10&#8211;15&#37; per year&#44; compared to healthy controls&#44; where it is 1&#8211;2&#37;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">Dementia is one of the determinants for the development of dependency and functional deterioration in adults over 75&#8239;years of age&#44; with the consequent burden for the primary caregiver&#44; in addition to being a strong predictor of mortality&#44; with a risk of 2&#8211;3 times greater when compared to other chronic diseases that reduce life expectancy<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">Brain-derived neurotrophic factor &#40;BDNF&#41; is one of the neurotrophic factors involved in the differentiation<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>&#44; maturation<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a>&#44; and survival of neurons in the nervous system<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a>&#46; It shows a neuroprotective effect under adverse conditions&#44; such as glutamatergic stimulation&#44; cerebral ischemia&#44; hypoglycemia&#44; and neurotoxicity<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a>&#46; BDNF stimulates and controls neurogenesis<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">BDNF contains 11 exons&#46; It encompasses approximately 70&#8239;kB and is located on chromosome 11p<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>&#44; which consists of a mature isoform of 118 amino acids that specifically binds to the tropomyosin kinase B receptor&#44; increasing the excitatory synapse and inhibiting GABAergic neuronal synapse<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a>&#46; BDNF protein and mRNA have been identified in most brain areas&#44; including the olfactory bulb&#44; cortex&#44; hippocampus&#44; basal forebrain&#44; midbrain&#44; hypothalamus&#44; brainstem&#44; and spinal cord&#46; A critical role in regulating plastic changes in the adult brain&#44; including regulation of NMDAR transport&#44; phosphorylation&#44; and expression levels&#46; BDNF has been postulated to be an essential part of the cellular mechanism for memory formation and maintenance by promoting synaptic consolidation<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall">BDNF plays a vital role in cognitive alterations related to hippocampal atrophy and structures involved in memory&#46; Low serum levels have been associated with reduced Folstein Mini-Mental State Examination &#40;MMSE&#41; scores in patients with dementia&#46; Komulainen et al&#46; &#40;2008&#41; found that BDNF levels were associated with cognitive function in older women&#44; suggesting that plasma BDNF may be a clinically relevant biomarker<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a>&#46; Shimada et al&#46; &#40;2014&#41; reported lower levels of BDNF associated with lower scores and moderate cognitive impairment<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">This study aims to compare BNDF serum levels in a Mexican adult population with mild to moderate cognitive impairment and controls&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Methods</span><p id="p0055" class="elsevierStylePara elsevierViewall">Case&#8211;control study in patients diagnosed with mild to moderate cognitive impairment and patients without cognitive impairment as a control group in a highly specialized hospital in northwestern Mexico&#46;</p><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Study population</span><p id="p0060" class="elsevierStylePara elsevierViewall">Our study evaluated 191 people who were users of the Instituto Mexicano del Seguro Social &#40;IMSS&#41; in the period from February 2020 to February 2021&#46; To be included&#44; each participant was 55&#8239;years old or older at the time of the study and did not have participated in other studies&#46; Patients with current severe medical conditions &#40;e&#46;g&#46;&#44; recent myocardial infarction&#44; decompensated heart failure&#44; metabolic imbalance&#44; hydroelectrolytic disturbances&#41;&#44; neurological or psychiatric history &#40;e&#46;g&#46;&#44; cerebrovascular accident&#44; Alzheimer&#39;s disease&#44; schizophrenia&#44; mental disorder&#44; bipolar&#44; depression&#41; were excluded&#46; Patients who do not sign an informed consent letter or with missing data were excluded&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Cognitive impairment criteria and cognitive function tests</span><p id="p0065" class="elsevierStylePara elsevierViewall">We defined cognitive impairment based on previous studies &#40;Petersen et al&#46;&#44; 2014&#41;&#44; using the following criteria&#58; &#40;1&#41; self-reported or family-reported memory complaint&#59; &#40;2&#41; objective memory impairment &#40;indicated by an age-adjusted score of at least 1&#46;5 SD below the lower reference limit of tests used for neuropsychological assessments&#41;&#59; &#40;3&#41; no evidence of functional dependency&#59; &#40;4&#41; exclusion of people with criteria for dementia&#46;<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="li0005"><span class="elsevierStyleLabel">1&#46;</span><p id="p0070" class="elsevierStylePara elsevierViewall">Screening for cognitive impairment includes a standardized face-to-face interview to collect sociodemographic&#44; anthropometric&#44; medical history&#44; and functional status data&#44; along with tests of cognitive function using the Mini-Mental State Examination &#40;MMSE&#174;&#41; and Montreal Cognitive Assessment &#40;MoCA&#174;&#41;&#44; scales are validated in the Mexican population&#59;<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> both scales simultaneously&#44; considering the patient&#39;s comfort and compliance to continue with the evaluations&#46;</p></li></ul></p><p id="p0075" class="elsevierStylePara elsevierViewall">The study complied with the principles of the Declaration of Helsinki&#46; All participants gave their informed consent to participate in this study&#59; the study protocol was authorized with the registration number &#40;R-2020-1002-010&#41; by the ethics committee in health research of the High Specialty Medical Unit &#40;IMSS- UMAE No&#46; 71&#41;&#44; Torreon&#44; Coahuila&#44; Mexico&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Assessment of cognitive impairment</span><p id="p0080" class="elsevierStylePara elsevierViewall">The Folstein Mini-Mental State &#40;MMSE&#174;&#41; and Montreal Cognitive Assessment &#40;MoCA&#174;&#41; scales were applied to determine the cognitive function and screening for cognitive impairment&#46; Standard cut-off points for MMSE&#174; normal &#40;MMSE 24&#8211;30&#41;&#44; mild &#40;20&#8211;23&#41;&#44; moderate &#40;MMSE 10&#8211;19&#41;&#44; and severe &#40;MMSE &#60;<span class="elsevierStyleHsp" style=""></span>9&#41; were used based on previous studies &#40;Benoit et al&#46;&#44; 2020&#41;&#46; For MoCA&#174;&#44; the following cut-off points were used for normal &#40;MoCA &#62;<span class="elsevierStyleHsp" style=""></span>26&#41;&#44; mild &#40;MoCA 18&#8211;25&#41;&#44; moderate &#40;MoCA 10&#8211;17&#41;&#44; and severe &#40;MoCA &#60;<span class="elsevierStyleHsp" style=""></span>10&#41; classification according to provider recommendations&#46;</p><p id="p0085" class="elsevierStylePara elsevierViewall">Based on the scores obtained&#44; the participants were classified into 2 large groups&#58; those with cognitive impairment &#40;cases&#41; and participants without cognitive impairment &#40;controls&#41;&#46; The flow of participants can be seen in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Sample collection</span><p id="p0090" class="elsevierStylePara elsevierViewall">Participants were instructed to attend the sample collection after fasting for 8&#8239;h&#46; The blood sample was obtained by venipuncture&#44; with a pool in a BD Vacutainer&#174; SST&#8482; tube of 6&#8239;mL whole blood&#46; The model coagulation was at room temperature for 30&#8239;min and subsequent centrifugation at 2500&#8239;rpm&#47;min for 20&#8239;min&#59; the serum was stored at a temperature of &#8722;<span class="elsevierStyleHsp" style=""></span>80&#8239;&#176;C for further analysis&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Quantitative determination of serum levels of BDNF</span><p id="p0095" class="elsevierStylePara elsevierViewall">Quantitative determination of BDNF levels in serum was analyzed using a commercial kit &#40;BDNF Human ELISA kit&#44; Aviscera Biosciences&#44; Santa Clara&#44; CA&#44; USA&#41; following the manufacturer&#39;s instructions&#46; Serum samples were diluted in polypropylene test tubes 40 times &#40;10&#8239;&#956;L sample<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>390&#8239;&#956;L dilution buffer&#41;&#46; Samples were added to the 96-well flat bottom plate and then shaken for 2&#8239;h at room temperature&#46; Subsequently&#44; after washing 4 times&#44; a detection antibody was added to each well&#44; and the plates were incubated for 2&#8239;h under constant agitation at room temperature&#46; After another washing step&#44; horseradish peroxidase-conjugated streptavidin was added&#44; and the plates were incubated for 60&#8239;min at room temperature&#44; protected from light&#46; Unbound streptavidin was discarded&#44; and TMB substrate solution was added&#46; The reaction was stopped 15&#8239;min later&#46; Optical density was measured in a microplate reader &#40;Stat Fax&#174; 4700 Awareness Technology&#44; USA&#41; at a 450<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#8239;nm wavelength proportional to the BDNF concentration&#46; The intra- and inter-assay variations of BDNF were less than 9&#37;&#46; BDNF concentrations were determined according to the BDNF standard curve&#46; All assays were duplicated&#44; and results were expressed in pg&#47;ml&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Statistical analysis</span><p id="p0100" class="elsevierStylePara elsevierViewall">The Chi-square homogeneity test was used to compare cognitive impairment with the categorical variables of the control group and cases&#46; Student&#39;s <span class="elsevierStyleItalic">t</span>-test was applied to compare cognitive impairment with BDNF levels with normal distribution or Mann&#8211;Whitney&#39;s <span class="elsevierStyleItalic">U</span> test for non-normal distribution&#46; Differences in serum BDNF concentrations were performed by one-way analysis of variance &#40;ANOVA&#41; in both sexes&#46; All statistical comparisons were performed at a significance level of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#44; and all statistical and data management calculations were performed using the scikitlearn&#174;&#44; scipy&#174;&#44; and pandas&#174; Library Software Package in the scikitlearn&#174;&#44; scipy&#174;&#44; and pandas&#174; programming language Python&#174;&#46;</p></span></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Results</span><p id="p0105" class="elsevierStylePara elsevierViewall">One hundred ninety-one patients were included in the study&#59; the main characteristics of the participants are in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#46; The mean age of the participants was 65&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;15&#46; The average schooling was 10&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;55&#8239;years&#46; Eighty-one women &#40;42&#37;&#41; and 110 men &#40;58&#37;&#41; were included in the study&#46; The average score of the participants in general in the MMSE&#174; instrument was 25&#46;67<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;63&#44; and using the MoCA&#174; tool&#44; 24&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;51&#46;</p><p id="p0110" class="elsevierStylePara elsevierViewall">The mean age for the case group was 67&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;43&#44; and for the control group&#44; it was 63&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;38&#46; Regarding gender&#44; in the case group&#44; there are 53 men &#40;52&#37;&#41; and 49 women &#40;48&#37;&#41;&#59; in the control group&#44; there are 57 men &#40;64&#37;&#41; and 32 women &#40;36&#37;&#41;&#46; The number of years of study in the case group was 8&#46;98<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>3&#46;96&#59; for the control group&#44; it was 13&#46;15<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>4&#46;17&#46;</p><p id="p0115" class="elsevierStylePara elsevierViewall">Regarding the score obtained by the MoCA&#174; instrument in the group of cases&#44; 94 patients were classified as having a mild cognitive impairment &#40;92&#46;1&#37;&#41;&#59; 8 patients were classified as having a moderate cognitive impairment &#40;7&#46;8&#37;&#41;&#44; and no patients were classified as having severe cognitive impairment&#46; Using the MMSE&#174; instrument&#44; 94 patients with mild cognitive impairment &#40;92&#46;1&#37;&#41;&#44; 6 with moderate cognitive impairment &#40;5&#46;8&#37;&#41;&#44; and 2 patients with severe cognitive impairment &#40;1&#46;9&#37;&#41; were classified from the case group&#46; The mean serum concentration of BDNF in the case group was 277&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>75&#46;09 vs&#46; the control group&#44; where the concentration was 354&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>66&#46;06&#8239;pg&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#44; mean BDNF levels were higher in females&#46; Likewise&#44; we can observe in <a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a> that according to the level of schooling&#44; the level of BDNF increases&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0125" class="elsevierStylePara elsevierViewall">BDNF concentrations varied according to the classification of cognitive impairment based on the MMSE&#174; and MoCA&#174; tests &#40;<a class="elsevierStyleCrossRefs" href="#f0015">Figs&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="f0020"></elsevierMultimedia><p id="p0130" class="elsevierStylePara elsevierViewall">The correlation was made between the variables with the serum level of BDNF&#44; shown in <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a><span class="elsevierStyleBold">&#46;</span> where it was found that there is a correlation between BDNF and cardiovascular diseases&#44; years of schooling&#44; MMSE score&#44; and MOCA score&#46; Moreover&#44; the general distribution of the BDNF marker shows a normal distribution curve &#40;<a class="elsevierStyleCrossRef" href="#f0025">Fig&#46; 5</a>&#41;&#44; which is why the ANOVA F value analysis is performed &#40;<a class="elsevierStyleCrossRef" href="#f0030">Fig&#46; 6</a>&#41;&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia><elsevierMultimedia ident="f0030"></elsevierMultimedia><p id="p0135" class="elsevierStylePara elsevierViewall">The statistical analysis presented in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a> and the accompanying ANOVA F value in <a class="elsevierStyleCrossRef" href="#f0030">Fig&#46; 6</a> is a comprehensive view of the significance of the variables present in our study&#46; The <span class="elsevierStyleItalic">p</span>-values in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a> reveal that &#8216;Education&#8217;&#44; &#8216;MOCA score&#8217;&#44; &#8216;MMSE score&#8217;&#44; and &#8216;BDNF pg&#47;ml&#8217; with values below 0&#46;05&#44; indicating significant statistical relevance&#46; This is supported by the ANOVA F-value analysis in <a class="elsevierStyleCrossRef" href="#f0030">Fig&#46; 6</a>&#44; where the corresponding F-values for these variables are markedly high&#44; with the &#8216;MOCA score&#8217; peaking at 41&#46;62&#44; highlighting its substantial influence&#46; Conversely&#44; &#8216;BMI&#8217; demonstrates a <span class="elsevierStyleItalic">p</span>-value of 0&#46;492&#44; paired with a relatively low F-value&#44; indicating that it does not have a significant association&#46; The alignment of low <span class="elsevierStyleItalic">p</span>-values with high F-values confirms the robustness of the variables&#39; impact&#44; underscoring their importance in the research findings&#46; These statistical measures collectively highlight the variables most critical to the study&#39;s conclusions and those that may be considered less influential&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0125">Discussion</span><p id="p0140" class="elsevierStylePara elsevierViewall">Our study aimed to compare serum BDNF levels in Mexican patients with mild&#8211;moderate cognitive impairment and a control group from a high-specialty hospital&#46;</p><p id="p0145" class="elsevierStylePara elsevierViewall">The number of people worldwide with cognitive impairment in 2000 was approximately 20 million&#59; this figure will reach 81&#46;1 million in 2040&#46; Several studies have shown that neurotrophic factors such as BDNF are involved in the pathophysiology of neurodegenerative diseases&#46; Higher serum BDNF levels are associated with better MoCA&#174; &#47; MMSE&#174; test performance&#46;</p><p id="p0150" class="elsevierStylePara elsevierViewall">In the present study&#44; we found that patients with moderate&#44; mild cognitive impairment determined by the MoCA&#174; &#47; MMSE&#174; score have a lower serum level of BDNF than subjects with normal scores in these instruments&#46; The mean serum concentration of BDNF in the case group was 277&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>75&#46;09 vs&#46; the control group with 354&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>66&#46;06&#8239;pg&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><p id="p0155" class="elsevierStylePara elsevierViewall">Laske et al&#46; &#40;2006&#41; found that early-stage patients with MMSE scores &#8805;<span class="elsevierStyleHsp" style=""></span>21 &#40;mean 25&#46;5&#41; had significantly higher serum BDNF levels compared with late-stage patients with MMSE scores &#60;<span class="elsevierStyleHsp" style=""></span>21 &#40;mean 25&#46;5&#41;&#46; and age-matched healthy controls&#46; The mean age of their case group was 71&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;0&#44; and the control group was 70&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;4&#46; The mean MMSE&#174; score for the case group was 19&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;0&#44; and the control group was 29&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2&#46; It was found that in the control group&#44; the mean concentration of BDNF was 20&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2&#8239;ng&#47;ml&#59; in the initial stages of the disease&#44; it was 25&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;1&#8239;ng&#47;ml vs&#46; the group in the final stages&#44; where the mean concentration was 17&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4&#8239;ng&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; There was a correlation between the serum level of BDNF and the score obtained in the MMSE&#174; instrument &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;486&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46;</p><p id="p0160" class="elsevierStylePara elsevierViewall">Yu et al&#46; &#40;2008&#41; looked for an association between serum BDNF levels and patients with mild cognitive impairment&#46; They recruited 99 patients with a previous diagnosis of mild cognitive impairment and 99 healthy patients&#46; Serum levels of BDNF were determined&#46; They reported in their study that serum BDNF concentrations in patients with mild cognitive impairment &#40;&#91;interquartile range&#93;&#61;4&#46;37 &#91;2&#46;35&#8211;6&#46;40&#93; ng&#47;ml&#41; were significantly lower than in healthy controls &#40;4&#46;98 &#91;3&#46;50&#8211;7&#46;33&#93; ng&#47;ml&#41; &#40;z<span class="elsevierStyleHsp" style=""></span>&#61;&#8722;2&#46;449&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;014&#41;&#46; with a positive correlation between BDNF and delayed memory scores on the auditory verbal learning test&#44; reflecting episodic memory &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;264&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;008&#41;&#46; This study suggests that reduced levels of BDNF may play a role in the pathophysiology of mild cognitive impairment&#46;</p><p id="p0165" class="elsevierStylePara elsevierViewall">Murillo-Ortiz et al&#46; &#40;2016&#41; in their study included 40 patients with type 2 diabetes mellitus &#40;mean age 51&#46;88<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;81&#41; and 40 healthy patients &#40;mean age 42&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;87&#41;&#46; MMSE&#174; was performed to classify them into 2 groups&#58; with or without cognitive impairment&#46; The mean score using the MMSE&#174; instrument was 20&#46;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;15 for the case group and 25&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;50 for the control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; BDNF determination was performed in both groups&#44; finding a statistically significant difference &#40;31&#46;55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;24 vs&#46; 43&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;05&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;005&#41;&#46;</p><p id="p0170" class="elsevierStylePara elsevierViewall">The mentioned authors&#39; results support our research findings&#44; showing that lower scores in instruments such as MMSE&#174; and MoCA&#174; were associated with lower serum concentrations of BDNF&#46; These studies use MMSE&#174; to measure cognitive status and classify patients with or without cognitive impairment&#44; which is consistent with our research methodology&#46; They report meaning MMSE&#174; scores of 20&#46;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;15 for the case group and 25&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;50 for the control group&#46; In our study&#44; the mean score for the case group was 21&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;06&#59; for the control group&#44; it was 28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;45&#46; The serum concentrations of BDNF were lower in the case group vs&#46; the control group&#44; showing a difference with statistical significance&#46; These results agree with what was previously reported&#46; There is a certain degree of variability between their groups&#39; scores and serum BDNF concentrations concerning ours&#44; but they generally present the same trend&#46;</p><p id="p0175" class="elsevierStylePara elsevierViewall">As secondary results&#44; it can be observed that there is a correlation between BDNF and cardiovascular diseases&#44; schooling in years&#44; MMSE&#174; score&#44; and MOCA&#174; score&#46; Moreover&#44; the <span class="elsevierStyleItalic">p</span>-value and ANOVA F value analysis confirm these variables&#39; importance and impact on the BDNF levels&#46;</p><p id="p0180" class="elsevierStylePara elsevierViewall">There is disagreement between the different publications on BDNF levels concerning gender&#46; Some publications suggest that estrogens have a positive regulatory effect on BDNF expression and signaling&#46; However&#44; these observations were generated from fragmented studies&#44; which were not primarily designed to examine the tissue distribution of BDNF in different sexes<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a>&#46; In our study&#44; estrogen levels were not quantified&#44; so we cannot infer this relationship&#46;</p><p id="p0185" class="elsevierStylePara elsevierViewall">Hashimoto &#40;2016&#41; conducted a study to determine if there is a difference between serum levels of BDNF based on ethnic origin&#59; according to the study by Yoshida &#40;2012&#41;&#44; the Japanese population shows a mean level of BDNF of 23&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;90&#8239;ng&#47;ml&#59; Sodersten &#40;2014&#41; reported 30&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;2&#8239;ng&#47;ml for the Swedish people and Levin &#40;2015&#41; for the Jewish population 14&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;9&#8239;ng&#47;ml&#46; Therefore&#44; there is evidence that the concentration varies according to ethnic origin&#46;</p><p id="p0190" class="elsevierStylePara elsevierViewall">Shimada et al&#46; &#40;2014&#41; reported that serum BDNF levels are lower in patients with mild cognitive impairment &#40;OR&#44; 95&#37;&#44; CI 1&#46;41&#44; 1&#46;00&#8211;1&#46;99&#41;&#46; Patients older than 65&#8239;years were included in this study&#44; and those with established neurological diseases were excluded&#46; They found that BDNF levels varied by gender for men &#40;20&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;6&#8239;ng&#47;ml&#41; and women &#40;21&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2&#8239;ng&#47;ml&#59; <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;162&#44; df<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4394&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;031&#41;&#46; In both groups&#44; serum BDNF levels were associated with age &#40;&#946;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;123&#44; <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#46;750&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Serum levels of BDNF were associated with a decrease in memory and calculation tests &#40;&#946;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#44; <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;958&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; Finding that age presented an OR for mild cognitive impairment of 1&#46;00 &#40;95&#37; CI 0&#46;99&#8211;1&#46;02&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;977&#41;&#44; gender of 0&#46;85 &#40;95&#37; CI 0&#46;71&#8211;1&#46;00&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;051&#41;&#44; education 0&#46;82 &#40;95&#37; CI 0&#46;79&#8211;0&#46;85&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;&#60;&#46;001&#41; and type 2 diabetes mellitus of 1&#46;04 &#40;95&#37; CI 0&#46;82&#8211;1&#46;31&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;23&#41;&#46;</p><p id="p0195" class="elsevierStylePara elsevierViewall">Villela-Nunes et al&#46; &#40;2018&#41; included 80 deceased participants with a diagnosis of dementia and depression in their study&#44; compared with a control group of 80 deceased patients without these diagnoses&#46; Patients with traumatic death&#44; neoplasms&#44; severe systemic diseases&#44; and unknown causes of death were excluded&#46; The mean age for the case group was 73&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;3&#44; for the control group 74&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;1 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;58&#41;&#44; in the case group&#44; there were 15 patients with cardiovascular disease &#40;18&#46;75&#37;&#41;&#44; and in the case group 14 patients with this condition &#40;17&#46;5&#37;&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;84&#41;&#46; BDNF determination was performed in the prefrontal cortex&#44; reporting lower levels in the case group vs&#46; the control group &#40;&#223;<span class="elsevierStyleHsp" style=""></span>&#61;-0&#46;106&#44; 95&#37;CI<span class="elsevierStyleHsp" style=""></span>&#61;&#8722;0&#46;204&#59; &#8722;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;034&#41;&#46; They did not note differences in other variables&#44; such as diabetes mellitus&#44; cardiovascular diseases&#44; and depression&#46;</p><p id="p0200" class="elsevierStylePara elsevierViewall">Concordance is found between the characteristics of our population and the previously reported studies&#44; except for cardiovascular disease&#44; since 56&#37; of our participants declared themselves with this diagnosis&#46; According to national statistics in Mexico&#44; it is estimated that 70&#46;3&#37; of the adult population has at least one cardiovascular disease&#46; The prevalence of obesity in the country in the adult population is 33&#46;6&#37;&#44; according to ENSANUT data&#59; in our study&#44; a majority of 26&#37; was reported&#46;</p><p id="p0205" class="elsevierStylePara elsevierViewall">A difference can be observed between the mean concentration of BDNF in our population and that of other studies&#46; The enormous heterogeneity of published serum BDNF levels is mainly due to methodological issues&#44; which need to be more noticed in quite a few publications &#40;e&#46;g&#46;&#44; sample storage conditions&#44; effects of repeated freeze&#8211;thaw cycles&#44; and the different ELISA kits used&#41;&#46;</p><p id="p0210" class="elsevierStylePara elsevierViewall">The strengths of the present study include the large sample size&#44; as we matched the size of previous studies&#8212;comprehensive measurement of cognitive function by implementing both widely validated tests in the Mexican population&#46; The analysis of other variables that could affect the result&#44; such as diabetes mellitus and cardiovascular diseases&#44; is closely correlated with mild cognitive impairment&#8212;having rigorous exclusion criteria that could influence the outcome&#46; Blood samples were taken at times reported in other studies to avoid the influence of circadian cycles on the result&#46;</p><p id="p0215" class="elsevierStylePara elsevierViewall">The limitations of the present study include that it is a cross-sectional study&#44; which did not have a database&#44; and limited blinding since the same person who applied the tests to measure cognitive abilities was involved in processing samples and results&#46; The heterogeneity of our population with a medical affiliation is evident&#44; which limited the power to match the groups&#44; showing in the clinical characteristics a tendency of the group of cases to suffer more cardiovascular diseases&#46;</p><p id="p0220" class="elsevierStylePara elsevierViewall">Although our study was population-based&#44; further prospective research is needed to validate the use of serum BDNF levels to discriminate the risk of cognitive decline&#46;</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0130">Conclusion</span><p id="p0225" class="elsevierStylePara elsevierViewall">In patients from the study population of cases and controls&#44; utilizing the MoCA&#174; and MMSE&#174; screening test and serum marker analysis BDNF&#44; there is a significant difference between control groups and patients with cognitive impairment in any of its clinical stages&#46;</p><p id="p0230" class="elsevierStylePara elsevierViewall">The mean serum concentration of BDNF in the case group was 277&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>75&#46;09 vs&#46; the control group of 354&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>66&#46;06&#8239;pg&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><p id="p0235" class="elsevierStylePara elsevierViewall">The level of BDNF was found in both groups&#44; with a lower concentration in the male gender compared to the female gender&#44; as well as a higher level of biomarker related to schooling &#40;Master&#39;s degree&#41; in both groups&#46;</p><p id="p0240" class="elsevierStylePara elsevierViewextended">The following are the supplementary data related to this article&#46;<elsevierMultimedia ident="f0035"></elsevierMultimedia><elsevierMultimedia ident="f0040"></elsevierMultimedia></p><p id="p0245" class="elsevierStylePara elsevierViewcompact-standard">Supplementary data to this article can be found online at <a href="https://doi.org/10.1016/j.neurop.2024.100158">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;neurop&#46;2024&#46;100158</a>&#46;</p></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0135">Financial Support</span><p id="p0250" class="elsevierStylePara elsevierViewall">The researchers have yet to receive financial support for this article&#39;s research&#44; authorship&#44; and publication&#46;</p></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0140">Approval by the Ethics Committee</span><p id="p0255" class="elsevierStylePara elsevierViewall">Registration number R-2020-1002-010&#46;</p></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0145">Author contributions</span><p id="p0260" class="elsevierStylePara elsevierViewall">Study design and conception by ER&#44; CA&#44; HA&#44; FJ&#44; and MP&#59; Experiments were performed by ER&#44; CA&#44; HA&#44; FJ&#44; and MP&#59; and Data analysis by MP&#44; ER&#44; and CA&#46; All authors contributed to the writing and review&#46;</p></span></span>"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Background</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Mild&#8211;moderate cognitive impairment is a frequent pathology in the adult population&#46; It is important to explore early expression biomarkers that contribute to early detection and benefit the prognostic outlook&#46; Brain-derived neurotrophic factor &#40;BDNF&#41; is an essential regulator of synaptic plasticity&#44; neuronal survival&#44; and differentiation&#44; and even a critical molecular target for drug development in neurological disorders&#46; It is crucial to carry out studies in the early stages that better clarify the landscape of BDNF&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Objective</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">To compare the serum levels of BDNF in healthy adult patients and those with mild to moderate cognitive impairment&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Materials and methods</span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">A casecontrol study in patients over 55-&#8239;years with cognitive impairment&#44; obtained by the MMSE&#174; and MoCA&#174; screening scales&#46; A total of 191 patients&#44; 102 patients with cognitive impairment &#40;cases&#41; and 89 healthy ones &#40;controls&#41; participated in the study&#46; Blood samples were collected to obtain serum&#44; with the determination of BDNF concentrations&#46; For differences in BDNF concentrations&#44; a one-way analysis of variance was used&#46; The significance level of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Results</span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">The mean serum concentration of BDNF in the case group was 277&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>75&#46;09 vs&#46; the control group&#44; where the concentration was 354&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>66&#46;06&#8239;pg&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p></span> <span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Conclusions</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">There is an association between decreased BDNF levels and mild and moderate cognitive impairment in our study population&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Fundamento</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">El deterioro cognitivo leve-moderado es una patolog&#237;a frecuente en la poblaci&#243;n adulta mayor&#46; Es importante explorar biomarcadores de expresi&#243;n temprana que contribuyan a la detecci&#243;n temprana y beneficien el pron&#243;stico&#46; El factor neurotr&#243;fico derivado del cerebro &#40;BDNF&#41; es un regulador esencial de la plasticidad sin&#225;ptica&#44; la supervivencia y la diferenciaci&#243;n neuronal e incluso un objetivo molecular cr&#237;tico para el desarrollo de f&#225;rmacos en trastornos neurol&#243;gicos&#46; Es fundamental realizar estudios en las primeras etapas que aclaren mejor el panorama del BDNF&#46;</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Objetivo</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">Comparar los niveles s&#233;ricos de BDNF en pacientes adultos sanos y aquellos con deterioro cognitivo leve a moderado&#46;</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Materiales y m&#233;todos</span><p id="sp0085" class="elsevierStyleSimplePara elsevierViewall">Estudio de casos y controles en pacientes mayores de 55 a&#241;os con deterioro cognitivo&#44; obtenidos mediante las escalas de MMSE&#174; y MoCA&#174;&#46; Participaron en el estudio un total de 191 pacientes&#44; 102 pacientes con deterioro cognitivo &#40;casos&#41; y 89 sanos &#40;controles&#41;&#46; Se recogieron muestras de sangre para obtener suero&#44; con determinaci&#243;n de concentraciones de BDNF&#46; Para las diferencias en las concentraciones de BDNF&#44; se utiliz&#243; un an&#225;lisis de varianza unidireccional ANOVA&#46; El nivel de significancia de p&#8239;&#60;&#8239;0&#44;05&#46;</p></span> <span id="as0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Resultados</span><p id="sp0090" class="elsevierStyleSimplePara elsevierViewall">La concentraci&#243;n s&#233;rica media de BDNF en el grupo de casos fue de 277&#44;68&#8239;&#177;&#8239;75&#44;09 vs&#46; el grupo control&#44; donde la concentraci&#243;n fue de 354&#44;97&#8239;&#177;&#8239;66&#44;06&#8239;pg&#46; &#47;mL &#40;P&#8239;&#61;&#8239;0&#44;001&#41;&#46;</p></span> <span id="as0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Conclusiones</span><p id="sp0095" class="elsevierStyleSimplePara elsevierViewall">existe asociaci&#243;n entre niveles disminuidos de BDNF y deterioro cognitivo leve y moderado en nuestra poblaci&#243;n de estudio&#46;</p></span>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Measure</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; years&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#46;50 &#40;8&#46;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#46;79 &#40;7&#46;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Education&#44; years&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;98 &#40;3&#46;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;15 &#40;4&#46;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male sex&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MMSE&#174; score &#40;0&#8211;30&#41; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;46 &#40;3&#46;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;20 &#40;1&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MoCA&#174; score &#40;0&#8211;30&#41; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#46;92 &#40;3&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;10 &#40;1&#46;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertension&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heart disease&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;88 &#40;3&#46;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;26 &#40;3&#46;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal weight &#40;BMI &#60;<span class="elsevierStyleHsp" style=""></span>25&#41; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Overweight &#40;BMI 25&#8211;30&#41; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obesity &#40;BMI &#62;<span class="elsevierStyleHsp" style=""></span>30&#41; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BDNF expression&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">277&#46;68 &#40;75&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">354&#46;97 &#40;66&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Correlation of numerical variables concerning BDNF &#40;pg&#47;ml&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medical and demographic variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Cardiovascular diseases&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;<span class="elsevierStyleHsp" style=""></span>0&#46;275441&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&#8722;<span class="elsevierStyleHsp" style=""></span>0&#46;116012&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Arterial hypertension&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&#8722;<span class="elsevierStyleHsp" style=""></span>0&#46;072353&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Type II diabetes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;<span class="elsevierStyleHsp" style=""></span>0&#46;029303&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005882&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;049353&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Schooling &#40;Years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;21489&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MMSE&#174; score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;342508&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MoCA&#174; score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;426976&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BDNF &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Education&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;74e-11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;492&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MOCA score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;26e-34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MMSE score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;54e-24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BDNF pg&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;12e-15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                      "titulo" => "Assessment of cognition using surveys and neuropsychological assessment&#58; the Health and Retirement Study and the Aging&#44; Demographics&#44; and Memory Study"
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Article information

ISSN: 26670496
Original language: English

DOI:10.1016/j.neurop.2024.100158

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2024 October	22	14	36
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