The Spanish Society of Neurology (SEN) defines dementia as an acquired, persistent alteration in brain function that affects at least 2 cognitive spheres (memory, language, visuospatial function, executive functions, behaviour) to such an extent as to interfere with a person's daily activities without there being a change in his level of consciousness.1 This condition affects 4% of the population aged 60 and over worldwide, with few regional differences, although overall prevalence is higher in developed countries. Generally speaking, more than two-thirds of all subjects with dementia will be diagnosed with Alzheimer's disease (AD).2

Current treatments for AD have shown statistically significant levels of efficacy for improving cognitive function and almost all clinical manifestations of this condition. They are also cost-effective and improve patient and carer quality of life. Available guidelines therefore recommend beginning drug treatments as soon as AD is diagnosed.1,3,4 Nonetheless, this type of disorder often has insidious initial manifestations that make it difficult to distinguish from other entities. As a result, diagnosing AD in its earliest stages may be challenging.5 Late diagnosis of AD is accompanied by a late start for the specific drug treatment. However, mounting evidence shows that early treatment may optimise therapeutic benefits and delay cognitive decline.6 Doctors have therefore proposed initiatives for identifying the disease in its initial stages.7,8 In fact, in the area of AD studies, proposals to change AD diagnostic criteria in order to achieve early diagnosis have had considerable impact.9–14 Although it is commonly believed that cases are diagnosed in relatively advanced stages in clinical practice, we should stress that there is no reliable information about when AD is diagnosed in Spain. We proposed conducting EACE, a study of AD in specialist clinics, in order to collect this information. Its purpose was to describe patients’ stage of AD at the time of diagnosis in Spain, in specialist clinics able to indicate specific treatment for AD.

EACE is a multi-centre, observational cross-sectional study performed in Spanish specialist care clinics. The main purpose of the study is to describe the developmental stage at which patients with AD are referred to a specialist care centre for diagnosis. We also measure the time to provide care. Since the study is observational, it includes no clinical interventions.

The study was carried out by specialists in each of Spain's autonomous communities in which doctors consented to participate. Each specialist was asked to include the first 4 patients seen in the office or clinic between May and November 2009, with the following selection criteria: meeting NINCDS-ARDRA criteria for probable AD15 at that time and with no prior diagnosis of the disease; being able to take neuropsychological tests; and having a reliable informant who would be able to answer the study questions. It was assumed that patients who had previously been treated with specific drugs had already been diagnosed. They were excluded from the study, as were patients whose dementia stemmed from other causes (Parkinson's disease, hydrocephalus, stroke). Patients gave their informed consent to participate in the study according to good medical practice framework and the Declaration of Helsinki. The protocol was approved by the Clinical Research Ethics Committee at Hospital General Universitario, Elche.

Data were recorded in a single visit by the appropriate professional. The following variables were recorded for each case.

• 1.

  Sociodemographic variables: age, sex, education (years and level, classifying subjects as illiterate, functionally illiterate, primary studies, secondary studies, and higher education), household composition at symptom onset, and relationship with primary carer.

• 2.

  Family history, comorbidities, and concomitant treatments.

• 3.

  Clinic data: specialty referring the patient, specialty treating the patient, clinic location, clinic organisational level (general outpatient clinic, general or specific hospital department, dementia unit, other) and geographical data/demographics (location and city size, broken down as more than 500000, 100000 to 500000, and fewer than 100000 inhabitants.

• 4.

  Initial symptom of disease (impaired memory, language, behaviour, recognition, other).

• 5.

  Retrospective data for disease progression:

  • •

    Estimated date of symptom onset.

  • •

    Date of first visit.

  • •

    Date patient was referred to specialist.

  • •

    Estimated date of when patient started needing supervision.

  • •

    Date the specialist completed evaluation (diagnosis and inclusion in the study).

  • •

    Reasons for any delays in referral.

• 6.

  Description of the patient's cognitive, behavioural, and overall status, using:

  • •

    Mini-mental state examination (original16 and adapted versions17,18).

  • •

    Neuropsychiatric inventory (NPI).19,20

  • •

    Clinical dementia rating (CDR) scale.17,21

We estimated a sample size of 1600 cases in order to obtain valid estimates for scores on the scales listed above. We assumed a precision error at or below 25% and a 95% confidence interval (CI 95%) in a conservative scenario with a loss to follow-up of 5%. We analysed all patients who were included and met selection criteria. The sample was described with measures of central tendency and dispersion for quantitative variables and absolute and relative frequencies for qualitative variables, with their corresponding CI 95%. We also completed bivariate analyses to explore certain subgroups. Quantitative variables were evaluated using the Kolmogorov–Smirnov test; variables not meeting criteria for a normal distribution were measured using non-parametric methods. Statistical tests were bilateral and they employed a 5% significance level. SAS® software version 8.2 was used to complete all statistical analyses.

Results from the EACE study suggest that most patients with AD in Spain are diagnosed by a specialist when the disease is in a moderate stage. This is shown by both the mean raw MMSE score of 17.6 and by the fact that more than 70% of the cases have an MMSE score of less than 20 points. Early diagnosis is possible, and it has even occurred in our population in a low percentage of cases of patients with an MMSE of 24 or less, but such cases are far from common. Most cases show disease progression, given that they are more frequently diagnosed in moderate than in mild stages. A sizeable percentage is also diagnosed in severe stages in which the chances of altering the course of the disease are much lower.

In our sample, the overall profile with regard to neuropsychiatric symptoms is similar to that described in the literature for the AD stage of disease. This situation also confirms that patients’ disease has progressed considerably by the time of diagnosis, since these symptoms are less common in initial stages of AD.22 If our patients generally begin receiving treatment in moderate stages of the disease, it seems clear that there is considerable room for improvement in this area. AD patients should have access to a treatment plan that would be able to provide some degree of improvement in order to affect the course of the disease at all levels. Since a diagnosis is typically not reached until more advanced stages, we are missing many treatment opportunities and failing to take advantage of options that would improve the clinical status of numerous patients. Reaching a diagnosis at a relatively early stage of the disease is the key to making good use of treatment options.3,4,8,23–25 It seems there is no longer any debate regarding early diagnosis and the distinction between AD and mild cognitive impairment.26,27 As a result, much of the effort in current research is directed at achieving reliable diagnosis of AD in phases of cognitive impairment that are not too advanced.11,13

The time elapsed between estimated onset of symptoms and obtaining a specialist's diagnosis is more than 2 years (mean of 28.4 months). Although this figure is similar to those cited in other studies,28 it is probably less than the true time elapsed because it was estimated retrospectively by informants in every case. This total time to diagnosis includes different stages; the duration of each stage may be due fundamentally to different factors which may be affected specifically. To cite an example, the average time of nearly 11 months between symptom onset and the first visit to a primary care doctor is clearly due in part to poor recognition and awareness of those symptoms by carers and the general population. Awareness-raising campaigns may have a positive effect on this time factor. On the other hand, the average of 8.1 months that it takes for a case to be referred from primary care to a specialist may be reduced by implementing the right mechanisms for identifying patients and referring them to specialist care. We should also point out the disparity among time-to-care measurements in the sample (Table 2), reflecting healthcare variability throughout Spain. The specialist care level shows room for improvement, although this study did not measure how much improvement is needed. Changes should be applied to the management of complementary diagnostic tests (analyses and neuroimaging) if these tests are not available from the first visit to the specialist.

Regarding sociodemographic characteristics, it is important to stress the high percentage of functionally illiterate patients. This finding resembles results from other series completed in the same geographical area.29 On the other hand, it comes as no surprise that geriatric specialists care for older patients, or that institutionalised patients would also be older than the non-institutionalised. The fact that institutionalised patients are less frequently seen by neurologists than by geriatric specialists and psychiatrists probably reflects the fact that neurologists do not typically work in institutional homes.

It is also logical that patients seen by psychiatrists would have more neuropsychiatric symptoms, a somewhat poorer clinical condition, and be more likely to require antipsychotic drugs (data not shown), even though their mean age is no older than the rest of the population's. The differences between groups of patients cared for by different specialists do not reflect different care approaches. Instead, they can be explained by logical referral biases according to each specialty and the location where the care is provided.

There is a statistically significant difference between patient stages according to the size of the city in which they are treated. In smaller cities, impairment will be more pronounced. This is true on both the cognitive level (a lower average MMSE) and a behavioural level (higher NPI score). This tendency may be due to a number of causes. It may in fact correspond to the variable ‘demand for attention’, such that there may be more demand for care in urban settings, which could be due to better awareness of the disease. At the same time, demand corresponding to mild cases may be lower in more rural settings in which the patient may receive more support from those in his or her environment. Organisational phenomena may also be involved; there may be a difference in specialist availability in these areas, or one may simply find different referral or clinical practices among professionals in different areas.

The EACE study has some obvious limitations. First of all, there is a selection bias inherent to the study design. Because of its design, the study will underestimate care provided by specialist units and clinics, since these units provided only 4 cases, just as the general clinics did. It may also underestimate care in large cities. While the study represents the entire geographical territory, representation is not exactly population-based. This bias may be less important than it seems, however. Results are fairly homogeneous when they are considered by different subgroups, and the overall level of dispersion for the sample is similar to the level of dispersion of its subgroups. Because of study characteristics, the data for each section are occasionally incomplete. Some disease progression data are retrospective estimates, but they are supported by data obtained objectively: time of referral, and first primary care visit due to AD symptoms. Using MMSE as a tool to classify dementia severity may overestimate that severity in patients with a low educational level. However, we find it much more reliable than CDR, an instrument that is much less widely used in Spain. We also believe that many researchers lack training and familiarity with the CDR. The study has many obvious strengths as well: its large sample size and ample representation of healthcare professionals. In addition, the fact that the study's results are similar to those from other series lends it credibility, despite the biases listed above.

Regardless of the study's limitations, we feel that the healthcare situation it describes demonstrates that AD is not normally diagnosed in patients in mild stages of the disease. If we are to diagnose patients in less-evolved stages, we should re-examine awareness campaigns according to what we know now. A greater effort should also be made to coordinate between care levels and create care circuits and referral protocols that will help us achieve this goal. Furthermore, this goal is desirable for society at large, not only from a humanitarian viewpoint, but also in terms of cost-effectiveness. Providing care, support, and treatment to a group of patients that is seriously affected by a treatable disease is more than a social and ethical requirement; it will actually lower the costs generated by that disease.

The EACE study was financed by Pfizer España. Margarita González-Adalid is employed by Pfizer España. The other authors have no conflicts of interest to declare.