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Inicio Clínica e Investigación en Arteriosclerosis Estatinas y enfermedad de Alzheimer: ¿son concluyentes los estudios actuales?
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Vol. 17. Issue S1.
Hot topics en Arteriosclerosis
Pages 2-6 (May 2005)
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Vol. 17. Issue S1.
Hot topics en Arteriosclerosis
Pages 2-6 (May 2005)
Hot topics en arteriosclerosis
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Estatinas y enfermedad de Alzheimer: ¿son concluyentes los estudios actuales?
Statins and alzheimer's disease: are current studies conclusive?
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J.M. Mostaza
Corresponding author
jmostaza.hciii@salud.madrid.org

Correspondencia: Dr. J.M. Mostaza. Unidad de Arteriosclerosis. Hospital Carlos III. Sinesio Delgado, 12. 28029 Madrid. España.
, C. Lahoz
Unidad de Arteriosclerosis. Hospital Carlos III. Madrid. España
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La enfermedad de Alzheimer es un proceso neurodegenerativo crónico caracterizado por un deterioro cognitivo progresivo y por una pérdida creciente de la memoria. Si bien su etiología es desconocida, diversos estudios han demostrado que la fisiopatología de la enfermedad muestra numerosas conexiones con el metabolismo lipoproteico. En este mismo sentido, estudios experimentales y el análisis retrospectivo de grandes cohortes indican que las estatinas podrían interferir en la evolución natural de la enfermedad y reducir su incidencia. Los resultados procedentes de ensayos clínicos no parecen, sin embargo, apoyar estos hallazgos e indican que la acción beneficiosa de estos fármacos podría estar limitada al retraso de su progresión en sujetos con enfermedad ya establecida. Son necesarios nuevos estudios específicamente diseñados para evaluar esta nueva acción.

Palabras clave:
Enfermedad de Alzheimer
Estatinas
Inhibidores de la hidroximetil glutaril CoA reductasa
Deterioro cognitivo
Aß amiloide

Alzheimer's disease is a chronic neurodegenerative process characterized by progressive cognitive deterioration and memory loss. Although its etiology is unknown, several studies have demonstrated that the physiopathology of the disease shows numerous connections with lipoprotein metabolism. Experimental studies and retrospective analyses of large cohorts indicate that statins could influence the natural history of the disease and reduce its incidence. However, the results of clinical trials do not seem to support these findings and indicate that the beneficial effects of these drugs could be limited to delaying progression in subjects with already established disease. Further studies specifically designed to evaluate this new effect are required.

Key words:
Alzheimer's disease
Statins
HMG-CoA reductase inhibitors
Cognitive deterioration
ß-Amyloid
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Bibliografía
[1.]
J.L. Cummings.
Alzheimer's disease.
N Engl J Med, 351 (2004), pp. 56-67
[2.]
S. López-Pousa, J. Vilalta, J. Llinas.
Epidemiología de las demencias en España.
Rev Gerontol, 5 (1995), pp. 28-33
[3.]
M. Simons, P. Keller, S.B. De, K. Beyreuther, C.G. Dotti, K. Simons.
Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons.
Proc Natl Acad Sci USA, 95 (1998), pp. 6460-6464
[4.]
I.L. Notkola, R. Sulkava, J. Pekkanen, T. Erkinjuntti, C. Ehnholm, P. Kivinen, et al.
Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease.
Neuroepidemiology, 17 (1998), pp. 14-20
[5.]
G.P. Jarvik, E.M. Wijsman, W.A. Kukull, G.D. Schellenberg, C. Yu, E.B. Larson.
Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a casecontrol study.
Neurology, 45 (1995), pp. 1092-1096
[6.]
C. Reitz, M.X. Tang, J. Luchsinger, R. Mayeux.
Relation of plasma lipids to Alzheimer disease and vascular dementia.
Arch Neurol, 61 (2004), pp. 705-714
[7.]
H. Kolsch, D. Lutjohann, B.K. Von, R. Heun.
The role of 24S-hydroxycholesterol in Alzheimer's disease.
J Nutr Health Aging, 7 (2003), pp. 37-41
[8.]
R. Mayeux, A.M. Saunders, S. Shea, S. Mirra, D. Evans, A.D. Roses, et al.
Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.
N Engl J Med, 338 (1998), pp. 506-511
[9.]
J.C. Breitner, B.W. Wyse, J.C. Anthony, K.A. Welsh-Bohmer, D.C. Steffens, M.C. Norton, et al.
APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study.
Neurology, 53 (1999), pp. 321-331
[10.]
R.H. Myers, E.J. Schaefer, P.W. Wilson, R. D’Agostino, J.M. Ordovas, A. Espino, et al.
Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study.
Neurology, 46 (1996), pp. 673-677
[11.]
D.B. Carter, E. Dunn, D.D. McKinley, N.C. Stratman, T.P. Boyle, S.L. Kuiper, et al.
Human apolipoprotein E4 accelerates beta-amyloid deposition in APPsw transgenic mouse brain.
Ann Neurol, 50 (2001), pp. 468-475
[12.]
H. Kolsch, U. Ptok, I. Mohamed, S. Schmitz, M.L. Rao, W. Maier, et al.
Association of the C766T polymorphism of the low-density lipoprotein receptor-related protein gene with Alzheimer's disease.
Am J Med Genet, 121B (2003), pp. 128-130
[13.]
S. Locatelli, D. Lutjohann, H.H. Schmidt, C. Otto, U. Beisiegel, B.K. Von.
Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain.
Arch Neurol, 59 (2002), pp. 213-216
[14.]
G.L. Vega, M.F. Weiner, A.M. Lipton, B.K. Von, D. Lutjohann, C. Moore, et al.
Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease.
Arch Neurol, 60 (2003), pp. 510-515
[15.]
K. Fassbender, M. Simons, C. Bergmann, M. Stroick, D. Lutjohann, P. Keller, et al.
Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Aß-42 and Aß-40 in vitro and in vivo.
Proc Natl Acad Sci USA, 98 (2001), pp. 5856-5861
[16.]
M. Sjogren, K. Gustafsson, S. Syversen, A. Olsson, A. Edman, P. Davidsson, et al.
Treatment with simvastatin in patients with Alzheimer's disease lowers both alpha- and beta-cleaved amyloid precursor protein.
Dement Geriatr Cogn Disord, 16 (2003), pp. 25-30
[17.]
M. Simons, F. Schwarzler, D. Lutjohann, B.K. Von, K. Beyreuther, J. Dichgans, et al.
Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: a 26-week randomized, placebo-controlled, double-blind trial.
Ann Neurol, 52 (2002), pp. 346-350
[18.]
K. Hoglund, O. Wiklund, H. Vanderstichele, O. Eikenberg, E. Vanmechelen, K. Blennow.
Plasma levels of beta-amyloid (1-40), betaamyloid (1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins.
Arch Neurol, 61 (2004), pp. 333-337
[19.]
K. Ishii, T. Tokuda, T. Matsushima, F. Miya, S. Shoji, S. Ikeda, et al.
Pravastatin at 10 mg/day does not decrease plasma levels of either amyloid-beta (Aß) 40 or Aß-42 in humans.
Neurosci Lett, 350 (2003), pp. 161-164
[20.]
B. Wolozin, W. Kellman, P. Ruosseau, G.G. Celesia, G. Siegel.
Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors.
Arch Neurol, 57 (2000), pp. 1439-1443
[21.]
H. Jick, G.L. Zornberg, S.S. Jick, S. Seshadri, D.A. Drachman.
Statins and the risk of dementia.
Lancet, 356 (2000), pp. 1627-1631
[22.]
E. Zamrini, G. McGwin, J.M. Roseman.
Association between statin use and Alzheimer's disease.
Neuroepidemiology, 23 (2004), pp. 94-98
[23.]
K. Rockwood, S. Kirkland, D.B. Hogan, C. MacKnight, H. Merry, R. Verreault, et al.
Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people.
Arch Neurol, 59 (2002), pp. 223-227
[24.]
I. Hajjar, J. Schumpert, V. Hirth, D. Wieland, G.P. Eleazer.
The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment.
J Gerontol A Biol Sci Med Sci, 57 (2002), pp. M414-M418
[25.]
G. Li, R. Higdon, W.A. Kukull, E. Peskind, M.K. Van Valen, D. Tsuang, et al.
Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study.
Neurology, 63 (2004), pp. 1624-1628
[26.]
Heart Protection Study Collaborative Group.
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised, placebo-controlled trial.
[27.]
J. Shepherd, G.J. Blauw, M.B. Murphy, E.L. Bollen, B.M. Buckley, S.M. Cobbe, et al.
Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.
Lancet, 360 (2002), pp. 1623-1630
[28.]
Octavo simposium internacional Montreal/Springfield sobre avances en el tratamiento de la enfermedad de Alzheimer. 4 A.D. abril; 2004.

Este trabajo ha sido financiado con la ayuda de la Fundación para el Fomento y Desarrollo de la Investigación Clínica

Copyright © 2005. Sociedad Española de Arteriosclerosis y Elsevier España S.L.
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