Statins and cognitive function in the elderly

Objective: To examine the association of statin drug use on cognitive and MRI change in older adults. Methods: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy. Results: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of >80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups. Conclusion: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

[1]  M. Etminan,et al.  Season of birth and risk of brain tumors in adults , 2004, Neurology.

[2]  E. B. Larson,et al.  Statin therapy and risk of dementia in the elderly , 2004, Neurology.

[3]  J. Shepherd,et al.  Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial , 2003 .

[4]  P. Macfarlane,et al.  Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial , 2002, The Lancet.

[5]  K. Fassbender,et al.  Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide , 2002, Neurology.

[6]  J. Dichgans,et al.  Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26‐week randomized, placebo‐controlled, double‐blind trial , 2002, Annals of neurology.

[7]  AndrewJ. S. Coats MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[8]  J. Buxbaum,et al.  Pharmacological concentrations of the HMG-CoA reductase inhibitor lovastatin decrease the formation of the Alzheimer beta-amyloid peptide in vitro and in patients. , 2002, Frontiers in bioscience : a journal and virtual library.

[9]  E. Barrett-Connor,et al.  Serum lipoprotein levels, statin use, and cognitive function in older women. , 2002, Archives of neurology.

[10]  S. Yusuf MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Commentary , 2002 .

[11]  T. Golde,et al.  Cholesterol modulation as an emerging strategy for the treatment of Alzheimer's disease. , 2001, Drug discovery today.

[12]  J. Dichgans,et al.  Cholesterol and Alzheimer’s disease: Is there a link? , 2001 .

[13]  D. Williams,et al.  Membrane cholesterol modulates serotonin transporter activity. , 2001, Biochemistry.

[14]  A. Koudinov,et al.  Essential role for cholesterol in synaptic plasticity and neuronal degeneration , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  H. Soininen,et al.  Midlife vascular risk factors and late-life mild cognitive impairment , 2001, Neurology.

[16]  J Tuomilehto,et al.  Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study , 2001, BMJ.

[17]  E. Kojro,et al.  Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Bergmann,et al.  Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[19]  C. Schweiger [Statins and the risk of dementia]. , 2001, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[20]  E. Kojro,et al.  Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  R. Haley,et al.  Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease? , 2000, Archives of neurology.

[22]  G. Celesia,et al.  Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. , 2000, Archives of neurology.

[23]  Rong Wang,et al.  Hypercholesterolemia Accelerates the Alzheimer's Amyloid Pathology in a Transgenic Mouse Model , 2000, Neurobiology of Disease.

[24]  K. Hall,et al.  Serum cholesterol, APOE genotype, and the risk of Alzheimer’s disease: A population-based study of African Americans , 2000, Neurology.

[25]  R. Laaksonen,et al.  Low-density lipoprotein-independent effects of statins. , 1999, Current opinion in lipidology.

[26]  R. Caldwell,et al.  Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. , 1999, Journal of the American College of Cardiology.

[27]  T. Manolio,et al.  Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. , 1998, Archives of neurology.

[28]  R. Rosenson,et al.  Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. , 1998, JAMA.

[29]  B. Strooper,et al.  Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Nissinen,et al.  Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. , 1998, Neuroepidemiology.

[31]  C. Jack MR imaging of the brain in epidemiologic research: the Cardiovascular Health Study. , 1997, Radiology.

[32]  L. Fried,et al.  Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. , 1996, Stroke.

[33]  L H Kuller,et al.  Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study. , 1995, Annals of epidemiology.

[34]  E M Wijsman,et al.  Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease , 1995, Neurology.

[35]  L. Mucke,et al.  Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein , 1995, Nature.

[36]  Teri,et al.  A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study. , 1994, AJNR. American journal of neuroradiology.

[37]  E P Steinberg,et al.  Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study. , 1994, Stroke.

[38]  J. Gardin,et al.  Assessment of cerebrovascular disease in the Cardiovascular Health Study. , 1993, Annals of epidemiology.

[39]  L. Fried,et al.  Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. , 1993, Annals of epidemiology.

[40]  R. Kronmal,et al.  The Cardiovascular Health Study: design and rationale. , 1991, Annals of epidemiology.

[41]  H. Chui,et al.  The Modified Mini-Mental State (3MS) examination. , 1987, The Journal of clinical psychiatry.