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NEUROLOGY 2007;69:878-885
© 2007 American Academy of Neurology

Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease

G. Li, MD, PhD, E. B. Larson, MD, MPH, J. A. Sonnen, MD, J. B. Shofer, MS, E. C. Petrie, MD, A. Schantz, MA, E. R. Peskind, MD, M. A. Raskind, MD, J.C.S. Breitner, MD, MPH and T. J. Montine, MD, PhD

From the Departments of Psychiatry and Behavioral Sciences (G.L., J.B.S., E.C.P., E.R.P., M.A.R., J.C.S.B.), Pathology (J.A.S., A.S., T.J.M.), and Medicine (E.B.L.), University of Washington, Mental Illness Research and Education Clinical Center (MIRECC) (E.C.P., E.R.P., M.A.R.) and Geriatric Research, Education, and Clinical Center (GRECC) (J.C.S.B.), Veterans Affairs Puget Sound Health Care System, and Center for Health Studies (E.B.L.), Group Health Cooperative, Seattle, WA.

Address correspondence and reprint requests to Dr. G. Li, VA Puget Sound Health Care System, 1660 South Columbian Way, Mail Code S-116 6 East, Seattle, WA 98108-1597 gli{at}u.washington.edu

Background: Treatment with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors ("statins") has been associated in some epidemiologic studies with reduced risk of Alzheimer disease (AD). However, direct evidence of statin effects on neuropathologic markers of AD is lacking. We investigated whether antecedent statin exposure is associated with neuritic plaque (NP) or neurofibrillary tangle (NFT) burden in a population-based sample of human subjects.

Methods: Brain autopsies were performed on 110 subjects, ages 65 to 79 years, who were cognitively normal at enrollment into the Adult Changes in Thought Study. Neuropathologic findings were compared between statin users with ≥3 prescriptions of ≥15 pills of simvastatin, pravastatin, lovastatin, or atorvastatin vs nonusers, based on pharmacy dispensing records.

Results: After controlling for age at death, gender, cognitive function at study entry, brain weight, and presence of cerebral microvascular lesions, the odds ratio (OR) for each unit increase in Braak NFT stage in statin users vs nonusers was 0.44 (95% CI: 0.20 to 0.95). The OR for each unit increase in Consortium to Establish a Registry for Alzheimer's Disease (CERAD) staging of NPs did not deviate significantly from unity (OR 0.69; 95% CI: 0.32 to 1.52). However, the risk for typical AD pathology (Braak stage ≥ IV and CERAD rating ≥ moderate) was reduced in statin users (OR 0.20; 95% CI: 0.05 to 0.86).

Conclusions: These findings demonstrate an association between antecedent statin use and neurofibrillary tangle burden at autopsy. Additional study is needed to examine whether statin use may be causally related to decreased development of Alzheimer disease–related neuropathologic changes.

Supported in part by grants K23AG020020, U01AG006781, R01AG023801, P50AG005136, and K08AG023670 from the National Institute on Aging.

Disclosure: The authors report no conflicts of interest.

Received February 13, 2007. Accepted in final form April 20, 2007.




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Correspondence:

Read all Correspondence

Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease
George J. Siegel, et al.
Neurology Online, 4 Dec 2007 [Full text]
Reply from the authors
Ge Li, et al.
Neurology Online, 4 Dec 2007 [Full text]
Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease
Beatrice A. Golomb, MD, PhD, et al.
Neurology Online, 4 Feb 2008 [Full text]
Reply from the authors.
Ge Li, et al.
Neurology Online, 4 Feb 2008 [Full text]

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