HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, G. Articles by Montine, T. J. Search for Related Content PubMed PubMed Citation Articles by Li, G. Articles by Montine, T. J. Related Collections Other cerebrovascular disease/ Stroke Alzheimer's disease Risk factors in epidemiology

Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease

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.

This article has been cited by other articles:

				H. M. Hussain, M. Zakria, A. R. Arshad, Z. Arvanitakis, D. A. Bennett, M. A. Pappolla, Z. Arvanitakis, and D. A. Bennett STATINS, INCIDENT ALZHEIMER DISEASE, CHANGE IN COGNITIVE FUNCTION, AND NEUROPATHOLOGY Neurology, December 9, 2008; 71(24): 2019 - 2020. [Full Text] [PDF]

				M. S. Beeri, J. Schmeidler, J. M. Silverman, S. Gandy, M. Wysocki, C. M. Hannigan, D. P. Purohit, G. Lesser, H. T. Grossman, and V. Haroutunian Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology Neurology, September 2, 2008; 71(10): 750 - 757. [Abstract] [Full Text] [PDF]

				C. Cramer, M. N. Haan, S. Galea, K. M. Langa, and J. D. Kalbfleisch Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study Neurology, July 29, 2008; 71(5): 344 - 350. [Abstract] [Full Text] [PDF]

				G. J. Siegel, N. B. Chauhan, D. L. Feinstein, G. Li, E. B. Larson, J. C.S. Breitner, and T. J. Montine STATIN THERAPY IS ASSOCIATED WITH REDUCED NEUROPATHOLOGIC CHANGES OF ALZHEIMER DISEASE Neurology, July 29, 2008; 71(5): 383 - 383. [Full Text] [PDF]

				B. A. Golomb, M. A. Evans, G. Li, J. C.S. Breitner, and T. J. Montine STATIN THERAPY IS ASSOCIATED WITH REDUCED NEUROPATHOLOGIC CHANGES OF ALZHEIMER DISEASE Neurology, June 10, 2008; 70(24): 2349 - 2330. [Full Text] [PDF]

				Z. Arvanitakis, J. A. Schneider, R. S. Wilson, J. L. Bienias, J. F. Kelly, D. A. Evans, and D. A. Bennett Statins, incident Alzheimer disease, change in cognitive function, and neuropathology Neurology, May 6, 2008; 70(19_Part_2): 1795 - 1802. [Abstract] [Full Text] [PDF]

				J. R. Holman Some Docs in Denial About Statin Side Effects DOC News, December 1, 2007; 4(12): 1 - 12. [Full Text]

				L. C. Silbert Does statin use decrease the amount of Alzheimer disease pathology in the brain? Neurology, August 28, 2007; 69(9): E8 - E11. [Full Text] [PDF]

Correspondence: