Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease.
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 > or =3 prescriptions of > or =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 > or = IV and CERAD rating > or = 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.
Li
G
G
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. gli@u.washington.edu
Larson
E B
EB
Sonnen
J A
JA
Shofer
J B
JB
Petrie
E C
EC
Schantz
A
A
Peskind
E R
ER
Raskind
M A
MA
Breitner
J C S
JC
Montine
T J
TJ
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D001284:Atrophy / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D001921:Brain / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D058225:Plaque, Amyloid / Q000187:drug effects / Q000473:pathology; D012189:Retrospective Studies; D017678:Sex Distribution; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents