Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease.
BACKGROUND
Statins reduce amyloid-beta (Abeta) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD.


METHODS
In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD.


RESULTS
Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Abeta42 (p=0.344) and total tau levels (p=0.226), yet greater improvements in some measures of verbal fluency (p=0.024) and working memory (p=0.015). APOE4 genotype, gender, and vascular risk factors were associated with CSF biomarker levels, but did not modify treatment effects.


CONCLUSIONS
In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Abeta metabolism, but also other preclinical processes related to the development of AD.
Carlsson
Cynthia M
CM
Department of Medicine, Section of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. cmc@medicine.wisc.edu
Gleason
Carey E
CE
Hess
Timothy M
TM
Moreland
Kimberly A
KA
Blazel
Hanna M
HM
Koscik
Rebecca L
RL
Schreiber
Nathan T N
NT
Johnson
Sterling C
SC
Atwood
Craig S
CS
Puglielli
Luigi
L
Hermann
Bruce P
BP
McBride
Patrick E
PE
Stein
James H
JH
Sager
Mark A
MA
Asthana
Sanjay
S
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000187:drug effects*; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D053327:Apolipoprotein E4 / Q000235:genetics; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D053327:Apolipoprotein E4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D019821:Simvastatin