Apolipoprotein E epsilon4 allele is unrelated to cognitive or functional decline in Alzheimer's disease: retrospective and prospective analysis.
OBJECTIVE
The apolipoprotein E (ApoE) epsilon4 allele is a well-documented genetic risk factor for Alzheimer's disease (AD). Its role, if any, in the progression of cognitive and functional impairment in AD has been the subject of discrepant reports in the literature. This study aimed to determine whether ApoE epsilon4 dose is related to the progression of cognitive and functional decline in AD patients by combined retrospective and prospective analyses.


METHODS
A sample of 366 AD patients was genotyped for ApoE. Subjects received tests of cognition (Mini-Mental State Examination, MMSE; Alzheimer's Disease Assessment Scale-Cognitive subscale, ADAS-Cog) and daily function (Instrumental Activities of Daily Living, IADL; Alzheimer's Disease Cooperative Study-Activities of Daily Living, ADCS-ADL) at baseline and at multiple subsequent time points during their participation in a variety of research protocols. In retrospective analyses, scores on baseline cognitive and functional measures were compared cross-sectionally among genotype groups, controlling for duration of symptoms. In prospective analyses, longitudinal rates of change for each measure were computed by linear regression and compared across genotype groups.


RESULTS
No association was observed between ApoE epsilon4 dose and any of the retrospective or prospective measures of cognitive or functional decline in this AD patient sample.


CONCLUSIONS
Although ApoE epsilon4 increases the risk for AD and decreases the age of disease onset in population studies, it did not significantly influence the rate of disease progression in cognitive or functional domains in our sample.
Kleiman
Timothy
T
Alzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.
Zdanys
Kristina
K
Black
Benjamin
B
Rightmer
Tracy
T
Grey
Monique
M
Garman
Katherine
K
Macavoy
Martha
M
Gelernter
Joel
J
van Dyck
Christopher
C
D000203:Activities of Daily Living; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics* / Q000523:psychology; D018450:Disease Progression; D004493:Education; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012189:Retrospective Studies
D053327:Apolipoprotein E4; D001057:Apolipoproteins E