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Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

Kleiman T.a · Zdanys K.a · Black B.a · Rightmer T.a · Grey M.a · Garman K.a · MacAvoy M.a · Gelernter J.b · van Dyck C.a, c
aAlzheimer’s Disease Research Unit; bDivision of Molecular Psychiatry, Department of Psychiatry, and cDepartment of Neurobiology, Yale University School of Medicine, New Haven, Conn., USA Dement Geriatr Cogn Disord 2006;22:73–82 (DOI:10.1159/000093316)


Objective: The apolipoprotein E (ApoE) ε4 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 ε4 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 ε4 dose and any of the retrospective or prospective measures of cognitive or functional decline in this AD patient sample. Conclusions: Although ApoE ε4 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.


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