Document Detail


Influence of apolipoprotein E varepsilon4 on rates of cognitive and functional decline in mild cognitive impairment.
MedLine Citation:
PMID:  20813342     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Apolipoprotein E varepsilon4 (APOE varepsilon4) allele carrier status has been well established as a risk factor for developing Alzheimer's disease. However, the specific influence of APOE varepsilon4 allele status on cognitive and functional rates of decline in mild cognitive impairment (MCI) is poorly understood. We examine the prospective association of APOE varepsilon4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI).
METHODS: A total of 516 aMCI participants aged 55-90 years who received placebo or vitamin E from the Alzheimer's Disease Cooperative Study's MCI treatment trial were evaluated. During the 36-month study period, neurocognitive and functional measures were collected. These measures were assessed over time for change and association with APOE varepsilon4 status. Generalized Estimating Equations were performed to model each outcome measure over the study period.
RESULTS: APOE varepsilon4 status had a significant impact on cognitive and functional decline on multiple measures; those who were APOE varepsilon4 positive had significantly more rapid decline in performance on all cognitive and functional measures except Number Cancellation and Maze tracing (P < .05). The greatest decline was seen in global measures of cognition and function including the Clinical Diagnostic Rating scale, followed by the Mini-Mental State Examination, Global Deterioration scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale.
CONCLUSIONS: These findings demonstrate that APOE varepsilon4 genotype is predictive of increased general rates of decline with global measures of cognition and function most affected. With accelerated declines in common clinical trial primary efficacy measures, APOE varepsilon4 status needs to be accounted for in treatment trials of MCI.
Authors:
Danielle C Whitehair; Abdullah Sherzai; Jennifer Emond; Rema Raman; Paul S Aisen; Ronald C Petersen; Adam S Fleisher;
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Alzheimer's & dementia : the journal of the Alzheimer's Association     Volume:  6     ISSN:  1552-5279     ISO Abbreviation:  Alzheimers Dement     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-03     Completed Date:  2010-12-20     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  101231978     Medline TA:  Alzheimers Dement     Country:  United States    
Other Details:
Languages:  eng     Pagination:  412-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 The Alzheimer
Affiliation:
Department of Neurosciences, University of California, San Diego, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Apolipoprotein E4 / genetics*
Cholinesterase Inhibitors / therapeutic use
Cognition Disorders / drug therapy,  genetics*
Disease Progression
Female
Follow-Up Studies
Genotype
Humans
Indans / therapeutic use
Male
Middle Aged
Neuropsychological Tests
Piperidines / therapeutic use
Psychiatric Status Rating Scales
Randomized Controlled Trials as Topic
Retrospective Studies
Vitamin E / therapeutic use
Grant Support
ID/Acronym/Agency:
U01 AG010483-19S1/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein E4; 0/Cholinesterase Inhibitors; 0/Indans; 0/Piperidines; 120011-70-3/donepezil; 1406-18-4/Vitamin E
Comments/Corrections

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