APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease.
OBJECTIVE
To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD).


METHODS
Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample.


RESULTS
The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses.


CONCLUSIONS
APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.
Cosentino
S
S
Cognitive Neuroscience Division of the Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA.
Scarmeas
N
N
Helzner
E
E
Glymour
M M
MM
Brandt
J
J
Albert
M
M
Blacker
D
D
Stern
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D013997:Time Factors
D053327:Apolipoprotein E4