Cognitive impairment in Alzheimer's disease is modified by APOE genotype.
OBJECTIVE
We examined whether impairment in specific cognitive domains in Alzheimer's disease (AD) differed according to APOE genotype and age at onset.


METHODS
Cognitive functions of 229 consecutive AD patients were assessed using Visual Association Test (VAT), Memory Impairment Screen+ (MIS+), VAT object naming, fluency test and Trail Making Test (TMT). Dementia severity was assessed using MMSE. ANOVAs were performed with APOE genotype and age at onset as independent variables and sex, education and MMSE as covariates.


RESULTS
28% of patients were APOE epsilon4-negative, 58% heterozygous and 14% homozygous. A significant association between APOE genotype and VAT and MIS+ was found when correcting for sex and education. An interaction effect between APOE genotype and age at onset on VAT and VAT object naming was found, with young carriers performing worse than young noncarriers. By contrast, when additionally correcting for MMSE, a significant association between APOE genotype and VAT object naming, TMT-A and TMT-B was found, with noncarriers performing worse than carriers.


CONCLUSIONS
Memory was more impaired among APOE epsilon4 carriers than among noncarriers. By contrast, naming, executive functions and mental speed were more impaired among APOE epsilon4 noncarriers. This suggests that the APOE genotype modifies the clinical phenotype in terms of cognitive impairment in AD.
van der Vlies
Annelies E
AE
Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands. ae.vdvlies@vumc.nl
Pijnenburg
Yolande A L
YA
Koene
Teddy
T
Klein
Martin
M
Kok
Astrid
A
Scheltens
Philip
P
van der Flier
Wiesje M
WM
D000367:Age Factors; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D000849:Anomia / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D011340:Problem Solving; D011594:Psychometrics / Q000706:statistics & numerical data; D011930:Reaction Time; D013223:Statistics as Topic
D053327:Apolipoprotein E4; D001057:Apolipoproteins E