The apolipoprotein E epsilon 2 allele and decline in episodic memory.
OBJECTIVE
The apolipoprotein E (apoE) epsilon 4 allele is related to decline in multiple cognitive domains, especially episodic memory, but the effect of the epsilon 2 allele on change in different forms of cognitive function has been difficult to establish.


METHODS
Participants are from the Religious Orders Study. At baseline, they were at least 65 years old and free of clinical evidence of dementia. For up to eight years, they underwent annual clinical evaluations that included detailed cognitive function assessment from which previously established summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. Growth curve models were used to assess change in each measure and its relation to apoE genotype, controlling for age, sex, education, and baseline level of cognition. Follow up data were available in 669 persons (98% of those eligible). We treated those with the epsilon 3/3 genotype as the reference group (n=425), which was contrasted with epsilon 2 ( epsilon 2/2, epsilon 2/3; n=86), and epsilon 4 ( epsilon 3/4, epsilon 4/4; n=158) subgroups.


RESULTS
Rate of episodic memory change in the three subgroups significantly differed, with an average annual increase of 0.016 units in the epsilon 2 subgroup and annual decreases of 0.022 units in those with epsilon 3/3 and of 0.073 units in the epsilon 4 subgroup. The epsilon 2 subgroup did not differ from those with epsilon 3/3 in rate of decline in other cognitive systems. The epsilon 4 subgroup declined more rapidly than those with epsilon 3/3 in semantic memory and perceptual speed but not in working memory or visuospatial ability.


CONCLUSIONS
Possession of one or more apoE epsilon 2 alleles is associated with reduced decline in episodic memory in older persons.
Wilson
R S
RS
Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Department of Neurological Sciences, Rush-Presbyterian-St Luke's Medical Center, Chicago, USA. rwilson@rush.edu
Bienias
J L
JL
Berry-Kravis
E
E
Evans
D A
DA
Bennett
D A
DA
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000502:physiology; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects; D012016:Reference Values
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E