Apolipoprotein E genotype and memory in the sixth decade of life.
BACKGROUND
Virtually all adult studies of APOE genotypes and cognition have included individuals over 60. In older adults, epsilon 4 carriers may manifest greater cognitive asymmetries than non-epsilon 4 carriers even in the absence of overall mean differences. General cognitive ability may also be affected by aging and APOE genotype, but most studies have inadequately addressed this potential confound. The goals of this study were to examine, in middle age, the relationship of APOE genotype with episodic memory and verbal-visuospatial episodic memory asymmetries, after accounting for prior general cognitive ability.


METHODS
We compared epsilon 4+ and epsilon 4- individuals in 626 male twins in their 50s. We examined verbal and visuospatial episodic memory and verbal-visual asymmetry scores after adjusting for cognitive ability at age 20. Analyses corrected for correlations between twin pair members.


RESULTS
Compared with epsilon 4- individuals, epsilon 4 carriers performed significantly more poorly on verbal, but not visuospatial memory, manifested significantly greater cognitive asymmetry, and also had significantly more concerns about memory. At age 20, epsilon 4 carriers had higher general cognitive ability than epsilon 4- individuals, and current memory differences were enhanced after adjusting for age 20 cognitive ability.


CONCLUSIONS
Small, but significant, APOE-epsilon 4-related memory deficits appear in the sixth decade of life in individuals who show no signs of preclinical dementia. The results partially support studies of older adults that suggest that increased cognitive asymmetries reflect risk for dementia and are associated with the APOE-epsilon 4 genotype. The results also highlight the potential problems of not having accurate data on prior cognitive ability.
Schultz
M R
MR
Department of Psychology, Boston University, Boston, MA, USA.
Lyons
M J
MJ
Franz
C E
CE
Grant
M D
MD
Boake
C
C
Jacobson
K C
KC
Xian
H
H
Schellenberg
G D
GD
Eisen
S A
SA
Kremen
W S
WS
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics; D012307:Risk Factors
D053327:Apolipoprotein E4; D020033:Protein Isoforms