Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study.
OBJECTIVE
To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E epsilon4 genotype (APOE epsilon4) on cognitive decline.


METHODS
Residents of Cache County, Utah, aged 65 years or older, were invited to participate. At baseline, 2957 participants provided DNA for genotyping of APOE and a detailed FHxAD. They also completed the Modified Mini-Mental State Examination. Cognitive status was reexamined after 3 and 7 years. We used mixed-effects models to examine the association among FHxAD, APOE epsilon4, and cognitive trajectories.


METHODS
Modified Mini-Mental State Examination score trajectories over time.


RESULTS
Compared with participants who did not have APOE epsilon4 or an FHxAD, those with APOE epsilon4 scored lower on the Modified Mini-Mental State Examination at baseline (-0.70 points; 95% confidence interval [CI], -1.15 to -0.24). Participants with an FHxAD and APOE epsilon4 differed less, if at all, in baseline score (-0.46 points; 95% CI, -1.09 to 0.16) but declined faster during the 7-year study (-9.75 points [95% CI, -10.82 to -8.67] vs -2.91 points [95% CI, -3.37 to -2.44]). After exclusion of participants who developed prodromal AD or incident dementia, the group with an FHxAD and APOE epsilon4 declined much less during the 7-year study (-1.54; 95% CI, -2.59 to -0.50).


CONCLUSIONS
Much of the association among FHxAD, APOE epsilon4, and cognitive decline may be attributed to undetected incipient (latent) disease. In the absence of latent disease, the 2 factors do not appear individually to be associated with cognitive decline, although they may be additive.
Hayden
Kathleen M
KM
Department of Psychiatry and Behavioral Sciences and Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27705, USA. khayden@duke.edu
Zandi
Peter P
PP
West
Nancy A
NA
Tschanz
Joann T
JT
Norton
Maria C
MC
Corcoran
Chris
C
Breitner
John C S
JC
Welsh-Bohmer
Kathleen A
KA
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012307:Risk Factors
D053327:Apolipoprotein E4