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. 2009 Nov;66(11):1378-83.
doi: 10.1001/archneurol.2009.237.

Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study

Kathleen M Hayden  1 , Peter P Zandi, Nancy A West, Joann T Tschanz, Maria C Norton, Chris Corcoran, John C S Breitner, Kathleen A Welsh-Bohmer; Cache County Study Group
Collaborators, Affiliations

Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study

Kathleen M Hayden et al. Arch Neurol. 2009 Nov.

Abstract

Objective: To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E epsilon4 genotype (APOE epsilon4) on cognitive decline.

Design, setting, and participants: 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.

Main outcome measure: 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.

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Figures

Figure 1
Figure 1
Trajectories of cognitive change by FhxAD and APOE status
Figure 2
Figure 2
Trajectories of cognitive change by FhxAD and APOE status among cognitively normal individuals
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