This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Aging/ Geriatrics  • Alzheimer Disease  • Cognitive Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Effects of Family History and Apolipoprotein E 4 Status on Cognitive Decline in the Absence of Alzheimer Dementia

The Cache County Study

Kathleen M. Hayden, PhD; Peter P. Zandi, PhD; Nancy A. West, PhD; JoAnn T. Tschanz, PhD; Maria C. Norton, PhD; Chris Corcoran, ScD; John C. S. Breitner, MD, MPH; Kathleen A. Welsh-Bohmer, PhD; for the Cache County Study Group

Arch Neurol. 2009;66(11):1378-1383.

Objective  To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E 4 genotype (APOE 4) 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 4, and cognitive trajectories.

Main Outcome Measure  Modified Mini-Mental State Examination score trajectories over time.

Results  Compared with participants who did not have APOE 4 or an FHxAD, those with APOE 4 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 4 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 4 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 4, 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.

Author Affiliations: 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 (Drs Hayden and Welsh-Bohmer); Department of Mental Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Dr Zandi); Department of Epidemiology, University of Colorado, Denver (Dr West); Departments of Family Consumer and Human Development (Dr Norton), Psychology (Drs Norton and Tschanz), and Mathematics and Statistics (Dr Corcoran), Utah State University, Logan; and Veterans Affairs Puget Sound Health Care System and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle (Dr Breitner).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

This Month in Archives of Neurology
Arch Neurol. 2009;66(11):1320-1321.
FULL TEXT