Study identifies factors for minimizing the impact of Alzheimer’s genetic risk


Participants in the Health, Aging, and Body Composition study who carried the apolipoprotein E–epsilon 4 allele had some degree of protection from the cognitive decline for which they are at high risk if they had behaviors that enhanced cognitive reserve or improved certain other psychosocial and health factors.

Allison R. Kaup, Ph.D., of Sierra Pacific Mental Illness Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center, and her associates analyzed data collected in the prospective Health ABC (Health, Aging, and Body Composition) study to identify factors that may promote cognitive resilience in carriers of the apolipoprotein E–epsilon 4 (APOE e4) allele. The study examined aging-related health in 3,075 older adults residing in Pittsburgh or Memphis in 1997-98. These study participants, aged 69-80 years at baseline, had repeated cognitive testing during 11 years of follow-up. A subset of 670 were APOE e4 carriers.

As expected, APOE e4 carriers showed greater cognitive decline over time than noncarriers; however, a subset of APOE e4 carriers showed high retention of cognitive status in comparison with demographically similar noncarriers. Among white carriers, the factors that strongly predicted cognitive resilience were, in order of importance, an absence of recent negative life events, higher literacy level, older age, higher education level, and more time spent reading. Among black carriers, the factors that most strongly predicted cognitive resilience were higher literacy level, higher education level, female sex, and absence of diabetes mellitus.

The reasons why some predictors differed by race aren’t yet understood. The investigators analyzed the two races separately because there are racial differences in the frequency of APOE e4 carriage (it occurs more frequently in blacks than in whites) and in its impact (its deleterious effects on cognition are weaker in blacks than in whites).

Their findings “raise the possibility that interventions targeting the modifiable factors among these predictors could help promote cognitive resilience in APOE e4 carriers,” Dr. Kaup and her associates said ( JAMA Neurol. 2015;72:340-8 ). For example, promoting cognitive reserve would likely be protective across both races. In addition, whites would likely benefit most from stress reduction or stress management, while blacks would likely benefit most from prevention or close management of diabetes.

This study was supported by the National Institute on Aging, the National Institute on Nursing Research, the U.S. Department of Veterans Affairs, the San Francisco VA Medical Center, and the Sierra Pacific Mental Illness Research, Education, and Clinical Center. Dr. Kaup reported having no financial disclosures; her associates reported ties to Navidea Biopharmaceuticals, Novartis, Pfizer, Takeda, and Beeson.


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