Active lifestyle associated with less Alzheimer disease-related brain change among persons with APOE ε4 genotype

A sedentary lifestyle is associated with greater cerebral amyloid deposition, which is characteristic of Alzheimer’s disease (AD), among cognitively normal individuals with the ε4 allele of the apolipoprotein E (APOE) gene, according to a report published Online First by Archives of Neurology, one of the JAMA/Archives journals.

“The presence of an APOE ε4 allele is the most established genetic risk factor for Alzheimer disease (AD), with a higher percentage of individuals with AD having an ε4 allele in comparison with the general population,” the authors write as background information in the article. “It has been suggested that APOE status may modify associations between lifestyle factors such as exercise engagement and risk of cognitive decline and dementia.”

To examine the association between exercise and cerebral amyloid deposition among patients with and without the APOE ε4 allele, Denise Head, Ph.D., and colleagues from Washington University in St. Louis, performed APOE genotyping and administered a questionnaire on physical exercise engagement over the last decade to 201 cognitively normal adults (135 women) age 45 to 88 years recruited from the Knight Alzheimer’s Disease Research Center. Samples of cerebrospinal fluid were collected from 165 participants and brain amyloid imaging with positron emission tomography (PET) of the amyloid binding agent carbon 11-labeled Pittsburgh Compound B (PiB) was performed on 163 patients.

Patients who reported higher amounts of exercise had a lower mean (average) cortical PIB binding (binding potential values from the prefrontal cortex, gyrus rectus, lateral temporal, and precuneus regions) than did patients who reported lower amounts of exercise. Participants who were ε4-positive also had higher levels of cortical amyloid compared with individuals negative for the ε4 allele. The authors also observed a “novel interaction between APOE status and exercise engagement for [11C] PiB binding [carbon 11-labeled Pittsburgh Compound B] such that a more sedentary lifestyle was significantly associated with higher [11C] PiB binding for ε4 carriers but not for noncarriers. All findings remain significant after controlling for age; sex; educational level; body mass index; the presence or history of hypertension; diabetes mellitus; heart problems, or depression; and the interval between assessments.”

According to past research “APOE status is associated with increased risk of cognitive decline and elevated amyloid deposition. In contrast, exercise engagement has been associated with reduced risk of cognitive decline and lower levels of amyloid deposition,” the authors note. “In summary, our findings suggest that exercise at levels recommended by the AHA [American Heart Association] may be particularly beneficial in reducing the risk of brain amyloid deposition in cognitively normal ε4-positive individuals.”

Editor’s Note: To contact Denise Head, Ph.D., call Gerry Everding at 314-935-6375 or e-mail For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail