Engaging in regular physical activity and taking active measures to reduce vascular risk may have a synergistic effect in delaying the progression of Alzheimer disease (AD) by reducing the negative association between β-amyloid (Aβ) burden and cognitive decline in asymptomatic older adults. This according to findings in JAMA Neurology.

Clinically normal participants of the Harvard Aging Brain Study were included in this longitudinal observational study (n=182; mean [SD] age was 73.4 [6.2] years). Only individuals with a baseline Aβ positron emission tomography (PET), medical data quantifying vascular risk, and long-term neuropsychological and structural magnetic resonance imaging (MRI) data were enrolled.

Related Articles

Researchers used a pedometer to measure the mean steps per day in the study group to assess baseline physical activity status. Additionally, carbon 11-labeled Pittsburgh Compound B PET was used to quantify baseline Aβ burden. The Preclinical Alzheimer Cognitive Composite (PACC; median follow-up, 6.0 [interquartile range (IQR), 4.3-6.3] years) was also used to assess cognition, whereas longitudinal structural MRI (2 to 5 scans per participant; median follow-up, 4.5 [IQR, 3.0-5.0] years) was employed to evaluate neurodegeneration.

Continue Reading

The researchers analyzed physical activity and Aβ burden as interactive predictors of decline in PACC as well as volume loss. Analyses were adjusted for age, sex, education, apolipoprotein E ε4 status, and intracranial volume. A second analysis was adjusted for vascular risk and its association with Aβ burden.

An age- and sex-adjusted analysis found a significant association between greater physical activity and a lower vascular risk (partial r = −0.27; P <.001). Researchers also found a significant association between greater physical activity and delayed Aβ-related cognitive decline (β, 0.03; 95% CI, 0.02-0.05; P <.001) as well as slower volume loss (β, 482.07; 95% CI, 189.40-774.74; P =.002).

Additionally, an independent association between slower Aβ-related PACC decline (β, −0.04; 95% CI, −0.06 to −0.02; P <.001) and volume loss (β, −483.41; 95% CI, −855.63 to −111.20; P =.01) was found.

In a secondary model, however, physical activity did not moderate the association between Aβ burden and hippocampal atrophy (β, 3.40; 95% CI, −0.27-7.07; P =.07), nor did it reveal an association between physical activity (ie, physical activity multiplied by time) and hippocampal atrophy (β, −0.89; 95% CI, −5.12-3.34; P =.68).

Limitations of the study included the large number of individuals with an advanced education(thus higher cognitive reserve) and the limited assessment of physical activity (baseline to day 7).

According to the investigators, these findings “support interventions that target both physical activity and management of vascular risk factors as a means of delaying cognitive decline and neurodegeneration in preclinical AD.”

Disclosure: Several of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Rabin JS, Klein H, Kirn DR, et al. Associations of physical activity and β-amyloid with longitudinal cognition and neurodegeneration in clinically normal older adults [published online July 16, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.1879