Jennifer RabinJennifer S. Rabin, PhD
Engaging in physical activity and lowering vascular risk factors may confer a protective effect against cognitive decline and neurodegeneration in older adults with elevated amyloid-beta, according to findings presented at the 2019 Alzheimer’s Association International Conference, July 14-18, in Los Angeles, California.1

Investigators led by Jennifer S. Rabin, PhD, a research scientist at the Sunnybrook Research Institute in Toronto, sought to examine whether physical activity would moderate the association between amyloid-beta and longitudinal cognitive decline and neurodegeneration in people who are clinically normal. They also assessed whether these associations were independent of vascular risk factors.

The study, which was simultaneously published in JAMA Neurology,2 included 182 older adults (56% women, mean age: 73.4) from the Harvard Aging Brain Study. Baseline physical activity was measured with a pedometer; baseline amyloid-beta was measured via PET; cognition was measured annually with the Preclinical Alzheimer Cognitive Composite (PACC); and neurodegeneration, characterized by total gray matter volume loss and regional cortical thickness, was assessed via longitudinal structural MRI.

The investigators recorded a significant interaction between physical activity and amyloid-beta burden when examining PACC decline and volume loss, noting that greater physical activity was linked to slower amyloid-beta-related cognitive decline (β 0.03; 95% CI, 0.02-0.05; P <.001) and volume loss (β 482.07; 95% CI, 189.40-774.74; P =.002). When the investigators adjusted for vascular risk factors, no alterations in association were recorded.

Of note, lower vascular risk, assessed via the Framingham risk score, was independently associated with slower 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).

In a regional analysis, results suggested that in participants with elevated amyloid-beta burden, greater levels of physical activity were associated with slowed cortical thinning in the medial and lateral temporal, medial parietal regions, and insula.

“Our findings are consistent with a rich literature suggesting that greater engagement in physical activity is associated with a lower risk for dementia due to AD,” the investigators wrote.2 “Importantly, these associations remained significant after adjusting for vascular risk, supporting the view that the protective effect of physical activity on cognitive decline and neurodegeneration does not solely occur via mechanisms related to vascular risk.”

They noted that the mechanism by which physical activity exerts a protective effect on longitudinal cognition and cortical thinning remains unclear, suggesting that increased cerebral blood flow, reduced inflammation, increased fibronectin type III domain-containing protein 5/irisin, and upregulation of neuroprotective signaling molecules may play a role. There are also theories that suggest that physical activity has a direct modulation effect on Alzheimer pathology.

“Together, 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,”they concluded.2 “These lifestyle interventions could be coupled with anti-Aβ or anti-tau treatments when they become available.”

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REFERENCES
1. Rabin JS, Klein H, Kirn D, et al. Protective effect of physical activity on longitudinal cognitive decline and neurodegeneration in clinically normal older adults with elevated β-amyloid burden. Presented at: 2019 Alzheimer’s Association International Conference. July 14-18, 2019; Los Angeles, CA. Abstract 29646.
2. 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. JAMA Neurol. Published online July 16, 2019. doi:10.1001/jamaneurol.2019.1879.