Physical Activity Could Slow Alzheimer’s Disease

Physical activity could protect against several key hallmarks of Alzheimer’s disease (AD), research suggests.

The study showed that exercise may help delay cognitive decline by having a positive impact on neurodegeneration and abnormal tau proteins in the brain. Benefits were seen for the AD biomarkers phosphorylated-tau (ptau)217 and neurofilament light chain (NfL).

The findings, reported in JAMA Network Open, suggested that physical activity was particularly important for older individuals.

“In this cross-sectional study, [physical activity] was associated with lower plasma ptau217 and NfL levels and better cognition, suggesting a potential role in delaying cognitive decline by modulating neurodegeneration and AD pathophysiology,” the researchers summarized.

Physical activity is widely recommended for Alzheimer’s, with potential cognitive benefits on neuroplasticity, neuroinflammation, and cerebral blood flow, but few studies have examined its impact on the full spectrum of disease biomarkers.

To investigate further, Seung Ae Kim, from Seoul National University in South Korea, and colleagues examined the association of physical activity, plasma biomarkers, and cognition among people with and without cognitive impairment who were recruited at memory clinics.

Plasma biomarkers included β-amyloid (Aβ)42/40, ptau217, NfL, and glial fibrillary acidic protein (GFAP).

The 1,144 participants were recruited from the large Precision Medicine Platform for Mild Cognitive Impairment Based on Multi-omics, Imaging, Evidence-Based R&BD (PREMIER) Consortium, which involved 25 centers across South Korea.

This research initiative aims to develop personalized treatments for mild cognitive impairment by consolidating genetic information, brain imaging scans, and clinical assessments to determine unique patient profiles and to individually tailor treatment.

Results showed that individuals in the highest quartile of physical activity had significantly lower ptau217 and NfL than those in the lowest quartile. NfL was the biomarker most consistently associated with physical activity.

Higher quartiles of physical activity were associated with better cognitive scores, assessed using the Mini-Mental State Examination and the Clinical Dementia Rating-Sum of Boxes, after adjusting for potential confounding factors.

A subgroup analysis revealed that the associations between physical activity and plasma biomarkers with cognition were more pronounced in people aged at least 65 years and the cognitively impaired compared with the younger and cognitively unimpaired groups.

In the cognitively impaired group, physical activity significantly tracied with ptau217, GFAP, and NfL levels, which the investigators say indicates its association with more advanced AD processes, including tauopathy, glial activation, and neuronal injury.

Further analysis indicated that physical activity might impact cognition both directly and indirectly through AD pathophysiology.

Plasma NfL and ptau217 partially mediated the associations of physical activity with cognition, which the researchers suggest could indicate that it improves cognition by delaying neurodegeneration and tau pathophysiology, independently of Aβ burden.

“In addition, [physical activity] may directly enhance cognitive and functional performance through mechanisms beyond those captured by plasma biomarkers,” they postulated.

“These mechanisms could include improved cardiovascular health, increased cerebral blood flow, enhanced neuroplasticity, and better management of mood or physical frailty.”