Clinicians are increasingly interested in the efficacy of interventions for preventing complex chronic diseases, including dementia. Physical activity improves mild cognitive impairment and dementia through neurotrophic factors and mitigating cerebrovascular risk. New research is showing it may also modulate Alzheimer’s disease (AD) specific pathology.
The Study
A recent study published in the Lancet evaluated associations between physical activity, cognition, and Alzheimer’s disease blood markers. Researchers used the Multidomain Alzheimer’s Preventive Trial [MAPT] data in a follow-up analysis to assess phosphorylated (p)-tau181 measurements. The MAPT trial was a multicenter study on 1679 community-dwelling adults aged 70 and older who did not have dementia. Only 558 (33%) had p-tau measurements, which made up this study’s cohort. Other inclusion criteria involved self-reported spontaneous memory complaints, low gait speed, or limitation in at least one activity of daily living (ADL). Exclusion criteria eliminated individuals with diagnosed dementia, a Mini Mental Status Exam (MMSE) lower than 24, limitations in ADLs (score lower than 6), or supplementing with omega-3 fatty acids.
Researchers measured phosphorylated (p)-tau181 blood concentrations at baseline, 3 years, or both time points. Tau proteins are abundant in neurons and regulate structural microtubule activity and cell signaling. Phosphorylated tau proteins are dysfunctional and aggregate to form neurofibrillary tangles, a hallmark of AD pathology. Neurons with neurofibrillary tangles impair cell signaling and may undergo apoptosis. Neuronal dysfunction and death lead to brain atrophy and progressive cognitive, behavioral, and motor impairment.
Physical activity and cognition were assessed at baseline, 6 months, and annually for 3 years. The Minnesota Leisure Time Activities questionnaire was used to estimate physical activity level. The questionnaire assesses frequency and duration of household and leisure time physical activity over 2 weeks. A calculation was applied to obtain a total weekly volume of physical activity. Four validated tests were used to assess cognition.
41 (7%) of 558 individuals were classified as inactive, 264 (47%) with low levels of moderate-to-vigorous physical activity, and 253 (45%) with high levels of moderate-to-vigorous physical activity. Increased moderate-to-vigorous activity levels were associated with better cognition and a delayed rise in p-tau181 concentrations over the 3-year follow-up period. Patients with higher baseline p-tau181 levels did not have as dramatic an effect. The study was not conducted on patients with AD who would be expected to have higher p-tau181 levels at baseline. What this suggests is that physical activity is preventative against neurodegeneration, whereas in patients with AD, the effects are likely modest.
Conclusions
This study shows that moderate-to-vigorous physical activity may delay cognitive decline by modulating AD-specific pathology over a 3-year time frame in older adults. Longitudinal studies like this one are important for assessing cause and effect. Many prior studies have a cross-sectional design, which limits causal inference. Another recent study showed that as little as 35 minutes of moderate-to-vigorous physical activity per week is associated with a 41% lower risk of developing dementia. Moderate-to-vigorous physical activity should be encouraged in all patients for cognitive and overall health.
