UCLA

The number of persons aged 65 years and older is expected to double to 92 million in the US by 2060, representing a potentially large social and financial burden of age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and dementias and Parkinson’s disease (PD).Thus effective preventative public health strategies are essential. Regular physical activity (PA) and an active lifestyle have many health benefits, and evidence has accumulated that PA preserves brain structures and functions via multiple physiologic mechanisms, including mediation of inflammation and a general reduction of cardiovascular risk factors.

In the Parkinson’s Environment and Gene (PEG) case-control population-based study, we enrolled 357 incident PD cases and 341 controls in central California and assessed PA levels via self-report of (1) overall PA over 4 age periods; (2) competitive sports; and (3) occupational histories. Our findings suggest that higher lifetime moderate to vigorous activity, especially consistently high level of such activities throughout adulthood and sports activities in youth were negatively associated with PD risk, but we found no beneficial role for occupational physical activity.

We further examine how PA at the late-life influence the risk of dementia/cognitive impairment without dementia (CIND) using a prospective cohort, Sacramento Area Latino Study on Aging (SALSA) study, in which 1789 older Mexican Americans were enrolled at baseline and a majority actively followed between 1998 and 2008. We used Cox proportional hazards regression models to estimate the individual and joint effects of PA, apolipoprotein E (APOE) ε4 and diabetes status on risk of dementia/CIND and observed a nearly 10-fold increased risk among those with all three risk factors. Results from mediation analyses indicate that some of the PA effects on mortality and dementia/CIND but not depression might be mediated through well-known inflammatory pathways represented by biomarkers, specifically interleukins 6 (IL-6) and/or tumor necrosis factor - alpha (TNF-α). However, a large proportion of the PA effects on mortality, cognition, and mood seems to operate independently of the inflammatory pathways or the biomarkers we had available and thus remain unexplained.

Taken together, our results provide support for the hypothesis that PA protects against the onset of neurodegenerative diseases and all-cause mortality, and they suggest that anti-inflammatory action may partly explain the protective effects of PA on dementia/CIND and mortality.