Results from a longitudinal study showed physical activity reduced cognitive decline in early APOE4-related Parkinson’s disease.
Jin-Sun Jun, MD, of Hallym University in Seoul, and colleagues in Neurology presented the findings of a longitudinal study on a group of 173 recently diagnosed Parkinson’s patients. Of this group, those who with an apolipoprotein E ε4 (APOE4) allele had faster cognitive decline on the 30-point Montreal Cognitive Assessment (MoCA) scale than noncarriers (estimate -1.33, 95% CI -2.12 to -0.47, P=0.002). However, among the APOE4 carriers, higher physical activity was related to slower cognitive decline (estimate 0.007, 95% CI 0.003-0.011, P=0.001)..
Dr Jun noted that this reflects a number of studies that have demonstrated that Parkinson’s patients who exercise regularly show better clinical outcomes, including motor and cognitive function.
“These observations are supported by epidemiological data showing a link between physical activity and decreased risk for Parkinson’s disease,” Dr Jun told MedPage Today. “Because previous data indicate that physical activity modifies the APOE4 effect on the development and progression of Alzheimer’s disease, we hypothesized that physical activity also plays a role in modulating the association between APOE4 and cognition in Parkinson’s disease.”
Genetic factors interact with physical activity on other health outcomes, noted Jacob Raber, PhD, of Oregon Health and Science University in Portland, and colleagues, in an accompanying editorial.
“If similar gene-by-physical activity interactions were identified in Parkinson’s disease, they could pave the way for personalized treatment,” Raber and colleagues wrote. “While the effects of APOE4 on promoting beta-amyloid and tau pathology are well-established, recent studies show that APOE4 is also associated with more profound pathology of alpha-synuclein and higher measures of cognitive burden, both in mouse models and in humans with Parkinson’s disease.”
In their study, the researchers followed recently diagnosed patients in the Parkinson’s Progression Markers Initiative cohort who were not treated for Parkinson’s and who had abnormal dopamine transporter (DAT) imaging.
Self-reported physical activity was begun 2 years after enrollment and scored on the Physical Activity Scale of the Elderly. Cognitive function was measured annually with the MoCA, which is well-suited for Parkinson’s patients, and DAT imaging was performed at years 2 and 4. Assessments performed at years 2, 3, and 4 were used for analysis.
There was no significant interaction seen between physical activity and APOE4 involving change in striatal DAT activities. This suggests that striatal dopaminergic function may not be a major factor in physical activity’s protective effect on APOE4-related cognitive decline, Dr Jun and colleagues noted. “These negative results may be explained by the modest effect of APOE4 on the nigrostriatal dopaminergic system,” they wrote. “Furthermore, our follow-up duration may be too short to comprehend the impact of APOE4 on this system, considering the slow progressive nature of alpha-synucleinopathy.”
The researchers also pointed out that the exercise could offer benefits through mechanisms unrelated to the disease. “Although we cannot conclude what types or amounts of exercise help to slow progression from this study design, even non-high-intensity physical activity positively modified the impact of APOE4 on cognitive function,” Jun said.
The study’s limitations included physical activity being self-reported, cognitive function being based only on MoCA scores, and a short follow-up time. Though motor scores in the off-medication state were adjusted for, physical activity may have been less due to disease progression.
Source: MedPage Today
