Physical activity slows cognitive decline in APOE e4 carriers with Parkinson’s disease

Patients with Parkinson’s disease who increased their physical activity saw positive modification of the APOE e4 allele’s impact on early cognitive decline, according to findings from a multicenter cohort study published in Neurology.

The allele is recognized as “a major genetic risk factor” for Alzheimer’s disease and new data has shown it plays a role in cognitive impairment among patients with Parkinson’s disease, according to the researchers.

“Previous data indicate that physical activity modifies the APOE e4 effect on the development and progression of AD,” Ryul Kim, MD, of the department of neurology at Inha University Hospital in South Korea, and colleagues wrote. “These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE e4 and cognition in PD. However, no studies have yet reported on this interaction in [patients with PD].”

Kim and colleagues analyzed data from the Parkinson’s Progression Markers Initiative (PPMI) cohort, an international, multicenter cohort study developed to determine progression biomarkers in PD. They looked at 173 patients with PD (age, 63.3±10 years; 27% APOE e4 carriers) and implemented a baseline of at least 2 years follow up. The researchers evaluated physical activity using the Physical Activity Scale of the Elderly (PASE), a self-reported questionnaire that tracks the frequency, intensity and duration of activities in the previous week, and cognitive function using the Montreal Cognitive Assessment (MoCA).

Carriers of the APOE e4 allele tended to be younger (mean age, 60.9 years) than noncarriers (mean age, 64.1 years).

The researchers observed no significant association physical activity and longitudinal cognitive performance, but the interaction between physical activity, APOE e4 and time was significant; Kim and colleagues found higher physical activity linked to slower APOE e4-related cognitive decline (estimate, 0.007; 95% CI 0.003 to 0.011; t = 3.22; P = .001). In post hoc subgroup analyses, both high intensity (estimate, 0.018; 95% CI, 0.006-0.029; t = 2.91; P = .004) and non-high intensity (estimate, 0.007; 05% CI, 0.002-0.012; t = 2.65; P = .008) physical activity correlated with decreased APOE e4-related cognitive decline.

According to the researchers, the subjective, self-reported measure of physical activity they used correlated with the risk for introducing recall bias. However, they also noted that the PASE “is strongly correlated with objective measures of physical activity.”

“Our results showed a significant association between greater physical activity and less APOE e4-related cognitive decline in the early stages of PD, which may support interventions that target physical activity as a means of delaying cognitive decline in early PD patients with the APOE e4 allele,” Kim and colleagues wrote.

In a related editorial, Jacob Raber PhD, of the departments of behavioral neuroscience, neurology and radiation medicine in the division of neuroscience at Oregon Health & Science University, Sirwan K.L. Darweesh, MD, PhD, of the department of neurology at Radboud University Medical Center of Expertise for Parkinson & Movement Disorder in the Netherlands, and Rodolfo Savica, MD, PhD, FAAN, of the department of neurology and health science research at Mayo Clinic Rochester in Minnesota, discussed the treatment implications of the study results from Kim and colleagues, since “physical activity has emerged as a promising avenue for treatment.”

According to the authors, if the “important” results from Kim and colleagues are replicated, they could guide targeted lifestyle interventions for patients with PD.

“... If effective therapeutic strategies to slow cognitive decline become available for e4-carrying patients with other neurodegenerative disorders, these strategies should also be examined in e4-carrying patients with PD,” Raber, Darweesh and Savica wrote.

“Problems with thinking skills and memory can have a negative impact on people’s quality of life and ability to function, so it’s exciting that increasing physical activity could have the potential to delay or prevent cognitive decline,” study author Jin-Sun Jun, MD, of the department of neurology at Hallym University in South Korea, said in a press release.