Exercise May Slow Cognitive Decline in At-Risk Patients With Parkinson Disease

March 31, 2021
Matthew Gavidia
Matthew Gavidia

Matthew is an associate editor of The American Journal of Managed Care® (AJMC®). He has been working on AJMC® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

Exercise may reduce vulnerability to cognitive decline among at-risk patients with Parkinson disease who have the gene variant APOE ε4.

Exercise may reduce vulnerability to cognitive decline among patients with Parkinson disease (PD) at greater risk due to the gene variant apolipoprotein E ε4 (APOE ε4), according to study findings published today in Neurology.

As a major genetic risk factor for Alzheimer disease (AD), the APOE ε4 allele has been shown to affect cognition in patients with AD mainly through amyloid-related pathways. Although, the researchers noted that recent evidence has indicated that the allele may also exacerbate alpha synuclein pathology in the brain, which would then lead to accelerated neurodegeneration in patients with PD.

Using data of the Parkinson’s Progression Markers Initiative cohort, researchers collected data of people with PD (N = 173; age, 63.3 ± 10.0 years), in which 27% were APOE ε4 carriers. They assessed how physical activity may fare in potentially modifying the negative impact of the gene variant in recently diagnosed patients.

In recent studies, exercise programs, such as Tai Chi, have been associated with slowing down disease progression, with table tennis also found to improve motor symptoms in patients with PD.

“Previous data indicate that physical activity modifies the APOE ε4 effect on the development and progression of AD,” added the study authors. “These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE ε4 and cognition in PD.“

Self-reported physical activity, measured by the Physical Activity Scale of the Elderly, was initiated in the study at 2 years after enrollment, with data of years 2, 3, and 4 included in the longitudinal analysis.

In the study, cognitive function was measured annually via Montreal Cognitive Assessment (MoCA), with dopamine transporter (DAT) imaging also performed at years 2 and 4.

At baseline, overall scores averaged 26 points, which is considered normal. By the end of the study, MoCA scores indicated that cognitive function in those with the APOE ε4 allele declined by an average of 1.33 points compared with their non-APOE ε4 allele counterparts (95% CI, –2.12 to –0.47; P = .002).

However, higher physical activity at the start of the study was associated with slower APOE ε4-related cognitive decline after 2 years by an average of 0.007 points (95% CI, 0.003 to 0.011; P = .001).

"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 Hallym University in Seoul, Korea, said in a statement.

No significant interaction was found between physical activity and the APOE ε4 allele based on changes in striatal DAT activities. Moreover, the researchers noted that as participants provided self-reported levels of physical activity, there is possibility that they may not have remembered their levels exactly.

"Additional research is needed to confirm our findings, but these results would support the use of interventions that target physical activity as a way to delay cognitive decline in people with early PD who have the APOE ε4 gene variant," said Jun.


Kim R, Park S, Yoo D, Jun JS, Jeon B. Association of physical activity and APOE genotype with longitudinal cognitive change in early PD. Neurol. Published online March 31, 2021. doi:10.1212/WNL.0000000000011852