Apolipoprotein E4, physical activity interacts to delay Parkinson’s disease cognitive decline

An interaction between gene and physical activity can affect cognitive decline in early Parkinson’s disease (PD) patients who are carriers of apolipoprotein E4. This is evident from study results discussed in a letter published in Neurology.

This study was motivated by observational data that linked physical activity with a decreased risk of Parkinson’s disease and a decrease in the progression of cognitive decline. Previous data indicated that mice with PD carrying apolipoprotein E4 had increased swimming speeds and exploration times after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

To examine the relationship between activity and PD, Kim et al. studied patients with early Parkinson’s disease for self-reported physical activity and cognitive decline over a 2-year period. The study researchers observed that carriers of apolipoprotein E4 had a greater decline in cognition than carriers of non-apolipoprotein E4.

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However, carriers of apolipoprotein E4 who experienced high levels of physical activity appeared to have cognitive decline, which was moderated by their physical activity.

The authors of that letter speculated that these results might suggest that physical activity might be a valuable tool in delaying the progression of Parkinson’s disease.

Additional studies are needed to determine whether exercise can be incorporated into personalized treatment plans. These future studies should include more comprehensive assessments of cognition, such as quantifying cognitive violations and monitoring physical activity through wearable devices. More extensive genetic analysis is needed to determine whether additional genetic mediators are involved in this apparent gene-physical activity interaction.

If these observations are repeated among other independent cohorts of patients with Parkinson’s disease, it may be possible to mitigate the cognitive decline associated with other neurodegenerative disorders associated with physical activity. Expanding the study of physical activity in other neurodegenerative diseases should be considered.

The letter’s authors concluded that this study may have uncovered a promising new avenue for personalized treatment plans that aim to delay cognitive decline in people with Parkinson’s disease.


Raber J, Darweesh SKL, Savica R. Physical activity may decrease apolipoprotein E4-associated cognitive decline in Parkinson’s disease. Neurology. Published online March 31, 2021. doi: 10.1212 / WNL.0000000000011851

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