Certain Genes May Speed Up Memory Loss in Parkinson’s Disease Patients With Low Risk of Alzheimer’s

Lasse Pihlstrøm, PhD

A new study found that a specific genetic factor, called the lysosomal pathway, might lead to faster memory and thinking problems in people with Parkinson’s disease who are at low risk for Alzheimer disease.¹ This highlights how genes and brain changes in Parkinson’s are connected, and points to the importance of lysosomal gene variations in cognitive decline.

Researchers looked at data from two groups of Parkinson’s patients: 374 patients from the Parkinson’s Progression Markers Initiative (PPMI) and 777 patients from the Parkinson’s Disease Biomarker Program (PDBM). In both groups, they found that patients with a higher number of certain lysosomal gene variants had quicker memory and thinking decline if they were at low risk for Alzheimer disease.

Key Points:

• Lysosomal gene changes may be linked to faster thinking and memory decline in Parkinson’s patients with low Alzheimer risk.
• These findings could help doctors predict who might experience faster cognitive decline in Parkinson’s.
• More research is needed to confirm these results and explore possible new treatments based on this genetic information.

Lasse Pihlstrøm, PhD, senior researcher in department of neurology at Oslo University Hospital in Norway, and his team from Oslo University Hospital in Norway found that these lysosomal gene variants increased the risk of faster memory loss in Parkinson’s patients who were not likely to develop Alzheimer’s. They suggested that understanding this genetic influence could improve how we identify and treat cognitive problems in Parkinson’s.

The study, published in Movement Disorders, used two methods to study the connection between lysosomal gene scores and the time it took for patients to experience significant memory decline. The researchers used information from spinal fluid samples to help distinguish between patients with and without signs of Alzheimer’s. Their analysis showed that in Parkinson’s patients with low Alzheimer’s risk, having higher lysosomal gene scores was linked to a shorter time to memory decline.

Even when excluding a gene called GBA1, which is known to affect Parkinson’s, the link between lysosomal gene variants and faster memory decline remained strong in both patient groups. This suggests that other lysosomal gene changes also play a role in cognitive decline in Parkinson’s patients who aren’t at high risk for Alzheimer’s.

While the study had some limitations, including the number of patients studied, the results were consistent across both patient groups. Researchers noted that further studies with larger patient groups and more detailed assessments of memory and thinking are needed to confirm and expand on these findings. They hope that by better understanding these genetic risks, doctors will be able to personalize treatment and identify new therapies to help slow memory decline in Parkinson’s patients.

An original version of this article was published on sister site Neurology Live.

REFERENCES
^{1. Tunold JA, Tan MMX, Toft M, Ross O, van de Berg WDJ, Pihlstrøm L. Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk. Mov Disord. 2024;39(3):596-601. doi:10.1002/mds.29698}