Cognitive and motor functioning in elderly glucocerebrosidase mutation carriers.

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Glucocerebrosidase (GBA) gene mutations are a known risk factor for Parkinson's disease and dementia with Lewy bodies.
• The penetrance of GBA mutations for these neurodegenerative diseases is low in heterozygous carriers.
• Understanding the impact of GBA mutations on cognitive and motor function in aging populations is crucial.

Purpose of the Study:

• To investigate the relationship between heterozygous GBA mutation status and cognitive and motor functioning in non-demented, non-Parkinsonian community-dwelling older adults.
• To assess the longitudinal effects of GBA mutations on specific cognitive domains and motor performance.
• To determine the extent of cognitive and motor decline associated with carrying a single GBA mutation.

Main Methods:

• Longitudinal study of 736 community-dwelling older adults (age ≥70 years) over an average of 6 years.
• Analysis of 28 participants with a single GBA mutation (primarily N370S) compared to non-carriers.
• Linear mixed effects models used to assess the effect of mutation status on cognitive and motor function, including verbal memory (Free and Cued Selective Reminding Test).

Main Results:

• Heterozygous GBA mutation carriers exhibited a significantly greater decline in verbal memory over time (p < 0.05).
• No significant differences were observed in motor function between carriers and non-carriers.
• No differences were found in other cognitive domains assessed.

Conclusions:

• Harboring a single GBA mutation is associated with an accelerated decline in verbal memory in aging individuals.
• The overall burden of a single GBA mutation on cognitive and motor function appears limited in this cohort.
• Further research is warranted to fully elucidate the long-term neurological implications of GBA mutations in aging populations.