Public Health

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders.
• Cognitive impairment is prevalent in PD and DLB, but predictors of decline are unclear.
• This study investigates the impact of APOE genotype and sex on cognitive trajectories in PD and DLB.

Purpose of the Study:

• To analyze how risk factors, specifically APOE genotype and sex, influence memory, executive function, and language.
• To characterize cognitive decline trajectories in individuals with PD and DLB.
• To identify potential biomarkers for predicting cognitive decline in these neurodegenerative conditions.

Main Methods:

• Utilized National Alzheimer's Coordinating Center data from PD and DLB participants with baseline cognitive assessments.
• Employed linear mixed-effects models to analyze factor scores for memory, executive function, and language.
• Included predictors such as sex, race, age, APOE genotype, education, and time since diagnosis, with a focus on the post-mild cognitive impairment (MCI) phase.

Main Results:

• A faster rate of cognitive decline was observed post-MCI diagnosis across memory, executive function, and language domains.
• APOE genotype significantly modified memory decline, with individuals carrying 1-2 ε4 alleles declining 0.05 SD/year faster post-MCI.
• Sex did not significantly modify the rate of cognitive decline post-MCI.

Conclusions:

• APOE genotype is a significant predictor of accelerated memory decline in PD and DLB patients following an MCI diagnosis.
• The findings suggest APOE genotype's utility in prognostication for PD/DLB.
• This research supports a personalized medicine approach for managing cognitive decline in PD and DLB.