Genetic background and multidomain interventions in mild cognitive impairment

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Dementia prevalence is rising, necessitating effective prevention strategies.
• Multidomain interventions show partial efficacy, but identifying responders is key.
• Genetic background's role in intervention effectiveness requires further investigation.

Purpose of the Study:

• To investigate the association between genetic background and the effectiveness of multidomain interventions for dementia prevention.
• To stratify participants based on polygenic risk scores (PRSs) for Alzheimer's disease.
• To identify genetic variants influencing intervention outcomes.

Main Methods:

• Utilized data from the Japan-Multimodal Intervention Trial for the Prevention of Dementia (J-MINT).
• Analyzed 289 participants with mild cognitive impairment undergoing a 18-month multidomain intervention (exercise, nutrition, cognitive, social, vascular).
• Stratified participants by Japanese Alzheimer's disease polygenic risk scores (PRSs) and age; conducted whole-genome sequencing variant analysis.

Main Results:

• In participants aged <75, those with high PRS showed significant cognitive improvement at 6 months.
• No significant cognitive improvement differences were observed in participants aged ≥75, regardless of PRS.
• Two loci (ID3 and LMO1) showed suggestive associations with reduced intervention effectiveness.

Conclusions:

• Polygenic risk scores (PRSs) can predict cognitive improvement in response to multidomain interventions.
• Identified specific genetic variants potentially modulating intervention efficacy.
• Findings support the development of personalized dementia prevention strategies based on genetic profiles.