Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment

초록

Background: Multidomain lifestyle interventions have shown effectiveness in preventing dementia, but identifying high-risk groups most likely to benefit remains unclear. Methods: We re-evaluated the SUPERBRAIN-MEET multidomain intervention study in mild cognitive impairment (MCI) patients, incorporating polygenic risk scores (PRS) for Alzheimer's disease and APOE epsilon 4 status using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total index as the primary outcome. Results: Both intervention and control groups showed cognitive improvement over 24 weeks, with greater gains in the intervention arm. Relative intervention efficacy (RIE) increased with higher genetic risk, being most pronounced among APOE epsilon 4 carriers and individuals with high PRS. When both factors were considered jointly, APOE epsilon 4 carriers with high PRS exhibited the largest RIE (beta = 7.54, SE = 2.59, p = 0.005), driven by markedly greater improvement in the intervention group. The secondary outcomes did not show as consistent results as RBANS total index. Discussion: These findings suggest that MCI individuals who are APOE epsilon 4 carriers with high PRS may benefit most from multidomain interventions. These results support the complementary use of PRS and APOE status for identifying high-risk subgroups most likely to benefit from multidomain interventions.

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