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Background <p>Multidomain lifestyle interventions have shown effectiveness in preventing dementia, but identifying high-risk groups most likely to benefit remains unclear.</p> Methods <p>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 <i>APOE</i> ε4 status using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total index as the primary outcome.</p> Results <p>Both intervention and control groups showed cognitive improvement over 24&#xa0;weeks, with greater gains in the intervention arm. Relative intervention efficacy (RIE) increased with higher genetic risk, being most pronounced among <i>APOE</i> ε4 carriers and individuals with high PRS. When both factors were considered jointly, <i>APOE</i> ε4 carriers with high PRS exhibited the largest RIE (β = 7.54, SE = 2.59, <i>p</i> = 0.005), driven by markedly greater improvement in the intervention group. The secondary outcomes did not show as consistent results as RBANS total index.</p> Discussion <p>These findings suggest that MCI individuals who are <i>APOE</i> ε4 carriers with high PRS may benefit most from multidomain interventions. These results support the complementary use of PRS and <i>APOE</i> status for identifying high-risk subgroups most likely to benefit from multidomain interventions.</p> Trial registration <p>ClinicalTrials.gov identifier: NCT05023057. Registered on 26 August 2021.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月12日

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  • Jiyun Hwang,
  • So Young Moon,
  • Harim Lee,
  • Jaejin Lee,
  • Yoo Kyoung Park,
  • Jee Hyang Jeong,
  • Chang Hyung Hong,
  • Jiwoo Jung,
  • Hae Ri Na,
  • Soo Hyun Cho,
  • Joohon Sung,
  • Soo Ji Lee,
  • Seong Hye Choi

摘要

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 ε4 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 ε4 carriers and individuals with high PRS. When both factors were considered jointly, APOE ε4 carriers with high PRS exhibited the largest RIE (β = 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 ε4 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.

Trial registration

ClinicalTrials.gov identifier: NCT05023057. Registered on 26 August 2021.