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Multidomain lifestyle interventions combined with pharmacological or nutraceutical approaches may improve cognition in individuals across the Alzheimer's disease continuum.

A systematic review of 12 randomized controlled trials found that combining multidomain lifestyle interventions (2-7 domains including physical exercise, cognitive training, dietary guidance, social activities, sleep hygiene, cardiovascular/metabolic risk management, psychoeducation or stress management) with pharmacological components (e.g., Omega-3, Tramiprosate, vitamin D, BBH-1001, epigallocatechin gallate, Souvenaid, metformin) may effectively improve cognition. Seven trials targeted participants with prodromal AD, MCI, or early dementia, while five focused on at-risk individuals or those with subjective cognitive decline, with two studies enriching populations for APOE-ε4 carriers.

Last updated: Aug 26, 2026•1 RCTs•📖 Read as article →

Evidence Score

Evidence Score42/100
Human RCT★★☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Risk reduction and precision prevention across the Alzheimer's disease continuum: a systematic review of clinical trials combining multidomain lifestyle interventions and pharmacological or nutraceutical approaches.

observational

Bereczki E, Mangialasche F, Barbera M, Padilla P, Hara Y, Fillit H, Solomon A, Kivipelto M · The journal of prevention of Alzheimer's disease (2025)

Participants: N/A
Duration: At least 6 months
Intervention: Combination of multidomain lifestyle interventions (≥2 domains) and pharmacological or nutraceutical components (e.g., Omega-3, Tramiprosate, vitamin D, BBH-1001, epigallocatechin gallate, Souvenaid, metformin) for at least 6 months.
Outcome: Cognitive or dementia-related measures (e.g., cognition improvement).
Effect Size: N/A
Population: Individuals across the Alzheimer's disease continuum, including cognitively normal at-risk individuals, those with subjective cognitive decline, mild cognitive impairment, or prodromal AD.

Result:

PubMed: 41145344DOI: 10.1016/j.tjpad.2025.100367

Mechanism Graph

Multidomain lifestyle interventions target multiple risk factors and disease mechanisms
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Pharmacological components add complementary effects
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Tailored and early implementation optimizes intervention timing
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Result: Potential improvement in cognition

Limitations

  • ⚠Only 12 RCTs were identified, limiting generalizability
  • ⚠Further refinement of RCT methodology is needed to better align with the multifaceted nature of dementia prevention

Frequently Asked Questions

What types of lifestyle domains were included in the interventions?▼

The interventions included 2 to 7 lifestyle domains such as physical exercise, cognitive training, dietary guidance, social activities, sleep hygiene, cardiovascular/metabolic risk management, and psychoeducation or stress management.

Which pharmacological components were combined with lifestyle interventions?▼

Pharmacological components included Omega-3, Tramiprosate, vitamin D, BBH-1001, epigallocatechin gallate, Souvenaid, and metformin.

Who was the target population for these combination trials?▼

The target population included individuals across the Alzheimer's disease continuum: cognitively normal at-risk individuals, those with subjective cognitive decline, mild cognitive impairment, or prodromal AD.

What was the minimum duration of the interventions in the reviewed trials?▼

All included interventions lasted at least 6 months.

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References

  1. 1.Bereczki E, Mangialasche F, Barbera M, Padilla P, Hara Y, Fillit H, Solomon A, Kivipelto M. "Risk reduction and precision prevention across the Alzheimer's disease continuum: a systematic review of clinical trials combining multidomain lifestyle interventions and pharmacological or nutraceutical approaches.." The journal of prevention of Alzheimer's disease, 2025. PMID: 41145344 DOI: 10.1016/j.tjpad.2025.100367
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.