Highlight
- Combination of physical exercise and cognitive training yields the most significant improvement in global cognition among cognitively unimpaired older adults.
- Both single-domain (physical exercise, cognitive training) and multidomain (diet, exercise, cognitive training, health education) interventions improve cognition compared to health education or controls.
- Increasing the number of intervention domains does not necessarily result in greater cognitive benefits, indicating the importance of intervention quality and synergy over quantity.
- High risk of bias and publication bias in included trials warrant cautious interpretation and highlight the need for rigorous future research to refine preventive strategies.
Study Background
Preventing cognitive decline in aging populations represents a pressing public health priority due to the rising prevalence of dementia and related disorders. Cognitive impairment leads to substantial individual morbidity, caregiver burden, and healthcare costs worldwide. Despite advances in symptomatic treatments, no definitive cure for dementia exists, underscoring the importance of preventive interventions initiated during the cognitively unimpaired stage in older adults. Lifestyle factors such as physical activity, diet, cognitive engagement, and social interactions have all been implicated in cognitive aging trajectories. Multidomain lifestyle interventions targeting several risk factors simultaneously have shown promising effects in slowing cognitive deterioration. However, the optimal combination and relative efficacy of single versus multidomain interventions remain unclear, limiting evidence-based guidelines for clinical practice and public health policy.
Study Design
This systematic review and network meta-analysis synthesized evidence from randomized controlled trials (RCTs) assessing lifestyle interventions aimed at preventing cognitive decline among older adults without baseline cognitive impairment. The review followed a preregistered protocol in PROSPERO (CRD42024601975) and screened PubMed and Embase databases up to May 7, 2024.
Eligible trials included interventions targeting one or more of the following domains: diet, physical exercise, cognitive training, social activity, and health education. Both single-domain and multidomain interventions were analyzed. The primary outcome was change in global cognition, measured by validated neuropsychological assessments. Comparator groups included health education, active control interventions, or no intervention.
A random-effects network meta-analysis framework was applied to compare and rank the efficacies of these interventions, with standardised mean differences (SMD) and 95% confidence intervals (CIs) reported. Subgroup analyses explored potential variation by age and intervention duration. Quality assessment employed the Cochrane Risk of Bias 2 tool, and publication bias was assessed via funnel plot asymmetry.
Key Findings
From 10,200 retrieved citations and 1,183 full-text evaluations, 109 eligible RCTs involving 23,010 participants (median age 70.1 years, 65% female) were included. Comparative analyses against health education as the reference group revealed several notable findings:
- The combination of physical exercise and cognitive training achieved the largest benefit on global cognition (SMD 0.26; 95% CI 0.10–0.42; p=0.0011).
- Cognitive training alone also showed significant improvement (SMD 0.21; 95% CI 0.08–0.33; p=0.00092).
- Comprehensive multidomain interventions including diet, physical exercise, cognitive training, and health education had smaller but significant effects (SMD 0.14; 95% CI 0.02–0.27; p=0.028).
- Physical exercise alone was effective as well (SMD 0.14; 95% CI 0.05–0.22; p=0.0014).
Similar effect sizes and statistical significance were observed when using active control and no intervention groups as comparators, reinforcing the robustness of these findings. However, interventions focusing solely on diet or social activity did not consistently demonstrate significant cognitive benefits.
Risk of bias was rated as high in 40% of studies, primarily due to issues such as lack of blinding or incomplete outcome data. Funnel plot analysis suggested the presence of publication bias, especially in trials comparing interventions with health education.
Expert Commentary
This comprehensive network meta-analysis provides critical insight into the comparative effectiveness of lifestyle interventions for cognitive health in older adults without baseline impairment. The superiority of combined physical and cognitive training interventions aligns with mechanistic evidence supporting synergistic effects on neuroplasticity, cerebral blood flow, and cognitive reserve enhancement.
Nonetheless, the data caution against assuming a ‘‘more is better’’ approach, as increasing the number of combined intervention domains did not proportionally increase cognitive benefits. This highlights the importance of selecting and tailoring interventions based on individual risk profiles, feasibility, and adherence potential.
The predominance of methodological limitations such as publication bias and high risk of bias in a substantial proportion of included trials signals the need for higher quality RCTs with rigorous designs, standardized cognitive outcomes, and longer follow-up periods to ascertain sustainability of effects.
Current dementia preventive guidelines increasingly advocate for multidomain lifestyle strategies; this study refines these recommendations by emphasizing the particularly strong role of physical exercise paired with cognitive training. Incorporation of these findings into clinical and community health programs could enhance early preventive efforts.
Conclusion
In cognitively unimpaired older adults, certain lifestyle interventions—especially the combination of physical exercise and cognitive training—demonstrate clear efficacy in improving global cognitive function. Single-domain interventions also offer benefit, but the incremental advantage of multidomain approaches depends on the specific combination rather than the sheer number of domains targeted.
Public health initiatives and clinical practice should prioritize these evidence-based interventions to delay or prevent cognitive decline, potentially reducing dementia incidence over time. Future research should focus on identifying optimal intervention combinations, durations, and target populations, while addressing methodological shortcomings in trial design.
Funding and ClinicalTrials.gov
This study did not receive external funding. The protocol is registered in PROSPERO (CRD42024601975). No specific clinical trials registration was associated with this meta-analysis.
References
Mendes AJ, Ribaldi F, Sayin O, Khachvani G, Mulargia R, Volpara G, Remoli G, Nencha U, Gianonni-Luza S, Cappa S, Frisoni GB. Single-domain and multidomain lifestyle interventions for the prevention of cognitive decline in older adults who are cognitively unimpaired: a systematic review and network meta-analysis. Lancet Healthy Longev. 2025 Sep;6(9):100762. doi: 10.1016/j.lanhl.2025.100762. Epub 2025 Sep 25. PMID: 41016407.
