The Association Between Body Weight Variability and Dementia and Cognitive Decline: A Systematic Review and Meta-Analysis of Cohort Studies With the GRADE Assessment.

BACKGROUND AND AIMS: The global rise in dementia, including early-onset cases, imposes a growing burden on patients and caregivers. While midlife obesity is a recognized risk factor, the role of body weight fluctuation in dementia and cognitive decline remains uncertain. This systematic review and meta-analysis examined the association between weight variability and the risk of dementia, including Alzheimer's disease, vascular dementia, and cognitive decline.

METHODS

We systematically searched PubMed, Scopus, Web of Science, and PsycINFO, supplemented by manual searches, up to July 2024. Pooled hazard ratios (HRs) were estimated through pairwise meta-analysis, with subgroup analyses conducted to explore heterogeneity. Additionally, the quality of the included studies and the certainty of the evidence were assessed using the "Risk of Bias in Non-randomized Studies of Interventions" (ROBINS-I) tool and the GRADE Tool, respectively.

RESULTS

Sixteen studies met the inclusion criteria. Compared with the lowest levels of weight fluctuation, the highest levels were associated with an increased risk of all-cause dementia (HR 1.40, 95% CI 1.29-1.52), Alzheimer's disease (HR 1.33, 95% CI 1.21-1.45), and vascular dementia (HR 1.39, 95% CI 1.16-1.67). No significant association was observed with cognitive decline. No clear source of heterogeneity was identified.

CONCLUSION

High body weight fluctuation is associated with an elevated risk of dementia, particularly Alzheimer's disease and vascular dementia. These findings highlight weight stability as a potential target for dementia prevention strategies. Further high-quality studies are warranted to clarify underlying mechanisms and long-term implications.