Body weight variability associated with increased dementia risk in meta-analysis of cohort studies

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.