Underweight is associated with increased risk of all-cause dementia in older adults with vascular risk factors, independent of brain atrophy and small vessel disease

BackgroundUnderweight, defined as a body mass index (BMI) < 18.5 kg/m2, has been associated with increased risk of dementia in older adults. However, whether this association reflects a causal relationship remains unclear.ObjectiveTo examine the association between low BMI and dementia, independent of brain magnetic resonance imaging findings.MethodsWe analyzed data from patients aged ≥ 65 years with vascular risk factors enrolled in a Japanese observational registry. Patients were categorized by BMI as underweight (<18.5 kg/m²), normal weight (18.5-24.9 kg/m²), or overweight (≥25.0 kg/m²). The outcomes were all-cause dementia and Alzheimer's disease (AD) dementia.ResultsA total of 607 patients (median age, 74 years) were included: 58 underweight, 389 normal weight, and 160 overweight. During a median follow-up of 4.7 years, 39 patients developed dementia and 30 developed AD dementia. Kaplan-Meier analysis showed that underweight group had a significantly higher incidence of all-cause dementia (p = 0.002) and AD dementia (p = 0.009) compared with the other groups. Cox regression hazard analysis adjusted for age and sex revealed that underweight had a higher risk of all-cause dementia (hazard ratio, 3.38; 95% confidence interval, 1.49-7.67) compared with normal weight. In exploratory analysis, the association between underweight and all-cause dementia remained significant after adjustment for additional confounders, medial temporal atrophy, and white matter hyperintensities.ConclusionsUnderweight in older adults was associated with increased risk of all-cause dementia independent of age, sex, confounding factors, brain atrophy and white matter hyperintensities. These findings warrant confirmation in larger cohorts.Clinical Trial RegistrationUMIN000026671.