Serum folate and risk of disabling dementia: a community-based nested case–control study

Purpose The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia).Methods We performed a nested case–control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40–84 years at the baseline period of 1984–2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models.Results After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51–0.99), 0.76 (0.54–1.06), 0.70 (0.49–1.00), and 0.62 (0.43–0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke.Conclusion In this nested case–control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals.