Elevated serum total homocysteine (tHcy) is an established risk factor for cardiovascular disease. Its role in dementia is still controversial, and no study has examined the role of midlife tHcy, or reports longer than 8 years of follow-up. We examined the relation between midlife tHcy and late-life dementia in women followed for 35 years. The Prospective Population Study of Women in Gothenburg began in 1968-1969, comprising a representative population of women aged 38-60 years. Four extensive follow-ups were conducted by 2003. Serum samples from 1968 to 1969 were analysed for tHcy in 1368 women. In total, 151 women developed dementia. The highest tHcy tertile was related to a hazard ratio of 1.7 (95% CI 1.1-2.6) for developing any dementia, 2.1 (95% CI 1.2-3.7, n=100) for AD and 2.4 (95% CI 1.3-4.7, n=68) for AD without cerebrovascular disease. Kaplan-Meier plots showed divergence with respect to dementia after 22 years of follow-up. In conclusion, high homocysteine in midlife is an independent risk factor for the development of late-life Alzheimer dementia in women.
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