Objective: To explore the associations of low serum levels of vitamin B₁₂ and folate with AD occurrence. Methods: A population-based longitudinal study in Sweden, the Kungsholmen Project. A random sample of 370 nondemented persons, aged 75 years and older and not treated with B₁₂ and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B₁₂ (≤150 and ≤250 pmol/L) and folate (≤10 and ≤12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. Results: When using B₁₂ ≤150pmol/L and folate ≤10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B₁₂or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B₁₂or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B₁₂ ≤250 pmol/L and folate ≤12 nmol/L. Conclusions: This study suggests that vitamin B₁₂ and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B₁₂ and folate concentration in the elderly may be relevant for prevention of AD.

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