Background: Deficiencies in folate and vitamin B₁₂ have been associated with neurodegenerative disease.

Objective: To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B₁₂.

Design: Prospective study performed from 1993 to 2002.

Setting: Geographically defined biracial community in Chicago, Ill.

Participants: A total of 3718 residents, 65 years and older, who completed 2 to 3 cognitive assessments and a food frequency questionnaire.

Main outcome measure: Change in cognitive function measured at baseline and 3-year and 6-year follow-ups, using the average z score of 4 tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test.

Results: High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors. The rate of cognitive decline among persons in the top fifth of total folate intake (median, 742 μg/d) was more than twice that of those in the lowest fifth of intake (median, 186 μg/d), a statistically significant difference of 0.02 standardized unit per year ( p = .002). A faster rate of cognitive decline was also associated with high folate intake from food ( p for trend = .04) and with folate vitamin supplementation of> 400 μg/d compared with nonusers (β = -.03, p < .001). High total B₁₂ intake was associated with slower cognitive decline only among the oldest participants.

Conclusions: High intake of folate may be associated with cognitive decline in older persons. These unexpected findings call for further study of the cognitive implications of high levels of dietary folate in older populations. ( Arch Neurol. 2005;62:641-645.).