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Martha Clare Morris, ScD; Denis A. Evans, MD; Julia L. Bienias, ScD; Christine C. Tangney, PhD; Liesi E. Hebert, ScD; Paul A. Scherr, PhD, ScD; Julie A. Schneider, MD

Arch Neurol. 2005;62:641-645.

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 more than 400 µg/d compared with nonusers ( = –.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.

Author Affiliations: Rush Institute for Healthy Aging (Drs Morris, Evans, Bienias, and Hebert), Departments of Internal Medicine (Drs Morris, Evans, Bienias, and Hebert), Preventive Medicine (Dr Morris), and Clinical Nutrition (Dr Tangney), and Rush Alzheimer’s Disease Center (Dr Schneider), Rush University Medical Center, Chicago, Ill; and Division of Adult and Community Health, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Scherr).

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