Relation of higher folate intake to lower risk of Alzheimer disease in the elderly
Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R.;
Commented by , 30 Jan 2007
Aim of the study
Relate intake of folate and vitamins B6 and B12 to risk of Alzheimer disease (AD) in subjects predominantly of Caribbean Hispanic and African American origin living in northern Manhattan, New York.
Method
Cohort of 965 persons age 65 years or older without dementia at baseline followed longitudinally for a mean ± SD period of 6.1 ± 3.3 person-years. These subjects were selected from a random sampling of Medicare recipients. Total dietary and supplement intake of folate, B6, B12 and kilocalories intake were estimated from responses to a 61-item semiquantitative food frequency questionnaire at baseline.
Energy-adjusted intake of folate, B6 and B12 were related to incident AD using the Cox proportional hazards regression model, with adjustment for age, gender, education, ethnic group, apoE genotype, diabetes mellitus, hypertension, current smoking, heart disease, stroke. The diagnosis of AD was made by consensus of neurologists, a psychiatrist and neuropsychologists using standard criteria.
Results
There were 192 cases of incident AD. The highest quartile of total folate intake, after adjustment for B6 and B12 intake, was significantly related to a lower risk of AD (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.02 for trend). The overall energy-adjusted folate intake was almost statistically lower in the group with incident AD vs non-demented subjects (383.8 vs 407.5 µg; P=0.9).
Professor Gauthier's comments
There is a hypothesis that higher intake of folate, B6 and B12 may decrease the risk of AD through the lowering of homocysteine levels, homocysteine potentiating the effects of amyloid-β on calcium influx and apoptosis. This prospective obeservational epidemiological study in the USA suggest that this may be true for folate.
This finding should be put in the context of fortification of grain with folate in that country since 1997, whereas the baseline data on nutrition was collected between 1992 and 1994. No such fortification is used in Europe currently, leading to lower plasma levels of folate in Europe compared to North-America, interfering with acceptable laboratory "normal" levels in multinational drug trials.
Randomized clinical trials are under way to confirm the validity of folate supplements as a mean of primary prevention for AD. Until these results are available, enrichment of diet with folate-rich vegetables should be encouraged!