A total of 161 cases of incident Alzheimer’s disease were diagnosed during a median follow-up of 3.9 years among the 1,041 clinically evaluated CHAP participants. Folate intake ranged from 89.7 to 1660 µg/d, with a median intake level of 338 µg/d, or about the equivalent of the recommended dietary allowance of 400 µg/d. Vitamin B-12 intake ranged from 0.53 to 127.7 µg/d, and vitamin B-6 ranged from 0.58 to 100.9 mg/d. High total intakes of all three B-vitamins were associated with a more favorable risk profile for prevention of Alzheimer’s disease including younger age, white race, higher educational level, greater participation in cognitive activities, not having the APOE-ε4 allele, and higher intakes of vitamin E and niacin, which were protectively associated with incident Alzheimer’s disease in previous CHAP studies [23
] The only case of association with a negative risk factor was higher intake of saturated fat among persons with high intake of vitamin B-12.
Intake of folate from food and supplements was not associated with the risk of developing Alzheimer’s disease. The age-adjusted odds ratio of 0.5 for persons in the top quintile of intake (median of 752.7 µg/d) compared with persons in the lowest quintile of intake (median, 202.8 µg/d) was not statistically significant. () The odds ratio for the fifth quintile was modified to 0.7 with additional adjustment for sex, race, education, cognitive activities, and APOE-ε4 allele status. This was further substantially modified to an increased odds ratio of 1.6 in analyses that accounted for confounding by dietary intakes of vitamin E and total niacin, two dietary factors that were found previously to be strong protective factors for Alzheimer’s disease in the CHAP study population, and were also linearly associated with folate intake (see ). The estimated odds ratios did not change in models that further controlled for intakes of saturated and trans fats, or of the ratio of polyunsaturated to saturated fat intake. (data not shown.) A similar pattern of non-significant but increasing odds ratios was observed for folate intake from food intake only, after adjustments for important dietary and non-dietary risk factors ().
Odds ratios for incident Alzheimer’s disease by quintiles of intake of folate, vitamin B-12, and vitamin B-6 among 1,041 persons after 4.0 years of follow-up, Chicago Health and Aging Project, 1993–2002
Baseline characteristics* of 1,041 participants of the Chicago Health and Aging Project
Persons in the highest quintile of total vitamin B-12 intake (median intake, 20.6 µg/d) had a marginally significant decreased risk of Alzheimer’s disease compared with persons in the lowest quintile of intake (median 3.1 µg/d) in the age-adjusted model (). The effect estimate of 0.4 was not modified with adjustment for the important non-dietary risk factors, however, with further adjustment for dietary intakes of vitamin E and total niacin, the odds ratio for the fifth quintile was increased to 0.6 and no longer statistically significant.
An apparent protective, marginally significant, association of high vitamin B-12 intake from food sources in the basic-adjusted model was due to confounding by intakes of dietary vitamin E and total niacin as evidenced by an increase in the odds ratio for the fifth quintile to 1.0.
Total and food intakes of vitamin B-6 had similar patterns of association with Alzheimer’s disease, with apparent linear associations in the age- and basic-adjusted models that were strongly modified and no longer statistically significant once the contribution of vitamin E and niacin were accounted for in the analysis ().
In further analyses, we re-analyzed the data after excluding 18 of the Alzheimer’s disease cases who had a co-existing condition that could cause the dementia. However, the estimated odds ratios for the fifth versus first quintiles were: 2.1 (95% CI: 0.5, 8.1) for total folate, 0.6 (95% CI: 0.2, 1.6) for total vitamin B-12, and 0.8 (95% CI: 0.2, 3.1) for total vitamin B-6.
We also examined the data for potential modifications in the vitamin associations with Alzheimer’s disease by age, sex, race, and APOE-ε4 genotype, but there was no evidence of statistical interaction with dietary intakes of folate, vitamin B-12, or vitamin B-6. There was also no statistical interaction among dietary intakes of the three B-vitamins on Alzheimer’s disease.
In secondary analyses, we investigated whether the negative findings for intakes of folate, vitamin B-12, or vitamin B-6 could be due to changes in dietary consumption patterns among persons who developed Alzheimer’s disease, or to poor recall of diet or supplement use among persons with poor cognitive function. First, we reanalyzed the fully adjusted models for the three B-vitamins after including a variable of the time period between FFQ completion and clinical evaluation for incident Alzheimer’s disease, however, there were no material differences in the estimated odds ratios for the quintiles of intake. For example, the odds ratios for the fifth versus first quintiles of intake were: 1.6 for folate, 0.6 for vitamin B-12, and 0.7 for vitamin B-6. And finally, when we deleted 50 persons from the analysis who had poor cognitive performance at the baseline, the fully-adjusted odds ratios for the fifth quintiles of intake were: 1.3 for folate, 0.5 for vitamin B-12, and 0.9 for vitamin B-6.