Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study.

BACKGROUND: Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain. OBJECTIVE: Our aim was to determine whether serum folate is inversely associated with the severity of atrophy of the neocortex. DESIGN: Nutrients, lipoproteins, and nutritional markers were measured in the blood of 30 participants in the Nun Study from one convent who later died when they were 78-101 y old (mean: 91 y). At autopsy, several neuropathologic indicators of Alzheimer disease were determined, including the degree of atrophy of 3 lobes of the neocortex (frontal, temporal, and parietal) and the number of neocortical Alzheimer disease lesions (ie, senile plaques and neurofibrillary tangles) as assessed by a neuropathologist. RESULTS: The correlation between serum folate and the severity of atrophy of the neocortex was -0.40 (P = 0.03). Among a subset of 15 participants with significant numbers of Alzheimer disease lesions in the neocortex, the correlation between folate and atrophy was -0.80 (P = 0.0006). Atrophy may be specific to low folate because none of the 18 other nutrients, lipoproteins, or nutritional markers measured in the blood had significant negative correlations with atrophy. CONCLUSIONS: Among elderly Catholic sisters who lived in one convent, ate from the same kitchen, and were highly comparable for a wide range of environmental and lifestyle factors, low serum folate was strongly associated with atrophy of the cerebral cortex. Definitive evidence for this relation and its temporal sequence awaits the findings of other studies.

Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

Weight change and physical function in older women: findings from the Nun Study.

OBJECTIVE: To investigate the association between change in weight and decline in physical function in older women. DESIGN: Longitudinal study of a defined population of Catholic sisters (nuns) whose weight and function were assessed twice, an average of 584 days apart. SETTING: Unique life communities (convents) located throughout the United States. PARTICIPANTS: 475 Catholic sisters who were 75 to 99 years of age (M = 82.1, SD = 4.8) and were independent in at least one Activity of Daily Living (ADL) at the first assessment of weight and function. INTERVENTIONS: None. MEASUREMENTS: At each assessment, weight, ADLs, and cognitive function were evaluated as part of the Nun Study--a longitudinal study of aging and Alzheimer's disease. Annual percent weight change was calculated using weights from the two assessments, as well as the number of days that elapsed between assessments. RESULTS: Mean weight at first assessment was 140 pounds (range 78 to 232, SD = 27). The mean annual percent weight change was 0.1% (range 22% loss to 16% gain, SD = 3.8). Age- and initial weight-adjusted findings indicated that those participants with an annual percent weight loss of 3% or greater had 2.7 to 3.9 times the risk of becoming dependent in each ADL, compared to the sisters with no weight change. The elevated risk persisted in those who were mentally intact or were independent in their eating habits. CONCLUSION: Monitoring of weight may be an easy and inexpensive method of identifying older individuals at increased risk of disability.

Serum zinc, senile plaques, and neurofibrillary tangles: findings from the Nun Study.

Zinc appears to have a role in binding amyloid precursor protein in vitro, but it is not known whether zinc plays a role in senile plaque formation in vivo in humans. Serum zinc concentrations were available from 12 sisters who died in the Nun Study, a longitudinal study of aging and Alzheimer's disease. Fasting serum zinc concentrations, determined approximately 1 year before death, showed moderate to strong negative correlations with senile plaque counts in seven brain regions. In all brain regions combined, the age-adjusted negative correlations with serum zinc were statistically significant for total senile plaques and diffuse plaques, and suggestive for neuritic plaques. Thus serum zinc in the normal range may be associated with low senile plaque counts in the elderly.