No abstract

Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.

A higher level of total daily physical activity is associated with a reduced risk of AD.

These data suggest that AD pathology is more likely to be clinically expressed as dementia in women than in men.

GROWING BODY OF EVIDENCE suggests that oxidative processes may be involved in the etiology of Alzheimer disease (AD). 1 Accumulated damage to lipid membranes and DNA by oxygen free radicals and reactive oxygen species is thought to disrupt normal cell functioning and lead to neuronal death. 2 Antioxidant nutrients, including vitamin E, vitamin C, and beta carotene, are among the body's natural defense mechanisms against oxidative stress. The antioxidant nutrients have been shown through animal and laboratory studies of brain tissue to decrease lipid peroxidation 3-11 and the oxidation of proteins, 12,13 inhibit the production of reactive oxygen species, 6,14,15 prevent mitochondrial dysfunction 12,16 and DNA fragmentation, 6,17 and reduce neurotoxicity, 18,19 apoptosis, 15,19-21 and neuronal death. 18,22 Few studies have examined the relation between dietary intake of antioxidant nutrients and the development of AD. Two prospective studies 23,24 that reported on the association of vitamin E and vitamin C supplement use and AD yielded conflicting results, but both had limited power to test the hypothesis, and neither had dietary information. We report on the association between incident AD and intake of antioxidant nutrients from foods and supplements in a large community study, the Chicago Health and Aging Project (CHAP).

Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP ) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer's disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43 pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia. Data came from 946 older adults with ( n = 398) and without dementia ( n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer's disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer's-type dementia formerly labelled 'pure pathologic diagnosis of Alzheimer's disease' was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer's disease and TDP-43 pathologies were associated with higher odds of clinical Alzheimer's-type dementia (odds ratio = 6.73, 95% confidence interval = 4.18, 10.85) than pathologic Alzheimer's disease alone (odds ratio = 4.62, 95% confidence interval = 2.84, 7.52). In models examining TDP-43 stage, a dose-response relationship with clinical Alzheimer's-type dementia was observed, and a significant association was observed starting at stage 2, extension beyond the amygdala. In this large sample from almost 1000 community participants, we observed that TDP-43 proteinopathy was very common, frequently mixed with pathological Alzheimer's disease, and associated with a higher likelihood of the clinical expression of clinical Alzheimer's-type dementia but only when extended beyond the amygdala.

Apolipoprotein E epsilon4 led to increased risk of AD among white subjects but not black subjects.

Declining body mass index (BMI) is associated with increased risk of incident Alzheimer disease (AD). Loss of BMI may reflect pathologic processes that contribute to the subsequent development of AD.