5. Lastly, we shall discuss biomarkers, starting with imaging and moving MLN8237 onto telomeres, plasma measures, cerebrospinal fluid (CSF) measures, and inflammatory biomarkers. 1A. Causes of cognitive decline in older persons The three most common forms of dementia are AD, Lewy body disease (LBD), and vascular dementia (VaD) [9] and all contribute to cognitive decline and brain atrophy. Noting that mixed dementia (having overlapping contributions) is common, Dickson and colleagues [9] reported that, in the Florida Brain Bank, the most frequent pathologies contributing to dementia were AD (77%), followed by LBD (26%), and then VaD (18%). In support of this finding is a paper by the Rush group [10], which reported the pathological and cognitive findings from two prospective community-based studies; in 652 patients who had come to autopsy, the three pathologies above were significantly associated with the cognitive measures.

Compelling studies show that cognitively normal older persons frequently have AD pathology. In 2,661 autopsy cases, Braak and Braak [11] reported that 27% of persons over 70 and 39% over 75 have significant amyloid (stages B and C) and tau (greater than stage III) pathology. In support of this observation, amyloid A?? imaging in cognitively normal older individuals revealed that 21% [12] to 30% [13] had positive scans. A recent study [14] indicates that the prevalence curve by age for positive Pittsburgh compound-B (PIB) scans in cognitively normal persons overlies the prevalence of amyloid plaque measures from Braak and Braak’s [11] autopsy study in nondemented persons.

Very interestingly, this curve parallels the AD prevalence curve but is 15 years earlier than the AD curve. This 15-year window may be the opportunity to prevent AD with interventions such as exercise. Cilengitide We also point out that, in the Rush community-based study [10], AD pathology, vascular disease, and Lewy body pathology are common in cognitively normal persons. 1B. Could exercise be a broad-spectrum intervention? It has long been known that exercise may have many health benefits. Studies suggest that it decreases mortality [15], improves cardiovascular function [16], enhances cognitive functioning [17,18], decreases coronary heart disease [19], decreases fall risk in older persons [20], and improves depression [21].

Barnes selleck bio and colleagues [22], in a review, summarized the effects of exercise on obesity, vascular disease, hypertension, diabetes, and inflammation and how all of these factors may be protective of the brain. It is possible that exercise helps protect against the three most common dementia pathologies. In an AD transgenic mouse model, Lazarov and colleagues [23] showed that environmental enrichment, including an exercise wheel, decreased A?? brain deposits.