High Cholesterol :: Health, Dementia, Alzheimers Disease

Evidence is increasing concerning an association among vascular risk factors in midlife with an increased risk of both Alzheimer’s disease and vascular dementia decades later (citation). Diverse studies have found total cholesterol measured in midlife to be a significant predictor of subsequent dementia (Whitmer et al., 2005), mild cognitive impairment (Kalmijn et al., 2000) or cognitive decline (Kivipelto et al., 2001). Total cholesterol on midlife was also associated with Alzheimer’s disease (AD) in some studies (Kivipelto et al., 2001) and especially with concomitant hypertension (Beeri et al., 2009). Meanwhile, the exact mechanism of high blood cholesterol in dementia is not known, because cholesterol is not able to pass the blood-brain barrier (BBB) (Bojanic et al., 2010). Beyond that, observational studies have yielded mix results for lipids levels and cerebrovascular disease risk (Bowman et al., 2003). Of interest, lipid abnormalities have been also implicated in the pathogenesis of ischemic cerebrovascular disease (Demchuk et al., 1999; Goldstein, 2007). Stroke contributes to the development of cognitive disorders in nearly 20% of elderly patients (citation). Stroke related features such as multiple strokes, white matter lesions, left hemisphere infarct location, atrophy, and volume of infarcted tissue are associated with an increased risk of post-stroke dementia (Rasquin et al., 2004). Nevertheless, even though a decrease in cholesterol concentrations with statins can reduce the incidence of stroke in high-risk populations and in patients with a stroke or transient ischemic attack (Amarenco et al., 2006), serum cholesterol traditionally has been considered a poor predictor of total stroke risk (Ansell, 2000) and epidemiological evidence has failed to demonstrated a clear relationship between the risk of stroke and serum cholesterol levels (citation). Mild cognitive impairment (MCI) refers to the transitional state between the cognitive changes of normal aging and very early dementia (Petersen and Negash, 2008). MCI is defined as memory deficits with preservation of other cognitive and functional brain activities (Nestor et al., 2004). However, whether the MCI results from neuronal loss within circuit-specific pathways involved in learning and memory (Verkhratsky et al., 2004) and/or from cerebrovascular deregulation within these pathways (Iodecola et al., 2004) remain debatable. The aim of the current study was to determine whether a cognitive impairment associated with elevated plasma cholesterol levels over aging is related with structural pathology or white matter disease (vascular lesions?