Hypertension and Hypercholesterolaemia as Risk Factors for Alzheimer??s Disease

Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland.
CNS Drugs (Impact Factor: 5.11). 02/2002; 16(7):435-44. DOI: 10.2165/00023210-200216070-00001
Source: PubMed


This paper focuses on hypertension and hypercholesterolaemia as risk factors for Alzheimer's disease and, as such, subjects for prevention. The long-term, prospective, population-based studies regarding the relationship between hypertension or hypercholesterolaemia and Alzheimer's disease, and the clinical studies regarding the association between antihypertensive or lipid-lowering medications and the risk of Alzheimer's disease, are reviewed. These studies provide evidence to suggest that elevated blood pressure and cholesterol levels earlier in life may have an important role in the development and expression of late-life Alzheimer's disease. Based on these data, we propose that proper, early interventions aimed at reducing these cardiovascular risk factors may have an impact on the future incidence and prevalence of Alzheimer's disease.

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    • "Many clinical and epidemiological studies support the role of metabolic disorders, such as midlife hypercholesterolemia or metabolic syndrome, as risk factors to suffer AD (Kivipelto et al., 2002; Pappolla et al., 2003; Muller et al., 2007; Razay et al., 2007). Type 2 diabetes (T2D) is the metabolic alteration that has been most widely assessed as an AD risk factor (Ott et al., 1996, 1999; Hassing et al., 2004; Luchsinger et al., 2007), leading to the description of a complex syndrome: type 3 diabetes (de la Monte et al., 2006). "
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    ABSTRACT: Age remains the main risk factor for developing Alzheimer's disease (AD) although certain metabolic alterations, including prediabetes and hyperinsulinemia, also increase this risk. We present a mouse model of AD (APPswe/PS1dE9 mouse) with severe hyperinsulinemia induced by long-term high fat diet (HFD) treatment. After 23 weeks on HFD learning and memory processes were compromised. We observed a significant increase in tau hyperphosphorylation and Aβ pathology, including Aβ levels and amyloid burden. Microglia activation was also significantly increased in HFD-treated mice, both in close proximity to and far from senile plaques. Insulin degrading enzyme and neprilysin levels were not affected, suggesting that Aβ degradation pathways were preserved, whereas we detected an increase in spontaneous cortical bleeding that could underlay an impairment of Aβ interstitial fluid drainage, contributing to the increase in Aβ deposition in APP/PS1-HFD mice. Altogether our data suggest that early hyperinsulinemia is enough to exacerbate AD pathology observed in APP/PS1 mice, and supports the role of insulin-resistance therapies to stop or delay central complications associated.
    Psychoneuroendocrinology 06/2014; 48C:123-135. DOI:10.1016/j.psyneuen.2014.06.005 · 4.94 Impact Factor
    • "The altered biosynthesis, turnover, APOE-dependent transport , and catabolism of cholesterol to oxysterols (e.g., 24S-hydroxycholesterol) in brain is thought to play a key role in AD pathogenesis which is evidenced by many experimental as well as postmortem neuropathological studies [46] [47] [48]. Some epidemiological studies have indicated that hypercholesterolemia is a risk factor for AD, and others have shown that an increased total cholesterol is associated with increased risk of AD as also with aggravated progression of the disease process in subjects who are APOE4 negative, but not in those carrying at least one allele of APOE4 [49] [50] [51] [52]. "
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    ABSTRACT: Cerebral hypometabolism of glucose, weight loss, and decreased food intake are characteristic features of sporadic Alzheimer's disease (AD). A systematic study on the serum levels of adipokines and insulin, the major hormones regulating energy metabolism, food intake, and body weight, in sporadic AD is necessary. The present study compares the serum levels of leptin, adiponectin, and insulin, measured by commercially available immuno-assay kits, between controls and sporadic AD subjects. The results show a conspicuous decrease in the level of leptin, a dramatic rise in the level of adiponectin, and also a statistically significant increase in insulin level, in the blood of AD subjects, with respect to controls. The changes in the serum levels of adiponectin and insulin in AD are positively correlated with the severity of dementia. Likewise, the serum level of leptin in AD subjects is negatively correlated with the degree of dementia. The changes in the levels of adipokines and insulin have implications in the amyloid pathology, neurodegeneration, and hypometabolism of glucose existing in the AD brain.
    Journal of Alzheimer's disease: JAD 03/2014; 41(2). DOI:10.3233/JAD-140006 · 4.15 Impact Factor
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    • "Arterial hypertension is among the most important and most frequent cardiovascular disorders, in particular in the developing world. Hypertension is normally silent, asymptomatic and preventable, but if remained uncontrolled, it could progress into severe cardiovascular (Davies, 1991), cerebrovascular (Ogunniyi & Talabi, 2001), peripheral vascular (Makin et al., 2001) and neurodegenerative complications (Kivipelto et al., 2002). Regulation of hypertension is the result of a delicate balance between cardiac output and peripheral vascular resistance (Vikrant & Tiwari, 2001). "
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    ABSTRACT: Abstract Context: Citrus spp. (Rutaceae) are well-documented for their cardioprotective properties. Auraptene is a bioactive monoterpene coumarin ether abundantly present in the Citrus spp. Objective: To investigate the hypotensive activity of auraptene. Methods: Different groups of normotensive rats (n = 5 in each group) were subjected to single intravenous injections of auraptene (125, 250 and 500 µg/kg), nifedipine (as positive control; 63, 125 and 250 µg/kg) or negative control [DMSO/normal saline (1:3)]. Mean arterial blood pressure (MABP) and heart rate (HR) were evaluated following each treatment. Results: A dose-dependent hypotensive effect was observed following auraptene injection, which was significant at 250 and 500 µg/kg (p < 0.001) but not 125 µg/kg (p > 0.05). With respect to the positive control, nifedipine reduced MABP at all tested doses, dose-dependently and significantly (p < 0.001). The MABP lowering effect of auraptene was found to be significantly lower than that of nifedipine (p < 0.001). Conclusion: In light of the present findings, auraptene has moderate hypotensive activity. Further investigations are recommended to explore the effects of higher doses as well as oral administration of this phytochemical.
    Pharmaceutical Biology 02/2013; 51(5). DOI:10.3109/13880209.2012.747546 · 1.24 Impact Factor
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