Journal of Alzheimer's Disease - Volume 20, issue 3

Authors: Luzzi, Simona | Vella, Lucia | Bartolini, Marco | Provinciali, Leandro | Silvestrini, Mauro

Article Type: Review Article

Abstract: The relationship between cerebrovascular impairment and Alzheimer's disease is a controversial debate. An important and topical aspect in clinical research is the attempt to define the role of atherosclerosis and its determinants in the presentation and evolution of dementia. In this article, we discuss the evidence of the interaction between degenerative and vascular mechanisms in the pathogenesis of dementia. Moreover, we present data about the influence of hypertension and dyslipidemia, usually considered among the most important risk factors for atherosclerosis, on the evolution of Alzheimer's disease. The effects of antihypertensive and lipid-lowering drugs on cognitive impairment will be also discussed.

Keywords: Alzheimer's disease, atherosclerosis, cerebrovascular disease, dyslipidemia, hypertension

DOI: 10.3233/JAD-2010-091378

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 893-901, 2010

Authors: Duron, Emmanuelle | Hanon, Olivier

Article Type: Review Article

Abstract: Chronic hypertension is associated with an increased risk of both vascular dementia and Alzheimer's disease (AD). In this context, the role of anti-hypertensive therapy for the prevention and delay of cognitive decline and dementia is of central importance. Most longitudinal studies have shown a significant inverse association between anti-hypertensive therapies and dementia incidence and for some of these, particularly in AD. Seven randomized, double blind placebo-controlled trials have evaluated the benefit of antihypertensive treatments on cognition. Three of them found positive results in term of prevention of dementia (SYST-EUR) or cognitive decline (PROGRESS, HOPE). Others disclosed non-significant results (MRC, SHEP, …SCOPE, HYVET-COG). This discrepancy emphasizes the difficulty to perform such trials: the follow-up has to be long enough to disclose a benefit, a large number of patients is needed for these studies, and because of ethical reasons some anti-hypertensive treatments are often prescribed in the placebo group. Results of the two more recent meta-analyses are inconsistent, possibly due to methodological issues. Antihypertensive treatments could be beneficial to cognitive function by lowering blood pressure and/or by specific neuroprotective effect. Three main antihypertensive subclasses have been associated with a beneficial effect on cognitive function beyond blood pressure reduction (calcium channel blockers, angiotensin converting enzyme inhibitor, angiotensin-AT1-receptor-blockers). Further long-term randomized trials, designed especially to assess a link between antihypertensive therapy and cognitive decline or dementia are therefore needed with cognition as the primary outcome. A low blood pressure threshold that could be deleterious for cognitive function should also be determined. Show more

Keywords: Alzheimer's disease, a ntihypertensive therapy, cognitive decline, hypertension, longitudinal studies, meta-analyses, randomized controlled trials

DOI: 10.3233/JAD-2010-091552

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 903-914, 2010

Authors: Middleton, Laura E. | Yaffe, Kristine

Article Type: Review Article

Abstract: The prevalence of dementia is expected to increase dramatically over the upcoming decades due to the aging population. Since treatment is still short of a cure, preventative strategies are of the utmost importance. Stimulating activity (cognitive, physical, and social), vascular risk factors, and diet may be important in preventative strategies. Dementia risk may be modified by participation in stimulating activities. One study suggested that the cognitive, physical, and social components of activity were of equal importance to cognitive outcomes. However, while exercise interventions appear to benefit global cognition, the benefits from cognitive training appear to be domain specific. People with …vascular risk factors (hypertension, diabetes, dyslipidemia, and obesity) appear to be at higher risk for dementia than those without in observational and clinical trials. Controlled trials suggest that vascular risk management via some pharmaceutical interventions may benefit cognition, though results are inconsistent. Finally, people who adhere to a Mediterranean diet or who have high intake of antioxidants and omega-3 fatty acids have reduced likelihood of dementia in observational studies. However, supplementation in controlled trials has not generally proved successful at improving cognitive outcomes. A single supplement may be insufficient to prevent dementia; it may be that the overall diet is more important. Future large randomized controlled studies should examine whether interventions can reduce the risk of dementia and whether combining cognitive, physical, and social activity, vascular risk reduction, and dietary interventions might have additive or multiplicative effects. Show more

Keywords: Cognitive activity, dementia, diet, physical activity, prevention, social engagement, vascular risk

DOI: 10.3233/JAD-2010-091657

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 915-924, 2010

Authors: McGuinness, Bernadette | Passmore, Peter

Article Type: Review Article

Abstract: Evidence accumulating from biological and epidemiological studies suggests that high levels of serum cholesterol may promote the pathological processes that lead to Alzheimer's disease (AD). Lowering cholesterol in experimental animal models slows the expression of Alzheimer's pathology. These findings raise the possibility that treating humans with cholesterol lowering medications might reduce the risk of developing AD or help treat it. The statins (lovastatin, pravastatin, simvastatin, and others) are powerful cholesterol lowering agents of proven benefit in vascular disease. Several clinical studies comparing the occurrence of AD between users and non-users of statins suggested that risk of AD was substantially reduced …among the users. However, because these studies were not randomized trials, they provided insufficient evidence to recommend statin therapy. Cochrane reviews are based on the best available information about healthcare interventions and they focus primarily on randomized controlled trials (RCTs). On the issue of prevention, two randomized trials have been carried out and neither showed any reduction in occurrence of AD in patients treated with statins compared to those given placebo. Statins cannot therefore be recommended for the prevention of AD. Regarding treatment of AD, the large RCTs which have assessed this outcome have not published their results. Initial analysis from the studies available indicate statins have no benefit on the outcome measure ADAS-Cog but have a significant beneficial effect on MMSE as an outcome. We need to await full results from the RCTs before we can be certain. In addition statins were not detrimental to cognition in either systematic review. Show more

Keywords: Alzheimer's disease, cholesterol, cognitive impairment, dementia, statins

DOI: 10.3233/JAD-2010-091570

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 925-933, 2010

Authors: Murad, M. Hassan | Montori, Victor M.

Article Type: Review Article

Abstract: The two fundamental principles of evidence-based medicine indicate that a hierarchy of evidence exists and that evidence alone is never sufficient to make clinical decisions. Incorporation of factors other than evidence such as patients' values and preferences, clinical context, and resource allocation are essential factors for decision making. The knowledge of these principles orients the use of clinical care research by evidence users such as patients, clinicians, and policy makers; and also helps researchers create research protocols and agendas that produce evidence that fulfills the needs of these users. Examples of research in Alzheimer's disease are presented to illustrate how …evidence is produced, appraised and utilized. Show more

Keywords: Alzheimer's disease, evidence-based medicine, patients' values and preferences, quality of evidence, research methodology

DOI: 10.3233/JAD-2010-1419

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 935-942, 2010

Authors: Strobel, Gabrielle

Article Type: Editorial

DOI: 10.3233/JAD-2010-100013

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 943-948, 2010

Article Type: Announcement

DOI: 10.3233/JAD-2010-100082

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 949-951, 2010