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Cardiovascular risk factors

Prevention of dementia

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Recent epidemiological evidence suggests an association between AD and vascular risk factors such as arterial hypertension, diabetes mellitus, general atherosclerosis and arterial fibrillation. Control of vascular risk factors could prevent the development of dementia. Future dementia can be significantly predicted by high age (?47 years), low education (<10 years), hypertension, hypercholesterinemia and obesity.

There is an association of type 2 diabetes mellitus, hypertension, dyslipidaemia and obesity with dementia. Risk of dementia was generally largest in studies that measured these risk factors at midlife (compared to late life) and had a long follow-up time. At midlife, the population attributable risk of dementia among these cardiovascular risk factors was highest for hypertension. Later in life diabetes appears to convey the highest risk of dementia.

Hypertension

Hypertension has received a lot of attention because it may represent a common and potentially modifiable risk factor not only for cardiovascular and cerebrovascular disorders but also for AD. Long-term population-based follow-up studies have shown that high blood pressure (BP), especially at midlife, is associated with an increased AD risk later in life. Whether low BP accelerates the AD process after onset of the illness is still a matter of debate. Longstanding hypertension may lead to various changes in cerebral arteries and alters the autoregulation of blood flow to the brain. Under these conditions, episodes of hypotension may lead to hypoperfusion and ischemia in vulnerable brain areas. These brain changes may further impair cognition. Some observational studies indicated that antihypertensive medication, especially long-term treatment, may reduce the risk of dementia, including AD. As results are contradictory, more information especially about possible effects of treatment of hypertension at midlife is needed.

Cholesterol

High serum total cholesterol (TC) values at midlife increases the risk of late-life AD. Midlife TC has also been related to AD-type brain changes in autopsy studies. The role of high cholesterol later in life and closer to dementia onset is less clear, as some studies indicate either no association or an inverse association of hypercholesterolemia with subsequent AD development. Recent data suggest a bidirectional relationship between TC and dementia; high TC is a risk factor for subsequent AD 20 years later, but decreasing TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life dementia. Little information is currently available regarding other cholesterol types (LDL, HDL, triglycerides). The brain is the most cholesterol rich organ in the body, and disturbances in brain cholesterol metabolism have been linked with all the main neuropathological changes in AD. Some experimental studies have shown that statins may reduce b-amyloid production in vitro and in vivo. The currently available epidemiological and clinical data on statins and AD give a rather mixed picture

Diabetes mellitus and metabolic syndrome

Diabetes has been associated with an increased risk of AD in several cohort studies, while others have found no association. In elderly, the true prevalence of diabetes mellitus (DM) is over 30%, and more than half of them are asymptomatic and undiagnosed. In addition, more than 30% have impaired glucose tolerance, which makes more than half of elderly people affected with hyperglycemia. The potential biological mechanisms underlying the diabetes-AD association are many. Diabetes is associated with changes in cerebral microvessels and BBB. Some studies have indicated that higher insulin levels are associated with the risk of dementia/AD. Besides indicators of diabetes and metabolic syndrome, inflammatory markers e.g. high CRP levels have also been suggested as risk factors for cognitive decline and AD. There seems to be an association between HbA1C level, which is a marker of glucose control) and risk of developing mild cognitive impairment (MCI) or dementia in postmenopausal osteoporotic women primarily without diabetes. These findings support the hypothesis that glucose dysregulation is a predictor for cognitive impairment.

Overweight and Obesity

The National Institutes of Health (NIH) define overweight in terms of the body mass index (BMI). The BMI is a person’s weight in kilograms (kg) divided by their height in metres (m) squared. Overweight is a BMI of 27.3% or more for women and 27.8% or more for men, while obesity is defined as a BMI of 30 and above, according to the NIH. The prevalence of overweight and obesity is more than 50% among adults in Europe and the United States. Obesity is increasing across the world, with severe consequences on cardiovascular health, but its association with the risk of AD has so far been less extensively studied. Weight loss seems to occur during the pre-clinical phases of dementia, and recent follow-up studies have suggested that low body mass index (BMI) could actually be an early sign of dementia. There is increasing evidence from long-term population-based studies that high BMI at midlife, or at late-life 9-18 years prior to dementia is associated with an increased AD risk. The prevention of overweight and obesity, even at greater ages, might be important for the prevention of dementia. Only a few studies have investigated the association between fat intake and the risk of dementia. It has been reported that high saturated fat and cholesterol intakes might be risk factors for Alzheimer disease, particularly among individuals carrying the apolipoprotein E e4 allele. Several studies have shown an association between higher intake of total calories and fats in elderly individuals without dementia and higher risk of Alzheimer’s disease, particularly in carriers of the APOE e4 allele. Central obesity in midlife increases the risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled. There seems to be a J-shaped relationship between BMI and dementia, such as being overweight and being underweight increase the risk of dementia in late life.

In a Finnish study on obesity at midlife (BMI 30kg/m²) was associated with the risk of dementia and AD even after adjusting for possible confounding factors like sociodemographic status. Midlife obesity, high total cholesterol level, and high systolic blood pressure were all significant risk factors for dementia.

Obesity at midlife is associated with an increased risk of dementia and AD later in life. The role of weight reduction for the prevention of dementia needs to be further investigated.

 

 
 

Last Updated: jeudi 08 octobre 2009

 

 
  • Acknowledgements

    The EuroCoDe project received financial support from the European Commission. Neither the European Commission nor any person acting on its behalf is responsible for any use that might be made of the following information. Alzheimer Europe also gratefully acknowledges the support it received from Fondation Médéric Alzheimer for this project.
  • European Union
  • Fondation Médéric Alzheimer
 
 

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