As we’ve seen with exercise and diet, evidence suggests that what may be good for the heart may be good for the brain. Moreover, metabolic changes that occur in a variety of chronic diseases of aging, such as heart disease, stroke, high blood pressure, and diabetes, may contribute to the development of AD, affect the severity of AD, or cause vascular dementia (Luchsinger et al., 2005; Curb, 2005).
However, it has been difficult to untangle the association between AD and these chronic diseases. Scientists have offered several possible explanations. For example, many believe that atherosclerosis, which may or may not be clinically apparent as heart disease or stroke, may add to or accelerate cognitive decline in people who already have AD. Or, it is possible that metabolic changes related to chronic disease, such as elevated insulin levels in diabetes, may actually increase the amount of AD pathology that accumulates in brain tissue and directly contribute to the development of AD. Other possibilities or a combination of factors also may explain the associations. As we develop new strategies to treat AD, it will be important to know whether the metabolic changes related to chronic vascular disease actually increase the amount of AD pathology or whether they independently cause dementia.
These relationships need to be sorted out because heart disease and stroke are major causes of illness and death. Diabetes, high blood pressure, and other risk factors for these chronic diseases can, to a large extent, be modified by diet, exercise, and other lifestyle changes, so it is important to know whether reducing risks of or controlling diabetes and high blood pressure also may reduce AD risk.
Currently, much of our knowledge about the associations between heart disease, stroke, cognitive decline, and dementia comes from epidemiologic studies. For example, the NHLBI’s Cardiovascular Health Study and NIA’s Cardiovascular Health Cognition Study have provided valuable data about the relationships between cardiovascular risk factors and AD because they include cognitive decline and dementia related to vascular disease as a key element of their design. In two recent analyses of CHS data, University of Pittsburgh investigators explored the relationships between cardiovascular disease and dementia. In the first study, the investigators showed that the risk of AD was 30 percent higher in people who had a history of cardiovascular disease other than stroke, compared with those without such a history (Newman et al., 2005). In the second study, investigators showed that vascular dementia and mixed dementia (vascular dementia and AD occurring simultaneously) account for a large proportion of new dementia cases (Kuller et al., 2005). An important result of the study was that it demonstrated the value of MRI as a diagnostic tool (see "Major AD Research Initiatives" for more on NIA’s Neuroimaging Initiative).
Investigators working with HAAS data explored whether men with beta-amyloid plaques and NFTs had an increased chance of crossing the threshold to clinical dementia if they also had cerebrovascular damage (Petrovitch et al., 2005). These Pacific Health Research Institute investigators found that, indeed, in men who had NFTs, dementia increased with increasing plaque density, particularly in the presence of cerebrovascular damage. This association was strongest in men who had the fewest plaques, suggesting that preventing cerebrovascular damage may be critically important in preserving cognitive abilities in older people.
As this area of research has blossomed, investigators have conducted studies of additional groups to explore associations between vascular disease and AD. For example, researchers from the Rush University Alzheimer’s Disease Center have included cerebrovascular disease measures when examining brain tissue samples from deceased participants of the Religious Orders Study, a long-term study of aging among members of 40 religious communities (Bennett et al., 2005). Consistent with other studies, participants who had amnestic MCI had evidence of intermediate levels of both AD and stroke damage in their brain tissue. They also had clinical symptoms that were in between those of people without cognitive impairment and those of people with dementia.
Findings from these and other studies have provided sufficient evidence for NIA to support several clinical trials to investigate the association between heart disease risk and AD:
The possible association of diabetes, insulin processing, and AD also is generating much interest among AD investigators. Type II diabetes mellitus is a major public health problem in the U.S. because it affects about one in five Americans older than 65 and has many serious health complications. A number of epidemiologic studies have suggested that people with diabetes have an increased risk of late-life cognitive problems, including MCI and AD, either as a direct result of high levels of blood sugar (hyperglycemia) or because of the conditions that are often associated with diabetes, namely high blood pressure, abnormal blood cholesterol levels, or too much insulin in the blood (Launer, 2005). Laboratory studies also have identified several pathways through which hyperglycemia can reduce neuronal viability (Launer, 2005). These include increases in oxidative stress, damage to endothelial and vascular function, and changes in gene transcription and expression in neurons.
This evidence has spurred research on a variety of fronts, from epidemiologic studies, to test tube and animal studies, to clinical trials. The objective of these studies is to determine whether diabetes is a risk factor for cognitive decline, and if so, whether treatment for diabetes may help lower risk of cognitive decline or AD. NIA is currently funding several diabetes clinical trials to see whether treating one or other aspect of diabetes will affect cognitive health and AD progression:
<< Back | Next >>