TORONTO—The risk factors for stroke, such as high blood pressure, high cholesterol levels, and obesity, can also be used to determine a person’s risk of cognitive decline and dementia, according to research from the Framingham Heart Study, which was presented at the 62nd Annual Meeting of the American Academy of Neurology. Identifying an individual’s midlife stroke risk profile may help to prevent or delay the onset of Alzheimer’s disease and dementia through preventive interventions, reported Philip A. Wolf, MD, principal investigator of the study and Professor of Neurology at Boston University School of Medicine.
The lifetime risk of dementia is one in five for women and one in seven in men, and the lifetime risk of dementia or stroke is one in two for women and one in three for men. “If it were possible to delay the onset of dementia by five years, one would reduce the incidence of dementia for men or women by about half,” Dr. Wolf said.
The Framingham Heart Study, which is currently evaluating its third generation of subjects, began in 1948 with a cohort of 5,209 men and women from Framingham, Massachusetts. Slightly more than 10% of the first-generation cohort (n = 580) developed dementia in their lifetime. Of those, about 80% were diagnosed with Alzheimer’s disease. The second generation, which was added in 1972, included approximately 5,000 children of the original cohort, and the third generation comprises about 4,100 grandchildren.
“With this third generation—we know about their grandparents and parents, the risk factors that were measured in all three generations, the presence of subclinical disease in the preceding generation, and something about their genes and other measures of the environment—we hope to put together a risk profile for clinical identification of persons at high risk of Alzheimer’s disease and dementia,” Dr. Wolf reported. “It is likely that the earlier one can intercede, the greater the impact [one will have] on preventing the cognitive deficits that precede clinical dementia.”
Cognitive Screening
In the six decades since the study began, researchers have identified several risk factors for heart disease and stroke, including high cholesterol levels, high blood pressure, diabetes, and obesity. In the 1970s, a cognitive screening battery was added.
Using neuropsychologic exams and MRI scans in the second study generation, investigators were able to identify possible precursors to dementia and genetic risk factors. Data from the third generation are expected to help refine a risk profile for cognitive decline that may yield improved accuracy of prediction years before the appearance of clinical disease.
The researchers found that brain volume correlates with cognitive test scores and stroke risk. Subjects with the lowest stroke risk profiles compared to those with highest stroke risk profiles had a brain volume that was 2% greater. This difference in brain volume translates to a change that is equivalent to 10 years of aging.
Parental dementia is another strong risk factor for dementia, with an estimated 15-year impact on brain aging. Change in MRI and cognitive testing scores during the six-year period between ages 62 and 67 was greatest in those whose parents were diagnosed by Framingham Heart Study neurologists as having clinical dementia. These subjects also were more likely to have worsening performance in executive function and a higher degree of global brain atrophy, with a fourfold increase in atrophy in children of parents with Alzheimer’s disease.
Stroke, Dementia, and Alzheimer’s Disease
Dr. Wolf noted that there are believed to be two major pathways for dementia, the Alzheimer-related route and the vascular pathway. Stroke doubles a person’s risk of dementia, particularly vascular dementia, he said.
“Certainly a study designed to study vascular disease, such as Framingham, has collected a wealth of risk factor data dealing with the vascular pathology and details of subclinical vascular disease such as silent cerebral infarcts and cerebral micro bleeds. Documented [transient ischemic attacks] (TIAs), mild cognitive impairment (MCI), and ultimately stroke all play into this outcome of clinical disease,” he explained.
Midlife blood pressure is strongly correlated with both stroke and dementia. One study reported that the lifetime stroke risk ranged from 8% for those with normal blood pressure at midlife to three times that in those with stage II hypertension, Dr. Wolf noted.
Framingham researchers found that subjects who had higher blood pressure in their 40s were more likely to perform poorly on logical memory tests 20 years later. A midlife blood pressure increase of 40 mm Hg had an effect on logical memory performance equivalent to 10 years of aging. Individuals who performed poorly on logical memory tests had a 1.5 times increased risk of developing Alzheimer’s disease in the next 10 or 20 years.