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Two new articles address the role of vascular disease in producing or aggravating dementia in the elderly.
For 10 years, Gamaldo and colleagues followed 335 elderly subjects from the Baltimore Longitudinal Study of Aging. At study entry, all participants were about 75 years old, cognitively intact, and had not had a clinical stroke. A life-table (Kaplan-Meier) analysis indicated that, by age 90, 40% of survivors would be demented and 15% would have had a stroke. The 36 subjects who actually had a nonfatal clinical stroke during the study were more likely than those without a stroke to become demented during follow-up (odds ratio, 4.3). The increased risk for dementia, however, was significant only among subjects with mild cognitive impairment (MCI) prior to the stroke; cognitively normal participants with stroke during the study were no more likely to become demented than were participants without stroke. Absent stroke, vascular risk factors (hypertension, diabetes, elevated cholesterol, and coronary artery disease) did not increase the likelihood of dementia.
Regan and colleagues studied 224 patients with Alzheimer disease (AD), to determine whether vascular risk factors accelerate the progression of dementia. Over an 18-month period, decline in cognitive performance, behavioral symptoms, and impairment in activities of daily living were not related to any baseline vascular risk factors. Among the seven patients who had a stroke during follow-up, however, cognitive and functional ability declined significantly and behavioral scores decreased modestly, compared with participants without a stroke.
The authors of both studies conclude that when stroke is superimposed on underlying MCI or AD, the result is an accelerated loss of cognitive function.
Gamaldo A et al. Effect of a clinical stroke on the risk of dementia in a prospective cohort. Neurology 2006 Oct 24; 67:1363-9.
Regan C et al. Relationship of vascular risk to the progression of Alzheimer disease. Neurology 2006 Oct 24; 67:1357-62.
Comment
These findings raise two important questions: What happens to cognitive function when stroke is added to AD or MCI? And do risk factors for vascular disease either cause or accelerate the decline of AD?
Tissue loss from any cause has the potential to impair mental function, as Lashley recognized more than 75 years ago (Lashley KS. Brain mechanisms and intelligence: A quantitative study of injuries to the brain. University of Chicago Press; 1929). Tomlinson and Henderson noted that all patients with >100 cc infarct volume at autopsy had been demented during life. They termed the combination of AD and stroke “the multifactorial hypothesis of the etiology of dementia in old age” (Terry R and Gershon S, eds., Aging. Raven Press; 1976: 183). Once an aging brain has lost its reserve and crossed the threshold to dementia, further loss of brain due to stroke exaggerates the deficits.
Neither of the current studies supports the role of vascular factors in the etiology or acceleration of AD, but both were relatively small. Larger epidemiologic studies with many thousands of elderly subjects, such as the Framingham (N Engl J Med 2002; 346:476), Mayo Clinic (Am J Epidemiol 1997; 145:301), and Rotterdam (Neurobiol Aging 2000; 21:153) studies, have identified hypertension, diabetes, hypercholesterolemia, hyperhomocysteinemia, heart disease, atrial fibrillation, and atherosclerosis as likely risk factors for dementia and AD. Whether vascular disease can cause AD itself, or only exaggerates the cognitive deficits caused by brain tissue loss from AD, remains to be fully established.