BALTIMORE – The interaction of cerebrovascular disease and Alzheimer's disease pathology appears to significantly increase the risk of dementia, Dr. Richard O'Brien said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.
“Having cerebrovascular disease on top of just a little Alzheimer's pathology pushes you over the edge into being demented,” said Dr. O'Brien, reporting on data from the Baltimore Longitudinal Study of Aging (BLSA).
The BLSA was initiated in 1958 with the aim of helping researchers learn what happens as people age and sort out changes caused by aging from those caused by disease or other causes. Current enrollment is 2,135 volunteers, and 219 deceased participants are included in the autopsy component. Participants are evaluated yearly.
As of the last analysis in December 2006, 175 brains with normal, stroke, and/or Alzheimer's disease (AD) pathology had been autopsied. The average age at death was 87 years (range 57–102 years), and the group was predominantly male (69%). The group was generally well educated with an average of 18 years of schooling. Overall, 104 had a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) pathology score of 2 or greater, indicating AD pathology. A total of 77 had had at least one stroke.
In those with no stroke, AD pathology could be relatively severe (up to a CERAD score of 2) and still have a relatively low risk of dementia. However, when at least one stroke has occurred, the risk of dementia jumps substantially with only a small amount of AD pathology (CERAD 1). In the absence of AD pathology, it takes about three cortical strokes to induce dementia. When there is moderate AD pathology (CERAD 2), dementia is apparent after two strokes on average. It was possible for patients with moderate AD pathology to never progress to dementia, as long as they remained free of strokes, said Dr. O'Brien, a professor of neurology at Johns Hopkins University, Baltimore.
Stroke alone increased the risk of dementia in this cohort as well. Of those with evidence of stroke on autopsy, 37 had symptomatic strokes. These patients had a fourfold greater risk of dementia than did those with no evidence of stroke. The remaining 40 participants with evidence of stroke at autopsy were asymptomatic. These individuals also had an increased risk of dementia (odds ratio 3.2). “Having a stroke significantly increased your risk of being demented, whether or not that stroke was clinically symptomatic,” said Dr. O'Brien, who is also chair of neurology at Johns Hopkins Bayview Medical Center in Baltimore.
When it comes to the association between strokes and dementia risk, numbers and location matter. “The more strokes you have, the more likely you are to be demented.” The researchers found that only the strokes that occur in the cortex increase the risk of becoming demented,” Dr. O'Brien said. The chance of being demented with one stroke was about 50%, the chance with two strokes was about 80%, and the chance with three strokes was 100%. Strokes in the subcortical part of the brain were not significantly related to dementia.
Stroke size was not a factor in dementia risk. Large strokes tend to be symptomatic. However, in this group the presence of asymptomatic (and presumably small) strokes still conferred a greater risk of dementia. In addition, microstrokes–those occurring in the cortex and requiring a microscope to see–were as likely to increase the risk of becoming demented as a very large stroke in this cohort.
If an older person is cognitively normal before a stroke, the chance of becoming demented is the same as for the age-matched stroke-free population. However, for those who have some cognition problems prior to a stroke, the chance of becoming demented after a stroke is extraordinarily high–a 40-fold increased risk, he said. Dr. O'Brien disclosed that he has no potential conflicts of interest.
The left image shows plaques and tangles (CERAD 2). The right image shows a middle cerebral artery stroke on an autopsy specimen. Photos courtesy Dr. Richard O'Brien
