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Mixed pathologies likely cause dementia in the oldest-old

The brains of people who live to age 90 and older—the oldest-old—usually have a mix of pathologies associated with dementia. Alzheimer’s disease-related brain changes are the most common, but other pathologies often found at autopsy include infarcts, Lewy bodies, hippocampal sclerosis, and white-matter disease. For the first time, researchers examined the relationship between the number of pathologies found at autopsy and the severity of dementia in the oldest-old. They found the more pathologies present in the brain, the more severe the dementia, and that Alzheimer’s pathology alone was less damaging to cognition than mixed pathologies.

The study led by Claudia Kawas, M.D., and Maria M. Corrada, Sc.D., University of California, Irvine, involved 183 volunteers in The 90+ Study, one of the largest studies tracking the well-being of the oldest-old in the world. The participants, 70 percent of whom were women, received physical and cognitive testing every 6 months. When they died at an average age of 97, about 54 percent were diagnosed with dementia. Their donated brains were examined for eight different cerebral pathologies.

The investigators found:

  • Alzheimer’s pathology alone was less likely to result in dementia. Alzheimer’s was found in about the same number of people with dementia (28 percent) and those without symptoms (23 percent).
  • Mixed pathologies, however, increased risk for dementia; they were found in 45 percent of those with dementia and in 14 percent of symptom-free volunteers.
  • Non-Alzheimer’s disease pathologies appeared more likely to result in dementia. People with a single non-Alzheimer’s pathology were 12 times more likely to have dementia than those with no pathology. In contrast, those with Alzheimer’s pathology were 3 times more likely to have dementia than those with no pathology.
  • Dementia prevalence increased with the number of pathologies found in the brain, from 22 percent in people with no pathologies to 95 percent of those with 3 or more pathologies.
  • Dementia severity also increased in direct proportion to the number of pathologies found in the brain. For example, people with mixed pathologies, such as Alzheimer’s hippocampal sclerosis and white-matter disease, had more severe symptoms than those who only had Alzheimer’s pathology.

Reference: Kawas, C.H., et al. Multiple pathologies are common and related to dementia in the oldest-old: the 90+ Study. Neurology. Epub 2015 Jul 15, 2015.