"The study shows that mild cognitive impairment is often the earliest clinical manifestation of one or both of two common age-related neurologic diseases," said Dr. David A. Bennett, director of the Rush Alzheimer's Disease Center at Rush University Medical Center and the principal author of the paper. "From a clinical standpoint, even mild loss of cognitive function in older people should not be viewed as normal, but as an indication of a disease process," said Bennett.
This is the first study involving a large number of subjects who were followed until they developed mild cognitive impairment or dementia, and then died.. The study involved examining brain tissue from 180 people, including 37 with mild cognitive impairment, 60 without cognitive impairment, and the rest with dementia. All were Catholic nuns, priest or brothers who agreed to participate in the National Institute on Aging (NIA) funded Religious Orders Study. Since 1993 more than 1000 persons have agreed to annual clinical evaluations and to donate their brains to the Rush investigators at the time of death.
Study participants took tests of memory, language, attention and other cognitive abilities each year to document their clinical status. The diagnosis of mild cognitive impairment (MCI) was made when impaired performance on these tests was not severe enough to warrant a diagnosis of dementia. After death, the investigators measured the amount of Alzheimer's disease pathology and cerebral infarcts (strokes) through brain autopsy. Of the 37 individuals with MCI, more than half (23) met pathologic criteria for Alzheimer's disease, and nearly a third (12) had cerebral infarcts (this include five with both). Less than a quarter (9) did not have either pathology.
"Because most people with mild cognitive impairment progress to dementia, it has been difficult to obtain brain tissue from persons who die while they still have the condition," said Bennett. "We now know that both clinically and pathologically, mild cognitive impairment patients are in the middle in terms of the disease process for Alzheimer's disease and cerebral vascular disease," said Bennett.
One positive finding from the study is that one-third (60) of the total study participants with an average age of 85 did not experience cognitive decline over several years of follow-up. Yet, about half of these persons had significant Alzheimer's disease pathology and nearly a quarter had cerebral vascular disease. "It is likely that these individuals have some type of 'reserve' capacity in their brains that allows them to escape the loss of memory despite the accumulation of pathology," said Bennett.
Bennett and his colleagues are involved in another NIA funded study at Rush, the Memory and Aging Project, trying to identify what keeps these individuals from becoming impaired. "Preventing the accumulation of disease pathology is a common approach to disease prevention," said Bennett. "Another way to prevent loss of cognition is to identify factors that protect us from becoming forgetful despite this pathology.
"From a public health perspective, the number of people with cognitive loss due to Alzheimer's disease and cerebral vascular disease is probably much larger than current estimates," said Bennett. He hopes that these data provide additional impetus to research efforts to develop treatments and, ultimately, prevention for these common diseases of aging.
The study is funded by the National Institute on Aging.