The link between mild cognitive impairment and Alzheimer's disease pathology grows stronger with a study in this month's Annals of Neurology. Kathy Riley, David Snowdon, and William Markesbery of the University of Kentucky report a strong correlation between degree of neurofibrillary pathology on autopsy and pre-death cognitive state in 135 participants of the ongoing Nun Study.

From the subjects with minimal neurofibrillary pathology to those with heavy and widespread tangle burden, the degree of tangles paralleled increasingly poor performance on cognitive tests taken within a few months before death. The data also indicate that subjects with memory impairments in addition to other cognitive deficits had more tangles than subjects with non-memory cognitive deficits alone, and were more likely to be diagnosed with Alzheimer's disease over a four-year period.—Hakon Heimer

Comment by Kathy Riley-Posted 24 March 2002
"In the Nun Study, a longitudinal study of aging and Alzheimer's disease in women aged 75-107, we have been interested in understanding the very earliest stages of cognitive impairment in older adults, as well as more severe impairment and dementia. In the present study of 130 participants, cognitive function ranged from fully intact to demented, and included mild cognitive impairments. Mild cognitive impairments in individuals who did not have dementia were associated with more severe Alzheimer's disease pathology, measured primarily by the Braak staging method, which focuses on neurofibrillary tangles. In addition, over half of the participants who had mild memory impairments had developed dementia (Alzheimer's disease) by their last cognitive exam before death. However, our findings underscore the fact that not all people who have mild cognitive impairments develop dementia during their lifetime.

Our data, as well as recent findings of other researchers, demonstrated that Alzheimer's disease neuropathology is an underlying factor in mild cognitive impairments. It is also likely that additional factors (infarcts, advanced age, cerebral atherosclerosis) may help explain additional variance in cognitive impairment beyond that which can be attributed to the severity of Alzheimer's pathology. For example, our data showed that degree of atrophy of the neocortex was significantly related to the presence of dementia in this sample of 130 participants. The identification of these factors will assist in predicting who will develop mild impairments and who is most likely to go on to develop the more severe symptoms of Alzheimer's disease. We are currently exploring the relationship between small strokes and mild cognitive impairments, and are examining the predictors of mild forms of cognitive impairment. We are investigating whether or not those same factors predict who will go on to develop the full symptoms of dementia. Data are still needed to more fully explain what may help protect against the clinical expression of dementia and what might hasten its appearance in persons who have relatively mild degrees of Alzheimer's pathology."—Kathryn Riley, University of Kentucky.


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Primary Papers

  1. . Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol. 2002 May;51(5):567-77. PubMed.