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Studies Show that AD Brain Changes Occur Before Clinical Diagnosis

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By 1999 Progress Report by the NIA/NIH • • December 13, 1999

Several recent studies funded by NIA have attempted to explore the cause and development of Alzheimer's through examinations of the brains of individuals who have died, both those with Alzheimer's and those without. These studies allow researchers to track the changes in the brain that occur as Alzheimer's develops and to understand the damage that happens early, before clinical signs of AD appear. For example, scientists at the Washington University School of Medicine in St. Louis studied the distribution and density of tangles and plaques in 62 clinically followed cases, some of whom had mild dementia, some of whom had severe dementia at death, and some of whom were healthy at death (Price and Morris, 1999). They found that some of the healthy brains had either amyloid plaques or neurofibrillary tangles, suggesting that initial formation of tangles and plaques in healthy aging may be independent of each other. However, some of the brains of those who had been diagnosed with mild dementia had widely distributed plaques and a substantial increase in the number of tangles relative to the healthy brains. The study authors suggest that amyloid deposition somehow increases the rate at which tangles are formed as "preclinical" Alzheimer's disease progresses into clinically diagnosed dementia.

In another study looking at changes in neurofibrillary tangles in the brains of deceased elderly men and women who, during their lives, had no dementia, questionable dementia, mild dementia, and moderate dementia, a team of investigators at the Mount Sinai School of Medicine and Bronx Veterans Affairs Medical Center found that tangles were present in the entorhinal cortex and hippocampus of all the subjects (Haroutunian et al., 1999). As dementia became more severe however, the tangles appeared in additional regions of the brain and became more dense. These studies reinforce the idea that changes characteristic of those seen in the AD brain can begin in individuals well before any clinical diagnosis is made.

National Institutes of Health
National Institute on Aging

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