Autopsy study of mild cognitive impairment

May 9 2006

A study led by Mayo Clinic demonstrates that mild cognitive impairment, a memory disorder considered a strong early predictor of Alzheimer's disease, not only results in behavioral symptoms, but also structural changes that can be identified in the brain. Findings will be published in the May issue of Archives of Neurology.

"I think our study provides an anatomical basis for the clinical condition of mild cognitive impairment," says Joseph Parisi, M.D., Mayo Clinic neuropathologist and study investigator. "This shows that there are structural changes in the brains of patients who may develop Alzheimer's disease."

This study, funded by the National Institute on Aging, is one of the first autopsy studies of mild cognitive impairment.

"Our examination of the brains of those who died while they had mild cognitive impairment shows us that neuropathologically they are not normal, but they do not have the changes of fully developed Alzheimer's disease," says Ronald Petersen, M.D., Ph.D., Mayo Clinic neurologist and study investigator. "These early findings led us to believe that these people were on the road to developing Alzheimer's, but they weren't there yet. They have only a few of the features of Alzheimer's in their brains. Just like they clinically looked in between normal aging and Alzheimer's disease, their brains also looked in between. It is a confirmation of a transitional condition between normal and Alzheimer's disease."

The study's intent was to determine the features of the brains of those who died while in the clinical state of mild cognitive impairment, showing behavioral symptoms of the condition. Autopsies were performed by Mayo Clinic pathologists on the brains of 15 people who died while they had clinical mild cognitive impairment, as well as on the brains of 28 patients who were cognitively normal and 23 with probable Alzheimer's, a disease that ultimately can only be diagnosed after death. The researchers found that most of the brains of those who had been clinically diagnosed with mild cognitive impairment did not meet the pathological criteria for Alzheimer's disease, but rather showed changes suggesting progression toward Alzheimer's. All these brains possessed plaques and tangles -- hallmarks of Alzheimer's disease -- beyond what would be expected in normal aging, yet shy of full Alzheimer's. Plaques and tangles result from deposits of abnormal proteins in the brain, causing a slowly progressive loss of neurons.

"Mild cognitive impairment is by definition a disorder of cognitive function," says Dennis Dickson, M.D., Mayo Clinic neuropathologist and study investigator. "When we look at the brain, we can't see cognition, but we can see degenerative changes. In general, in the brains of those with mild cognitive impairment the plaques and tangles that are the hallmark of Alzheimer's disease were present, but in less severity and confined to a specific area, unlike Alzheimer's, in which plaques and tangles are widespread throughout the brain."

Dr. Dickson points out that density and spread of plaques and tangles are not sufficient alone to identify those who are normal or who have mild cognitive impairment or Alzheimer's. "Some people can compensate for the pathology in their brains," he explains. "They can have a high burden of plaques and tangles and yet be normal. This may be due to factors like education, activity or life experiences. If I sat down and grouped brains by normal, mild cognitive impairment and Alzheimer's, I'd be wrong in a number of cases. It doesn't map exactly that if you're normal you have no plaques and tangles, and if you have Alzheimer's you have a large amount of plaques and tangles. But generally, the more plaques and tangles you have in the brain, the more cognitively impaired you will be."

The plaques and tangles that are present in the majority of the brains of those with mild cognitive impairment will lead to a gradual breakdown of the very elaborate circuitry of the brain in which normal neurons stop functioning and memory is affected, says Dr. Parisi.

"Everything's wired in the brain," says Dr. Dickson. "When a neuron dies, it's as if that circuit is shorted out, which presents itself as cognitive impairment and eventually dementia."

The researchers say that people can contribute to research in Alzheimer's and its preconditions by having an autopsy performed on a loved one with such a condition.