Researchers have long understood that the mental and functional deterioration caused by Alzheimer's disease (AD) is related to the increasing presence of physical abnormalities in the brain, and particularly in those brain sectors controlling thought, memory and language.
Now research from Washington University in St. Louis has begun to link specific cognitive problems with specific brain abnormalities, thus paving the way for a better understanding of cause and effect in the onset and progression of Alzheimer's.
"This is one of the first studies that links specific patterns of cognitive decline with specific Alzheimer's pathology from distinct anatomic areas," said Stephen Kanne, primary investigator for the project and a doctoral student in psychology in Arts and Sciences at Washington University.
"It also confirms the power of neuropsychological tests to predict in fairly early stages of the disease where a particular patient is likely to have specific brain damage five years later, when the disease has progressed to a more severe form."
Published in the April 1998 issue of the journal Neurology, the study is based on an analysis of brain tissues obtained from 41 patients who died within about five years of receiving comprehensive neuropsychological assessments for signs of Alzheimer's related dementia. Subjects were drawn from a pool of 668 individuals with an average age of 75 whose cognitive abilities were tracked by the Washington University Alzheimer's Disease Research Center.
The research was funded by a grant from the National Institute on Aging and conducted by a interdisciplinary team of researchers from the psychology, neurology and pathology departments at Washington University. Other members of the research team are John C. Morris, M.D., a professor of neurology and pathology and director of the Memory and Aging Project; and Daniel W. McKeel Jr., M.D., an associate professor of pathology whose laboratory maintains a collection of more than 450 human brains used in research projects at the School of Medicine.
Subjects who showed no signs of Alzheimer's-related dementia during their clinical examinations were assessed as having only small declines in cognitive abilities, declines consistent with normal aging. However, subjects who showed early signs of Alzheimer's displayed significant patterns of cognitive impairment on these assessments. Five years later, significant patterns of abnormal brain damage emerged in autopsies of these subjects. Most important, the patterns of brain damage found in these Alzheimer's sufferers could be related in meaningful ways to specific cognitive problems documented during the assessments.
"The study documents the existence of cored senile plaques -- one of the markers for the diagnosis of Alzheimer's disease -- in areas of the brain supporting the very same cognitive skills for which subjects exhibited diminished function in tests conducted about five years earlier," said David Balota, Ph.D., research team member and professor of psychology. "The later autopsy confirmation that senile plaques exist in these brain areas does not necessarily confirm that the plaques caused the dysfunction, but the results are clearly consistent with this assumption."
The study documents, for instance, that subjects who performed relatively poorly (compared to their overall test performance) on tests of memory were later found to have relatively more Alzheimer's-related deterioration in the temporal lobe, a sector of the brain known to play an important role in the performance of these functions.
Similarly, subjects with early stage Alzheimer's who performed more relatively poorly on tests of visual and spatial skills were later found to have relatively more abnormalities in the parietal sector of the brain, and those who scored relatively poorly on tests of mental control, were found to have relatively more Alzheimer's damage to the frontal lobe -- findings that coincide with a general understanding of the role these brain sectors play in the cognitive process.
Challenge To Researchers
"One reason the research is important is that it suggests that Alzheimer's affects different regions of the brain in different people -- that means early symptoms of the disease won't be the same in everyone," said investigative team member Martha Storandt, Ph.D., a professor of psychology whose research explores differences between normal aging and Alzheimer's disease.
"The discovery is not good news for Alzheimer's researchers," Storandt said, "because it means that any theories we develop about what causes the disease must allow for this variability, and doing so presents more challenging scientific problems than we faced with other degenerative diseases, such as Parkinson's, in which the damage to the brain is more localized."