Public Release: 

Tests reveal subtle signs of Alzheimer's before clinical symptoms appear

University of California - San Diego

Researchers report that "paper-and-pencil" neuropsychological tests administered to normal subjects averaging 75 years of age contained early signs of cognitive decline in those subjects who later developed Alzheimer's disease.

In an analysis of cognitive performance test data from 40 participants enrolled in a long-term study at the UCSD Alzheimer's Disease Research Center (ADRC), a research team from the Veterans Affairs San Diego Healthcare System and the UCSD School of Medicine noted subtle evidence of changes that might signal the onset of cognitive decline. All participants were symptom-free when they took the test, with 20 of the subjects diagnosed with Alzheimer' disease (AD) within a year or two of testing. The other 20 have remained symptom-free for several years, serving as a matched control group.

When the team compared the data from the cognitive performance tests, they observed significantly greater discrepancies in the cognitive skills of the pre-AD group than in the control group, according to the study's lead author, Mark Jacobson, Ph.D., research psychologist with the VA Healthcare System and assistant project scientist with the UCSD department of psychiatry.

In particular, the results revealed early asymmetric decline, with the pre-AD subjects showing larger and more frequent discrepancies in their ability to perform visual versus verbal tests. These changes occur unevenly, affecting certain performance measures and not others, indicating subtle patterns of deterioration of specific regions of the brain affected by AD.

"We saw a larger discrepancy between the results of the non-verbal spatial tests and the verbal tests in the subjects who later were diagnosed with Alzheimer's disease," said Jacobson. "Since these changes are very subtle and not noticeable if you are only looking at one single area, our findings suggest that we should be comparing performance in different areas as they relate to one another to detect early changes in cognitive function."

For example, in these cognitive tests, subjects are asked to name common items from pictures, and to reconstruct drawings of block structures using actual building blocks. When the team went back and compared the results of these tests between the two groups, the pre-AD group had much greater performance gaps between their ability to name objects and their ability to reconstruct the block images. The control group had a much lower performance gap, with their ability to perform in both areas more even.

The team concludes that these non-invasive cognitive tests might be useful to detect early signs of AD in people who are otherwise symptom-free, providing one more way to identify those who might benefit from early treatment designed to slow the progression of AD. This might be especially useful in people with a strong family history or who are otherwise considered at high risk of developing the disease.

The study also provides new data about the course of cognitive changes associated with AD and how brain function is affected in the earliest stages of the disease. While the team is cautious about linking these cognitive changes to actual changes in the brain, they suggest that future functional magnetic resonance imaging studies might assist in identifying any neural basis for these cognitive changes.


This study was funded with support from the Veterans Administration, Veterans Medical Research Foundation, and the National Institute on Aging.

Co-authors are Dean C. Delis, Ph.D., of the VA San Diego Healthcare System and professor in residence, UCSD department of psychiatry; Mark W. Bondi, Ph.D., of the VA San Diego Healthcare System and assistant professor in residence, UCSD department of psychiatry, and David P. Salmon, Ph.D., professor in residence, UCSD department of neurosciences and the UCSD Alzheimer's Research Center.

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