Brain changes linked with Alzheimer’s years before symptoms appear

Brain changes linked with Alzheimer’s years before symptoms appear

Press releases may be edited for formatting or style | May 15, 2019 Alzheimers/Neurology MRI

In the 81 people who developed cognitive problems or dementia, the Johns Hopkins team found subtle changes in cognitive test scores 11 to 15 years before the onset of clear cognitive impairment. They also found increases in the rate of change of a protein called Tau, which has long been considered a marker of Alzheimer’s disease, in cerebrospinal fluid an average of 34.4 years (for t-tau, or total Tau) and 13 years (for a modified version called p-tau) before the beginning of cognitive impairment.

In addition, the scientists detected slight decreases in the rate of change of the size of the medial temporal lobe, an area of the brain responsible for memory, between three and nine years before cognitive impairment was apparent.


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To find common patterns among the huge variations in brain anatomy among the MRI images of the study participants, Johns Hopkins biomedical engineering director Michael I. Miller, Ph.D., and the team used computer-based algorithms to assign numbers to brain anatomy. They then tracked the study participants’ brain anatomies over time to find changes in the numeric patterns consistent with cognitive impairment.

In another study described online in December 2018, Miller’s team used the same computational methods from the current study to find that people who have mild cognitive impairment have tissue shrinkage in an area within the medial temporal lobe of the brain, called the transentorhinal cortex.

“Several biochemical and anatomic measures can be seen changing up to a decade or more before the onset of clinical symptoms,” says Miller, the Bessie Darling Massey Professor and Director of the Department of Biomedical Engineering at The Johns Hopkins University. “The goal is to find the right combination of markers that indicate increased risk for cognitive impairment, and to use that tool to guide eventual interventions to help stave it off.”

More than 5 million people in the U.S. above age 65 have Alzheimer’s disease, the most common cause of dementia among this population. It is marked by progressive worsening of memory and thinking skills. The BIOCARD project, funded by the National Institutes of Health’s National Institute on Aging, is managed by the Johns Hopkins Alzheimer’s Disease Research Center.

Other scientists who conducted the research include Abhay Moghekar, Anja Soldan and Corinne Pettigrew from Johns Hopkins.

The study was funded by grants from the National Institutes of Health (U19-AG03365 and P50-AG005146).

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