New Study Shows Lower Cerebral Blood Flow Precedes Brain Tissue Loss in Early Phase of Alzheimer’s Disease

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In their study “Early Amnestic Mild Cognitive Impairment is Associated with Reduced Total Cerebral Blood Flow with No Brain Tissue Loss,” published in the January issue of the Journal of Alzheimer’s Disease, researchers at the University of Miami Miller School of Medicine answered the pending question of whether reduced cerebral blood flow (CBF) precedes or follows brain tissue loss.

Man in lab coat standing outdoors
Noam Alperin, Ph.D.

Noam Alperin, Ph.D., professor in the Department of Radiology, and David Lowenstein, Ph.D. professor in the Department of Psychiatry and Behavioral Sciences, led the study along with co-first author Che Liu, a graduate student in the UM College of Engineering.

“Our objective was to assess the predictive value of cerebral blood flow and volumes of specific brain structures for identification of early phase of Alzheimer’s disease,” Dr. Alperin said. “To meet our objective, we assessed both CBF and volumes of memory-critical brain regions in normal and pre-clinical phase of AD.”

A total of 74 participants in their late 60s were classified into two groups, with 50 participants being cognitively normal and 24 with early amnestic mild cognitive impairment. In addition to conventional brain imaging, the team measured the participants’ cerebral blood flow using a velocity encoding MRI-technique that can be easily implemented in most MRI scanners and takes less than two minutes to scan. In addition, assessment of performance levels of several cognitive domains was also evaluated. Comparisons and associations were investigated using analyses of covariance and linear regression.

Black and white brain scan
Measurement of tCBF using MRI in an early aMCI subject. 1a. Maximum projection intensity (MIP) image of the neck arteries showing the location of the imaging plane (green line). 1b. One of the velocity-encoded images with the segmented vessel lumens shown in red. 1c. The derived tCBF waveform over the cardiac cycle.

Total CBF was significantly reduced in the subjects who were at the early phase of cognitive impairment, while the volumes of the cognitively critical brain region were not. “We were somewhat surprised to find a significant reduction in global CBF and perfusion while brain volumes were within the normative values in the very early phase of AD,” Dr. Alperin said.

These findings imply that reduced total CBF is a stronger biomarker of the early phase of Alzheimer’s disease than volumes of AD-prone brain regions.

Providing input on the manuscript were James E. Galvin, M.D., M.P.H., a professor of neurology, psychology, and behavioral sciences; Bonnie Levin, Ph.D., professor of neurology; and Alexander McKinney, M.D., professor of radiology.

“Next, we will be reapplying for internal seed funding to add measurements of amyloid beta and tau in parallel to measurements of total CBF and tissue loss to enhance the phenotyping of our subjects as preclinical AD,” Dr. Alperin said. “We believe our study will encourage a wider use of total CBF measurements for early detection of Alzheimer’s disease, where reduction in total CBF and global perfusion occur prior to excessive brain atrophy.”

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