Brain Deactivation May Be MRI Marker of Early Alzheimer's

CHAPEL HILL, N.C., Sept. 25 -- A sensitive sign of the early stages of Alzheimer's disease may be dampening of activity in the posteromedial cortices during a memory task, as seen by functional MRI, investigators here suggested.

In a study comparing functional MRI scans of healthy volunteers with those of patients with mild cognitive impairment or mild Alzheimer's disease, the degree of activation of the posteromedial cortices correlated significantly with scores on a verbal learning test, reported Jeffrey R. Petrella, M.D., of Duke, and colleagues.

Deactivation of the posteromedial cortices during novel or familiar facial encoding tasks could be a more sensitive marker for early-stage Alzheimer's than activation of other areas, the authors wrote in the October issue of Radiology.

"The findings of this study implicate a potential functional, rather than structural, brain marker -- separate from atrophy -- that may help enhance diagnosis and treatment monitoring of Alzheimer's patients," Dr. Petrella said.

He and his colleagues devised a study to prospectively identify which brain regions would be activated on functional MRI scans during memory tasks, and to see whether those changes correlated with memory impairment patients across the spectrum from cognitively intact to mildly demented.

They enrolled 75 men and women, mean age 72.9 + 7.2 into the study. Thirteen of the patients had a diagnosis of mild Alzheimer's disease, 34 had amnestic mild cognitive impairment, and 28 served as healthy controls.

The patients underwent functional MRI scan in a 4.0 Tesla magnet while they performed novel encoding and familiar encoding of face-name pairs.

The investigators assessed blood oxygen level-dependent changes across the entire brain for each group of participants.

They also conducted between-subject analyses to identify brain regions that demonstrated either a monotonic increase or decrease in activation magnitude, and correlated the blood oxygen level-dependent changes scores on the delayed portion of the California Verbal Learning Test.

They found that the controls had greater activation during novel encoding tasks than in familiar encoding tasks in the dorsolateral prefrontal, lateral parietal, and medial temporal regions. Controls also had deactivation, or reduced activity, that was greater during familiar encoding than in novel encoding in the midline frontal and parietal regions.

"Along the spectrum from control subjects to patients with Alzheimer's disease, there was decreasing activation in the medial temporal lobe, including the hippocampus and parahippocampal and fusiform gyri, and increasing activation in the posteromedial cortices primarily in the precuneus and posterior cingulate gyrus," the authors wrote.

When they compared the verbal learning scores with the images, they found that the magnitude of activation in the posteromedial corticies correlated significantly with scores (P<0.001, r=-0.502).

"Compared with activation in the medial temporal lobe, deactivation in the posteromedial cortices could be a more sensitive marker of early Alzheimer's disease at functional magnetic resonance imaging," they wrote.

The authors noted several limitations of the study.

• They cited a differential loss rate of participants from the initial recruiting pool (total 23.5% [23 of 98], control group 17.6% [six of 34], mild cognitive impairment group 22.7% [10 of 44], and Alzheimer's disease group 35% [seven of 20]). "It is therefore possible that subjects were not lost at random (e.g., exclusion for excessive motion may have been more prevalent in the Alzheimer's disease group)."
• There was also a "significant difference in education levels between subject groups," with the mild Alzheimer's group having significantly fewer years of education.