ASL perfusion MRI predicts cognitive decline and conversion from MCI to dementia

Abstract

We compared the predictive value of cerebral perfusion as measured by arterial-spin labeling magnetic resonance imaging (ASL-MRI) with MRI-derived hippocampal volume for determining future cognitive and functional decline and subsequent conversion from mild cognitive impairment to dementia. Forty-eight mild cognitive impairment subjects received structural and ASL-MRI scans at baseline and clinical and neuropsychologic assessments annually. Thirteen subjects became demented during the period of longitudinal observation (2.7+/-1.0 y). Cox regression analyses suggest that baseline hippocampal volume [relative risk (RR)=0.99, P=0.004], baseline right inferior parietal (RR=0.64, P=0.01) and right middle frontal (RR=0.73, P=0.01) perfusion were associated with conversion to dementia. Results from linear mixed effects modeling suggest that baseline perfusion from the right precuneus predicted subsequent declines in Clinical Dementia Rating Sum of Boxes (P=0.002), Functional Activates Questionnaire (P=0.01), and selective attention (ie, Stroop switching, P=0.009) whereas baseline perfusion from the right middle frontal cortex predicted subsequent episodic memory decline (ie, total recognition discriminability score from the California Verbal Learning Test, P=0.03). These results suggest that hypoperfusion as detected by ASL-MRI can predict subsequent clinical, functional, and cognitive decline and may be useful for identifying candidates for future Alzheimer disease treatment trials.

FIGURE 1

Statistical parametric maps showing regions of hypoperfusion in the 13 mild cognitive impairment subjects who converted to dementia relative to the 35 mild cognitive impairment subjects who remain nondemented. Converters had hypoperfusion in the right precuneus/posterior cingulum (shown in the sagittal and axial slices), right middle cingulum (shown in the sagittal and coronal slices), right middle frontal cortex (shown in the coronal slice), and right inferior parietal cortex (shown in the axial slice). The shaded areas in the sagittal and coronal slices represent regions not covered by our implementation of arterial-spin labeling magnetic resonance imaging.

FIGURE 2

Scatter plots of the subjects' California Verbal Learning Test total recognition discriminability scores as a function of time.

FIGURE 3

Scatter plots of the subjects' Delis Kaplan Executive Function System-Stroop switching (scaled) scores as a function of time.

FIGURE 4

Scatter plots of the subjects' Clinical Dementia Rating Scale sum of boxes scores as a function of time.

FIGURE 5

Scatter plots of the subjects' Functional Activates Questionnaire scores as a function of time.