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.

Event-related potentials and behavioral measures were obtained from young and elderly subjects while they performed two different auditory delayed match-to-sample tasks. In each experiment, subjects had to indicate whether an initial and a subsequent test sound were identical in two different conditions: one filled with distracting tone pips and one with no distractors. Electrophysiologically, elderly subjects had reduced attention-related activity over frontal regions. In addition, the distracting stimuli elicited an enhanced primary auditory evoked response in the elderly. The percentage of perseverative errors on the Wisconsin card sorting test, a putative measure of frontal lobe function, was positively correlated with the amplitude of the primary auditory evoked response in elderly subjects. Behaviorally, elderly subjects were impaired by distractors at long but not short delays. Taken together, these results suggest that increased distractibility and impaired sustained attention with aging may be due to altered prefrontal cortex function. These data support the loss of prefrontal suppression over the primary auditory regions with aging.