COMPARISON OF POSITRON EMISSION TOMOGRAPHY, COGNITION, AND BRAIN VOLUME IN ALZHEIMERS-DISEASE WITH AND WITHOUT SEVERE ABNORMALITIES OF WHITE-MATTER

Objectives-To examine cerebral metabolism, cognitive performance, and brain healthy patients Alzheimer's disease, one group with severe abno rmalities of white matter (DAT+) and the other group with none, or min imal abnormalities (DAT-). Methods-Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. Results-Co mpared with the healthy controls, both demented groups had significant ly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typi cal of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performa nce were significantly correlated in the DAT- patient group. Compariso n of DAT+ with DAT- patients showed a significantly higher ratio of pa rietal to whole brain glucose utilisation for the DAT+ group. Moreover , when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in t he frontal, parietal, and temporal regions than did the DAT- group. Di scriminant analysis using metabolic ratios of the frontal, parietal, a nd temporal regions showed cerebral metabolic patterns to be significa ntly different among the DAT+, the DAT-, and the healthy controls. The se differences were due primarily to relatively higher frontal, pariet al, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls an d the DAT- group. Group mean scores on tests of neuropsychological per formance were not significantly different between the DAT- and DAT+ pa tients. By contrast with the DAT- group, however, no significant corre lations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant be tween group differences in the relation between the AD ratio and neuro psychological scores on three tasks. The slopes of the relations betwe en the AD ratio and memory scores (memory and freedom from distractabi lity deviation quotient of the Wechsler adult intelligence scale (WMDQ )) also were significantly different for the two groups. Conclusions-A lthough multiple causes for abnormalities of white matter exist in pat ients with Alzheimer's disease, these data suggest that the presence o f severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-te mporal metabolic deficits and correlations between association neocort ical metabolism and neuropsychological task performance typical of pat ients with Alzheimer's disease. By contrast, the DAT+ group had a patt ern of cerebral metabolism significantly different from healthy contro ls and DAT+ patients, as well as no significant correlations between m etabolism in the association neocortex and neuropsychological performa nce. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.