Correlation With Clinical Parameters

Numerous PET and SPECT studies have reported good correlations between the degree of metabolic or perfusion abnormality and dementia severity (15,16,28,29). Most of these studies utilize standard global assessment

Fig. 1. Brain perfusion SPECT images. (Left) Normal control subject. (Center) Patient with Alzheimer's disease, showing reduced perfusion is most prominent in the association cortex of the parietal lobes (arrows). (Right) Quantitative group differences in perfusion are shown superimposed on the AD patient's image. Filled in areas represent those regions significantly reduced in Alzheimer's disease (n = 29) compared to age-matched control (n = 64; p < 0.00l). When parietal perfusion is used to discriminate all subjects (using split-half replication), the accuracy of SPECT is 92%.

Fig. 1. Brain perfusion SPECT images. (Left) Normal control subject. (Center) Patient with Alzheimer's disease, showing reduced perfusion is most prominent in the association cortex of the parietal lobes (arrows). (Right) Quantitative group differences in perfusion are shown superimposed on the AD patient's image. Filled in areas represent those regions significantly reduced in Alzheimer's disease (n = 29) compared to age-matched control (n = 64; p < 0.00l). When parietal perfusion is used to discriminate all subjects (using split-half replication), the accuracy of SPECT is 92%.

tests such as the Mini-Mental State Examination (MMSE), the Blessed Dementia Scale, or the Mattis Dementia Rating Scale (30).

Foster and colleagues (31) examined a group of patients with moderate-to-severe AD with focal neuropsychological syndromes, and demonstrated hy-pometabolism in left perisylvian regions in patients with predominate language abnormalities and hypometabolism in right posterior parietal regions in patients with predominant visuospatial deficits. Haxby and colleagues (22) also found the lateral asymmetry of cerebral glucose metabolism was associated with relative degree of language and visuospatial impairments in early AD. In another study, Haxby and colleagues (32) reported that the parietal/frontal metabolic ratios correlated significantly with neuropsychological deficits in patients with moderate AD. Patients with "disproportionate" parietal hypometabolism showed impairment of verbal comprehension, calculation, and visuospatial functions, while patients with "disproportionate" frontal hypometabolism showed impairment of verbal fluency and attention. These functional imaging findings are consistent with hypotheses about the localization of brain-behavior relationships (33).

Variation in functional patterns also may be correlated with the psychiatric and behavioral aspects of AD. Craig and associates (34) recently reported that the presence of apathy in patients with AD was correlated with prefrontal and anterior temporal hypoperfusion, and not with posterior temporal or parietal hypoperfusion. Starkstein and coworkers (35) used SPECT to study 16 AD

patients with delusions and 29 AD patients without delusions. The patients with delusions had significantly lower cerebral blood flow than patients without delusions in left and right temporal regions, but no significant differences between in frontal, parietal, basal ganglionic, or thalamic blood flow.

Recently, several investigators have examined the relationship between cerebral perfusion or metabolism and premorbid abilities. Stern and coworkers (36) reported that after controlling for dementia severity, higher level of education in patients with AD was associated with greater reductions in pari-etotemporal perfusion. Alexander and associates (37) found that higher pre-morbid intellectual ability in individuals, with the same degree of dementia, was associated with lower metabolic rates in several frontal regions and left superior parietal association areas. These studies suggest that a greater burden of pathology may be required to manifest the same level of impairment in individuals with higher education or intellectual capabilities, and support the hypothesis that "cognitive reserve" may affect the clinical expression of dementia. These findings may have significant implications for the "preclinical" diagnosis of AD with functional imaging.

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