title: Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies.
abstract: Cerebral glucose metabolism using positron emission tomography (PET) with (18)F-fluorodeoxyglucose was examined in 11 patients with probable Alzheimer's disease (AD), 6 patients with probable, and 1 patient with autopsy-confirmed dementia with Lewy bodies (DLB) as well as in 10 age-matched normal control subjects. Among widespread cortical regions showing glucose hypometabolism in the DLB group, the metabolic reduction was most pronounced in the visual association cortex compared to that in the AD group. Using a metabolic ratio of 0.92 in the visual association cortex as a cutoff (mean-2 SD of normal control subjects), DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91%. In contrast, apolipoprotein E4 allele frequency and cerebrospinal fluid tau levels did not differ significantly between the two groups. In order to further dissect out neuropathological correlates of the dysfunctional occipital lobe, postmortem brains from 19 patients with AD and 17 with DLB as well as 11 brains from normal controls were examined. A distinct and extensive spongiform change with coexisting gliosis was variably noted throughout cerebral white matter with relative sparing of gray matter in DLB. Notably, the white matter spongiform change and gliosis was most prominently and consistently found in the occipital region of DLB, and the severity of the spongiform change in each brain region generally paralleled to the regional difference in reduced glucose metabolism between the living AD and DLB patients. These findings suggest that (1) among several potential antemortem biomarkers in the diagnosis of DLB, measures of the glucose metabolism in the occipital cortex may be an informative diagnostic aid to distinguish DLB from AD; and (2) a pathological process that generates widespread spongiform change and gliosis in long projection fibers may contribute, at least in part, to the characteristic imaging features of DLB.
authors.affiliation: Department of Geriatric Medicine, Tohoku University School of Medicine, Miyagi, Sendai, 980, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Higuchi
authors.forename: M
authors.initials: M
authors.lastname: Tashiro
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: N
authors.initials: N
authors.lastname: Okamura
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: R W
authors.initials: RW
authors.lastname: Shin
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D019788:Fluorodeoxyglucose F18; D005787:Gene Frequency; D005911:Gliosis / Q000175:diagnosis / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009778:Occipital Lobe / Q000378:metabolism; D012680:Sensitivity and Specificity; D051843:Synucleins; D014055:Tomography, Emission-Computed; D014452:Ubiquitins / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins; D051843:Synucleins; D014452:Ubiquitins; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose