The diagnostic accuracy of [¹⁸F]FDG-PET for discriminating LBD from APS is considerably higher than for [¹²³I]IBZM-SPECT. [¹⁸F]FDG-PET reliably differentiates APS subgroups.

Clinical Alzheimer's disease affects both cerebral hemispheres to a similar degree in clinically typical cases. However, in atypical variants like logopenic progressive aphasia, neurodegeneration often presents asymmetrically. Yet, no in vivo imaging study has investigated whether lateralized neurodegeneration corresponds to lateralized amyloid-β burden. Therefore, using combined (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography, we explored whether asymmetric amyloid-β deposition in Alzheimer's disease is associated with asymmetric hypometabolism and clinical symptoms. From our database of patients who underwent positron emission tomography with both (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose (n = 132), we included all amyloid-positive patients with prodromal or mild-to-moderate Alzheimer's disease (n = 69). The relationship between (11)C-Pittsburgh compound B binding potential and (18)F-fluorodeoxyglucose uptake was assessed in atlas-based regions of interest covering the entire cerebral cortex. Lateralizations of amyloid-β and hypometabolism were tested for associations with each other and with type and severity of cognitive symptoms. Positive correlations between asymmetries of Pittsburgh compound B binding potential and hypometabolism were detected in 6 of 25 regions (angular gyrus, middle frontal gyrus, middle occipital gyrus, superior parietal gyrus, inferior and middle temporal gyrus), i.e. hypometabolism was more pronounced on the side of greater amyloid-β deposition (range: r = 0.41 to 0.53, all P < 0.001). Stronger leftward asymmetry of amyloid-β deposition was associated with more severe language impairment (P < 0.05), and stronger rightward asymmetry with more severe visuospatial impairment (at trend level, P = 0.073). Similarly, patients with predominance of language deficits showed more left-lateralized amyloid-β burden and hypometabolism than patients with predominant visuospatial impairment and vice versa in several cortical regions. Associations between amyloid-β deposition and hypometabolism or cognitive impairment were predominantly observed in brain regions with high amyloid-β load. The relationship between asymmetries of amyloid-β deposition and hypometabolism in cortical regions with high amyloid-β load is in line with the detrimental effect of amyloid-β burden on neuronal function. Asymmetries were also concordant with lateralized cognitive symptoms, indicating their clinical relevance.

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[F-18]-FDG-PET could reveal syndrome-specific patterns of glucose metabolism in PCA and DLB. Accurate group discrimination in the differential diagnosis of dementia with visuospatial impairment is feasible.

Early prognostic stratification is desirable in patients with suspected atypical parkinsonian syndromes (APSs) for optimal treatment and counseling. We investigated the prognostic value of imaging diseasespecific metabolism patterns with 18 F-FDG PET compared with that of clinical diagnosis. Methods: Seventy-eight patients with suspected APS at study inclusion underwent a follow-up of up to 5.9 y after prospective 18 F-FDG PET imaging. Survival data were analyzed by Kaplan-Meier and Cox regression analyses according to diagnostic classifications provided by 18 F-FDG PET at baseline and clinical diagnoses after a median follow-up of 1 y after PET. Results: Forty-four of 78 patients were alive 4.7 ± 0.6 y after PET. Patients diagnosed with an APS by PET or 1-y clinical follow-up showed a significantly shorter median survival time (4.1 y, age-adjusted hazard ratios [HRs] 5 3.8 for both classifiers) than those diagnosed with Lewy-body diseases (LBDs; majority Parkinson disease [PD]; median survival time not reached). Subgroup classifications of progressive supranuclear palsy/ corticobasal degeneration (PSP/CBD) or multiple-system atrophy (MSA) by PET and clinical follow-up were associated with significantly shorter survival than PD. Age-adjusted mortality was significantly increased for PSP/CBD (HR 5 5.2) and MSA (HR 5 5.6) classified by PET, but for PSP/CBD only when diagnosed by clinical follow-up (HR 5 4.5). Patients with a PET pattern suggestive of PD with dementia/dementia with Lewy bodies (PDD/DLB) exhibited a trend toward shorter survival than those with PD (P 5 0.07), whereas patients classified as PDD/DLB by clinical follow-up did not (P 5 0.65). Conclusion: 18 F-FDG PET is an early predictor of survival in patients with clinically suspected APS. Detection of cortical or subcortical hypometabolism by 18 F-FDG PET is an unfavorable predictor. Risk stratification by 18 F-FDG PET appears to be at least as predictive as the 1-y follow-up clinical diagnosis. This finding strongly supports the early inclusion of PET imaging in patient care.