Table 2.
Characteristics of enrolled studies detecting CCD in neurodegenerative diseases.
| Authors | Sample Size | Age Range | Study Center (Site) | Imaging Modality | Parameters | Main Results | Study Design |
|---|---|---|---|---|---|---|---|
| (Tripathi et al., 2022 [7]) | 830 AD patients | Mean age = 70.72 | Multicentric | [18F]-FDG-PET | 18F-FDG-PET Quantification of FDG-PET hypometabolism was carried out using a standardized uptake value ratio (SUVR), with pons as the comparison region. |
There were significant differences in the SUVR in different brain regions including temporal, occipital, and cerebellar cortices with right and left asymmetry. The SUVR was lower in the left temporal and occipital regions, whereas the SUVR was lower in the right side of the cerebellum. | Retrospective |
| (HERTEL et al., 2021 [10]) | 65 (43.1% females, 56.9% males) | 51–88 (mean = 74) |
NA | MRI (ASL PWI) |
Pulsed ASL PWI with field of view 256 × 256, acquisition matrix 64 × 64, number of slices 9, slice thickness 8 mm, echo time 11 ms, repetition time 2500 ms, number of averages: 1, and duration 5:57 min. | A total of 65 patients were included in the study and 22 (33.8%) patients were found to be CCD-positive. CCD-positive patients had a significantly smaller whole brain volume (862.8 ± 49.9 vs. 893.7 ± 62.7 mL, and p = 0.049) and white matter volume (352.9 ± 28.0 vs. 374.3 ± 30.7, and p = 0.008) in comparison to CCD negative patients. Conclusion: ASL PWI was able to detect CCD in approximately one-third of patients with AD and was associated with smaller whole brain and white matter volume. |
Retrospective |
| (Provost et al., 2021 [18]) | 197 (39% male) | 22–90 (mean = 67) | At the Memory and Aging Center, University of California San Francisco (UCSF), | [18F]FDG-PET PET PET/CT |
|
Cerebellar 18F-FDG asymmetry was associated with reverse asymmetry of 18F-FDG in the cerebral cortex (especially frontal and parietal areas) and basal ganglia. Significant CCD was present in 47/197 (24%) patients and was most frequent in corticobasal syndrome and semantic and logopenic variants of primary progressive aphasia. Mediation analysis in β-amyloid-positive patients had 18F-Flortaucipir cortical asymmetry and it was associated with cerebellar 18F-FDG asymmetry. | Retrospective |
| (Franceschi et al., 2021 [6]) | 75 (31 M, 44 F), | mean age = 74 | Manhasset Images were obtained with an integrated 3-T PET/MRI system. PET surface maps, fused T1-weighted magnetization-prepared rapid acquisition gradient echo, and axial FLAIR/PET images were generated with a postprocessing software |
Hybrid Imaging (FDG-PET/MRI), 2 blinded radiologists, and a nuclear medicine physician evaluated the PET/MRI images for pattern of neurodegenerative diseases. |
IV injection FDG was administered for brain imaging in a 3-T PET/MRI system). A dual-echo T1-weighted gradient-recalled echo sequence was performed to acquire the MRI attenuation-correction map based on Dixon segmentation. The PET image matrix size was 344 × 344 × 127 mm, and transaxial voxel dimensions were 1.04 × 1.04 mm with a thickness of 2.03 mm. | Qualitative assessment showed that 10 of 75 (7.5%) patients had decreased metabolism in the cerebellar hemisphere contralateral to the supratentorial cortical hypometabolism consistent with CCD. Six of the ten patients had characteristic imaging findings of frontotemporal dementia (three behavioral variant frontotemporal dementia, two semantic primary progressive aphasia, and one logopenic primary progressive aphasia), three had suspected corticobasal degeneration, and one had Alzheimer dementia. Results of the study revealed that frontotemporal dementia, particularly the behavioral variant, and in patients with cortico-basal degeneration. |
Retrospective |
| (Reesink et al., 2018 [11]) | 4 subjects | NA | NA | [18F]-FDG-PET&11C-PiB-PET | combination of 18F-FDG PET and 11C-PiB PET imaging | 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer in the left hemisphere. Thus, the CCD could be explained on the functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment. | Retrospective study |
| (Akiyama et al., 1989 [16]) | 26 patients | NA | NA | [18F]FDG-PET | Asymmetry indices (AIs) of cerebral metabolic rates for matched left-right regions of interest (ROIs) were calculated and the extent of diaschisis by correlative analyses was ascertained. For the Alzheimer group, cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices, while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and the cerebral hemisphere. Crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer’s disease by positron emission tomography (PET) using 18F-fluorodeoxyglucose was detected in the study. These data indicate that PET is a sensitive technique for detecting diaschisis. | Retrospective | |
| (Tanaka et al., 1993 [27]) | 26 (4 patients with dementia + Amylotrophic lateral sclerosis (ALS), 9 patients with ALS but without dementia, and 13 healthy.) | NA | NA | PET | Positron emission tomography with oxygen-15 gas and oxygen-15 labelled carbon dioxide | The mean regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen metabolism (rCMRO2) in the anterior cerebral hemispheres decreased significantly in patients with progressive dementia with ALS, while patients with only ALS showed very mild reductions of rCBF and rCMRO2, which were not statistically significant in comparison to controls. Thus, the hypoperfusion and oxygen hypometabolism in the anterior cerebral hemispheres have an etiological relationship to cognitive impairment in patients with progressive dementia with ALS. A similar reduction in the mean rCBF was also found in the cerebellar hemispheres in progressive dementia with ALS, which was statistically significant, while a reduction in mean rCMRO2 was not significant. Remote effects analogous to crossed cerebellar diaschisis occurring bilaterally were assumed to explain the cerebellar hypoperfusion. | |
| (Al-Faham et al., 2014 [28]) | 1 old man | 71 years | Michigan, USA | 18FFDG-PET | After intravenous administration of of 18F-FDG, multiple tomographic slices of the brain were obtained with the 18F-FDG PET scan | An 18F-FDG PET scan demonstrated decreased radiotracer activity in the left and right parietal lobes, as well as left temporal and occipital lobes, which is compatible with Lewy body dementia. Moreover, there was decreased radiotracer uptake in the right cerebellum, suggestive of CCD. | Retrospective |