Abstract
PurposeTo assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to Alzheimer’s disease.MethodsWe assessed tau aggregates with [18F]AV1451 PET, amyloid-β depositions with [18F]AV45 PET, and volumetric microstructural changes with MRI. We validated for [18F]AV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of [18F]AV1451 binding.ResultsCBS patients showed increases in [18F]AV1451 SUVRs in parietal (P < 0.05) and frontal (P < 0.05) cortices in the affected hemisphere compared to healthy controls and in precentral (P = 0.008) and postcentral (P = 0.034) gyrus in the affected hemisphere compared to MCI patients. Our data were confirmed at the histopathological level in one CBS patient who underwent brain biopsy and showed sparse tau pathology in the parietal cortex co-localizing with increased [18F]AV1451 signal. Cortical and subcortical [18F]AV45 uptake was within normal levels in CBS patients. In parietal and frontal cortices of the most affected hemisphere we found also grey matter loss (P < 0.05), increased mean diffusivity (P < 0.05) and decreased fractional anisotropy (P < 0.05) in CBS patients compared to healthy controls and MCI patients. Grey matter loss and white matter changes in the precentral gyrus of CBS patients were associated with worse motor symptoms.ConclusionsOur findings demonstrate disease-related patterns of in vivo tau and microstructural pathology in the absence of amyloid-β, which distinguish CBS from non-affected individuals and MCI patients.
Highlights
Corticobasal syndrome (CBS) is a rare sporadic neurodegenerative disorder clinically characterised by asymmetric rigidity and apraxia with other features such as cortical sensory loss, alien limb behaviour, conjugate ocular movement abnormalities, bradykinesia, myoclonus and dementia [1].Eur J Nucl Med Mol Imaging (2018) 45:2413–2425The core neuropathological feature of corticobasal degeneration is abnormal accumulation of hyperphosphorylated 4repeat tau (4R) in the form of neurofibrillary tangles, neuropil threads and coiled bodies together with astrocytic plaques [2]
CBS patients performed worse than healthy controls in the assessments of psychomotor speed [five choice median reaction time (P = 0.011) and median movement time (P = 0.017)], attention [rapid visual information processing Atime (P = 0.048) and median latency (P = 0.009)] and episodic memory [delayed match to sample % correct (P = 0.032) and probability of given error (P = 0.004); Table S2]
No significant differences were found between mean cortical [18F]AV1451 standardised uptake value ratio 60–80 (SUVR) and [18F]AV1451 Logan distribution volume ratio (DVR) in our group of CBS patients (Table S3) and healthy controls
Summary
Corticobasal syndrome (CBS) is a rare sporadic neurodegenerative disorder clinically characterised by asymmetric rigidity and apraxia with other features such as cortical sensory loss, alien limb behaviour, conjugate ocular movement abnormalities, bradykinesia, myoclonus and dementia [1].Eur J Nucl Med Mol Imaging (2018) 45:2413–2425The core neuropathological feature of corticobasal degeneration is abnormal accumulation of hyperphosphorylated 4repeat tau (4R) in the form of neurofibrillary tangles, neuropil threads and coiled bodies together with astrocytic plaques [2]. An in vivo [18F]AV1451 PET study has shown increased tau uptake in the motor cortex, corticospinal tract, and basal ganglia in the hemisphere contralateral to the most affected body side of six patients with CBS compared to healthy controls and patients with AD and PSP [8]. Another [18F]AV1451 PET study has demonstrated increased tau binding in the putamen, globus pallidus, thalamus and precentral grey and white matter in the hemisphere contralateral to the clinically most affected side in six CBS patients [9]. Previous MRI studies have shown grey matter loss and white matter changes in precentral, superior frontal, and fusiform gyri, putamen and globus pallidus in CBS patients [10, 11]
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