Spychalla, Anthony J.

ObjectivePatients with probable dementia with Lewy bodies (DLB) often have Alzheimer's disease (AD)‐related pathology. Our objective was to determine the pattern of positron emission tomography (PET) tau tracer AV‐1451 uptake in patients with probable DLB, compared to AD, and its relationship to β‐amyloid deposition on PET.MethodsConsecutive patients with clinically probable DLB (n = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic resonance imaging, AV‐1451, and Pittsburgh compound‐B (PiB) PET examinations. Age‐ and sex‐matched groups of AD dementia (n = 19) patients and clinically normal controls (n = 95) from an epidemiological cohort served as a comparison groups. Atlas‐ and voxel‐based analyses were performed.ResultsThe AD dementia group had significantly higher AV‐1451 uptake than the probable DLB group, and medial temporal uptake completely distinguished AD dementia from probable DLB. Patients with probable DLB had greater AV‐1451 uptake in the posterior temporoparietal and occipital cortex compared to clinically normal controls, and in probable DLB, the uptake in these regions correlated with global cortical PiB uptake (Spearman rho = 0.63; p = 0.006).InterpretationMedial temporal lobe AV‐1451 uptake distinguishes AD dementia from probable DLB, which may be useful for differential diagnosis. Elevated posterior temporoparietal and occipital AV‐1451 uptake in probable DLB and its association with global cortical PiB uptake suggest an atypical pattern of tau deposition in DLB. ANN NEUROL 2017;81:58–67

ABSTRACTBackgroundThe [18F]AV‐1451 positron emission tomography ligand allows the in vivo assessment of tau proteins in the brain. It shows strong binding in Alzheimer's dementia, but little is known about how it performs in progressive supranuclear palsy, a primary 4R tauopathy.ObjectivesThe objectives of this study were to determine whether [18F]AV‐1451 uptake can be observed in progressive supranuclear palsy and to characterize the regional distribution when compared with controls and Alzheimer's dementia.Methods[18F]AV‐1451 positron emission tomography was performed in 10 patients with probable progressive supranuclear palsy. These patients were age‐ and gender‐matched to 50 controls and 10 Alzheimer's dementia patients who had undergone identical [18F]AV‐1451 imaging. Regional comparisons of [18F]AV‐1451 uptake were performed across the whole brain using region‐of‐interest and voxel‐level analyses, and correlations between regional [18F]AV‐1451 and the progressive supranuclear palsy rating scale were assessed.ResultsAn elevated [18F]AV‐1451 signal was observed in progressive supranuclear palsy when compared with controls in the pallidum, midbrain, dentate nucleus of the cerebellum, thalamus, caudate nucleus, and frontal regions. Signal in the cerebellar dentate and pallidum were also greater in progressive supranuclear palsy when compared with Alzheimer's dementia. Conversely, the [18F]AV‐1451 signal across the cortex was higher in Alzheimer's dementia when compared with progressive supranuclear palsy. The [18F]AV‐1451 signal in a number of regions correlated with the progressive supranuclear palsy rating scale.ConclusionsProgressive supranuclear palsy is associated with an elevated [18F]AV‐1451 signal in a characteristic and distinct regional pattern that correlates with disease severity and differs from the patterns observed in Alzheimer's dementia. © 2016 International Parkinson and Movement Disorder Society.

ABSTRACTBACKGROUND AND PURPOSEMild cognitive impairment (MCI) precedes both Alzheimer's disease (AD) dementia and with Lewy bodies (DLB). We investigated proton magnetic resonance spectroscopy (MRS) characteristics of MCI patients who progressed to DLB compared to those who progressed to AD dementia or remained stable.METHODSConsecutive MCI patients who underwent single voxel MRS at baseline and progressed to DLB (n = 10) were identified during a median follow‐up period of 18 months. From the same cohort, we identified age‐ and sex‐matched MCI patients who progressed to AD dementia (n = 27) or remained stable (n = 20) during a similar follow‐up period. This study was approved by the Institutional Review Board and informed consent was from every subject.RESULTSMCI patients who progressed to AD dementia were characterized by lower N‐acetylaspartate (NAA)/Cr ratio in the posterior cingulate voxel compared to those who progressed to DLB (P = .001). Decreased NAA/Cr in the posterior cingulate voxel differentiated MCI patients who progressed to DLB from those who progressed to AD with an area under the receiver operating characteristic curve of .85 (P < .001) on logistic regression analysis.CONCLUSIONSMRS may be useful in differentiating MCI patients with prodromal AD dementia from those with prodromal DLB for early disease‐specific interventions.