Jack, Clifford R.

Objectives To determine the cross‐sectional association between cerebral amyloid‐beta (A β ) deposition and gait. Design Cross‐sectional. Setting Population‐based cohort study in Olmsted County, MN . Participants Cognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB‐ PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. Measurements PiB‐ PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor‐specific regions of interest ( ROI s). Gait parameters (speed, cadence, stride length, double support time, and intra‐individual stance time variability) were measured using GAITR ite ® instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE ε 4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR , and cortical thickness) in AD ‐associated regions. Results In fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB‐ PET SUVR across all ROI s was associated with slower gait speed ( P < .05 except for the parietal ROI ), lower cadence and longer double support time ( P ≤ .05 except for the motor ROI ), and greater stance time variability ( P < .05). In sex‐stratified analyses, the association between higher PiB‐ PET SUVR across all ROI s and measures of gait was only present among women. Conclusion PiB‐ PET SUVR across ROI s, independent of general measures of AD ‐associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether A β predicts gait decline in both women and men.

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.