Dataset Information

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

ABSTRACT: Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease.Flortaucipir and florbetapir (?-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and ?-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age.PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients.Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

SUBMITTER: Day GS

PROVIDER: S-EPMC5443698 | biostudies-literature | 2017 Apr-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

Day Gregory S GS Gordon Brian A BA Jackson Kelley K Christensen Jon J JJ Rosana Ponisio Maria M Su Yi Y Ances Beau M BM Benzinger Tammie L S TLS Morris John C JC

Alzheimer disease and associated disorders 20170401 2

<h4>Background</h4>Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease.<h4>Methods</h4>Flortaucipir and florbetapir (β-amyloid) PET imaging were perfor ...[more]

PMID: 28394771

Similar Datasets

Project description:Heterogeneity within the Alzheimer's disease (AD) syndromic spectrum is typically classified in a domain-specific manner (e.g., language vs. visual cognitive function). The central aim of this study was to investigate whether impairment in visual cognitive tasks thought to be subserved by posterior cortical dysfunction in non-amnestic AD presentations is associated with tau, amyloid, or neurodegeneration in those regions using 18F-AV-1451 and 11C-PiB positron emission tomography (PET) and magnetic resonance imaging (MRI). Sixteen amyloid-positive patients who met criteria for either Posterior Cortical Atrophy (PCA; n = 10) or logopenic variant Primary Progressive Aphasia (lvPPA; n = 6) were studied. All participants underwent a structured clinical assessment, neuropsychological battery, structural MRI, amyloid PET, and tau PET. The neuropsychological battery included two visual cognitive tests: VOSP Number Location and Benton Facial Recognition. Surface-based whole-cortical general linear models were used to first explore the similarities and differences between these biomarkers in the two patient groups, and then to assess their regional associations with visual cognitive test performance. The results show that these two variants of AD have both dissociable and overlapping areas of tau and atrophy, but amyloid is distributed with a stereotyped localization in both variants. Performance on both visual cognitive tests were associated with tau and atrophy in the right lateral and medial occipital association cortex, superior parietal cortex, and posterior ventral occipitotemporal cortex. No cortical associations were observed with amyloid PET. We further demonstrate that cortical atrophy has a partially mediating effect on the association between tau pathology and visual cognitive task performance. Our findings show that non-amnestic variants of AD have partially dissociable spatial patterns of tau and atrophy that localize as expected based on symptoms, but similar patterns of amyloid. Further, we demonstrate that impairments of visual cognitive dysfunction are strongly associated with tau in visual cortical regions and mediated in part by atrophy.

Project description:See Gordon (doi:10.1093/brain/awy052) for a scientific commentary on this article.Predicting underlying pathology based on clinical presentation has historically proven difficult, especially in older cohorts. Age-related hippocampal sclerosis may account for a significant proportion of elderly participants with amnestic dementia. Advances in molecular neuroimaging have allowed for detailed biomarker-based phenotyping, but in the absence of antemortem markers of hippocampal sclerosis, cases of mixed pathology remain problematic. We evaluated the utility of 18F-FDG-PET to differentiate flortaucipir tau PET negative from flortaucipir positive amnestic mild cognitive impairment and dementia and used an autopsy confirmed cohort to test the hypothesis that hippocampal sclerosis might account for the observed pattern. We identified impaired participants (Clinical Dementia Rating > 0) with amnestic presentations ≥ 75 years who had MRI and PET imaging with 18F-FDG (glucose metabolism), Pittsburgh compound B (amyloid) and flortaucipir (tau) performed within a year of cognitive assessment. These were stratified into amyloid positive/negative and tau positive/negative according to the A/T/N classification scheme. Our sample included 15 amyloid and tau-positive participants, and nine tau-negative participants (five of whom were amyloid-positive). For the autopsy cohort, sequential cases with antemortem 18F-FDG-PET were screened and those with TDP-43-negative Alzheimer's disease (10 cases) and TDP-43-positive hippocampal sclerosis (eight cases) were included. We compared each group to controls and to each other in a voxel-based analysis, and supplemented this with a region of interest-based analysis comparing medial to inferior temporal metabolism. Tau-positive and negative cases did not differ on neuropsychological testing or structural magnetic resonance biomarkers. Tau-negative cases had focal medial temporal and posterior cingulate/retrosplenial hypometabolism regardless of amyloid status, whereas tau-positive cases had additional lateral parietal and inferior temporal involvement. The inferior/medial temporal metabolism ratio was significantly different between the groups with the tau-negative group having a higher ratio. In the autopsy series, hippocampal sclerosis cases had greater medial temporal hypometabolism than Alzheimer's disease cases, who had more parietal and lateral/inferior temporal hypometabolism. Again, the ratio between temporal regions of interest differed significantly between groups. Two of the tau-negative patients, both of whom had an elevated inferior/medial temporal ratio, came to autopsy during the study and were found to have hippocampal sclerosis. Our finding that tau-negative amnestic mild cognitive impairment and dementia is associated with focal medial temporal and posterior cingulate hypometabolism extends prior reports in amyloid-negative cases. The inferior/medial temporal metabolism ratio can help identify tau-negative cases of amnestic dementia and may serve as a biomarker for hippocampal sclerosis.

Project description:Posterior cortical atrophy (PCA), usually an atypical clinical syndrome of Alzheimer's disease, has well-characterized patterns of cortical atrophy and tau deposition that are distinct from typical amnestic presentations of Alzheimer's disease. However, the mechanisms underlying the cortical spread of tau in PCA remain unclear. Here, in a sample of 17 biomarker-confirmed (A+/T+/N+) individuals with PCA, we sought to identify functional networks with heightened vulnerability to tau pathology by examining the cortical distribution of elevated tau as measured by 18F-flortaucipir (FTP) PET. We then assessed the relationship between network-specific FTP uptake and visuospatial cognitive task performance. As predicted, we found consistent and prominent localization of tau pathology in the dorsal attention network and visual network of the cerebral cortex. Elevated FTP uptake within the dorsal attention network (particularly the ratio of FTP uptake between the anterior and posterior nodes) was associated with poorer visuospatial attention in PCA; associations were also identified in other functional networks, although to a weaker degree. Furthermore, using functional MRI data collected from each patient at wakeful rest, we found that a greater anterior-to-posterior ratio in FTP uptake was associated with stronger intrinsic functional connectivity between anterior and posterior nodes of the dorsal attention network. Taken together, we conclude that our cross-sectional marker of anterior-to-posterior FTP ratio could indicate tau propagation from posterior to anterior dorsal attention network nodes, and that this anterior progression occurs in relation to intrinsic functional connectivity within this network critical for visuospatial attention. Our findings help to clarify the spatiotemporal pattern of tau propagation in relation to visuospatial cognitive decline and highlight the key role of the dorsal attention network in the disease progression of PCA.

Dataset Information

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

Publications

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets