Giannini, L.A.A. (Lucia) (2017) Divergent patterns of frontotemporal lobar degeneration in primary progressive aphasia. thesis, Medicine.
Full text available on request.Abstract
Background/Aim: Primary progressive aphasia (PPA) with underlying frontotemporal lobar degeneration (FTLD) can be caused by pathological inclusions of the tau protein or of the transactive response DNA-binding protein 43 (TDP-43). To improve understanding of clinical correlates of FTLD in PPA, we aimed to compare hemispheric and regional distribution of pathology in FTLD-Tau and FTLD-TDP. Methods: We performed a retrospective study of a well-characterized autopsy cohort of FTLD-PPA patients (n = 27). We measured density of pathology using a validated method of digital image analysis in multiple brain regions. We analyzed laterality, white matter (WM)-to-grey matter (GM) burden and regional distribution of pathology. Additionally, we analyzed ante-mortem MRI cortical thickness in region of interests matching autopsy-sampled regions in a subset of patients. Results: Density of pathology was lateralized to the left hemisphere in both FTLD-TDP and FTLD-Tau, consistent with clinical PPA. FTLD-Tau had higher relative WM burden than FTLD-TDP. Within-group regional analyses found areas of peak pathology (i.e. highest density of pathology among five analyzed core regions), in left mid-laterofrontal cortex (MFC) in FTLD-Tau and left orbitofrontal cortex (OFC) in FTLD-TDP. In direct between-group comparisons, FTLD-TDP had greater pathology in left OFC, while FTLD-Tau had more in left MFC. We found clinicopathological associations of left MFC pathology with nonfluent speech and of left OFC with single-word comprehension impairment across the whole cohort. Post-mortem density of pathology in GM was associated with ante-mortem loss of cortical thickness on MRI, and relatively high atrophy was found in regions of peak pathology. Interpretation: Pathology in PPA is left lateralized at end stage disease, and disparate FTLD-TDP and FTLD-Tau pathologies associated with clinical PPA acquire divergent patterns of pathology distribution, which are consistent with ante-mortem clinical features and MRI atrophy. These findings suggest that distinctive tissue-patterns of molecular pathology underlying PPA may be detected during life.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and de Jong, Dr. Bauke M. and Department of Neurology, University of Groningen |
| Supervisor name: | Daily supervisor: and Irwin, Dr. David J. and Penn Frontotemporal Degeneration Center, University of Penns |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:46 |
| Last Modified: | 25 Jun 2020 10:46 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/780 |
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