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The neuropathological entity of frontotemporal lobar degeneration with abnormal precipitates of the transactive response DNA binding protein TDP-43 (FTLD-TDP) of type C (TDP-C) is one of the most distinctive examples. TDP-C invariably starts with neurodegeneration (atrophy) confined to the temporopolar regions. The process is usually asymmetric, causing behavioural abnormalities and associative agnosia when predominantly right-sided, semantic primary progressive aphasia when left-sided, and semantic dementia when bilateral.<\/jats:p>\n                  <jats:p>In this study, we investigated the relationship between progression of atrophy and the progressive dissolution of word comprehension in TDP-C patients with asymmetric left temporopolar region degeneration. For the sake of homogeneity and in order to use a common yardstick of functional progression, we focused on patients with leftward asymmetry and initially isolated verbal impairment. Using data from 24 visits with structural MRI scans and specialized tests of naming, word definition and word-to-picture matching, we stratified the anatomy of peak degeneration sites according to three increasingly advanced stages of impaired noun representations. According to this pattern of progression, an initial stage of relatively isolated anomia is followed by additional intra-category blurring of word meaning and, at still more advanced stages, inter-category blurring. Voxel-based morphometry maps of grey matter volume were binarized to identify regions most frequently atrophied at each of these stages.<\/jats:p>\n                  <jats:p>The results illustrate that the progressive dissolution of word meaning is associated with caudal progression of atrophy from the left temporopolar cortex at initial stages to more posterior fusiform, lateral temporal and temporo-occipital regions in later stages. The stratification of progressive atrophy by precisely characterized stages of word comprehension impairment, rather than by estimated time of symptom onset, offers a functional rather than only chronological anatomy of progression for TDP-C and a clearer view of the relationship between temporopolar region components and the cognitive mapping of word representations.<\/jats:p>","DOI":"10.1093\/brain\/awaf369","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T12:13:23Z","timestamp":1759320803000},"page":"1194-1207","source":"Crossref","is-referenced-by-count":5,"title":["Atrophy progression in frontotemporal lobar degeneration-TDP-C with primary progressive aphasia"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-846X","authenticated-orcid":false,"given":"Elena","family":"Barbieri","sequence":"first","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-5350","authenticated-orcid":false,"given":"Allegra S","family":"Kawles","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Los","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Behn","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changiz","family":"Geula","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gefen","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2605-5205","authenticated-orcid":false,"given":"Sandra","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5731-851X","authenticated-orcid":false,"given":"Marek-Marsel","family":"Mesulam","sequence":"additional","affiliation":[{"name":"Mesulam Institute for Cognitive Neurology and Alzheimer\u2019s Disease, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neurology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"2026040804051659300_awaf369-B1","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41586-024-08024-5","article-title":"Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP type 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