{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:38:12Z","timestamp":1789486692548,"version":"build-2803163510"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21 AG078505"],"award-info":[{"award-number":["R21 AG078505"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020423","name":"Texas Alzheimer\u2019s Research and Care Consortium","doi-asserted-by":"crossref","award":["957581"],"award-info":[{"award-number":["957581"]}],"id":[{"id":"10.13039\/100020423","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020423","name":"Texas Alzheimer\u2019s Research and Care Consortium","doi-asserted-by":"crossref","award":["957607"],"award-info":[{"award-number":["957607"]}],"id":[{"id":"10.13039\/100020423","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary age-related tauopathy (PART) is a \u03b2-amyloid-independent tauopathy, thought by some to be a distinct process from Alzheimer disease neuropathologic change (ADNC). Two categories of PART have been defined: definite PART (those with complete absence of \u03b2-amyloid deposition) and possible PART (those with minimal and restricted \u03b2-amyloid distribution). It is unclear whether there is any significant cognitive effect of \u201cisolated\u201d or \u201cpure\u201d PART, as opposed to ADNC, in which cognitive decline mirrors pathologic progression. We evaluated the effects of neurodegenerative pathologies on longitudinal cognitive decline using a combination of univariate analysis, multivariable logistic regression analysis, and variance decomposition in patient cohorts with neuropathologically confirmed definite PART (n\u2009=\u2009174) and possible PART (n\u2009=\u2009182). ADNC-related pathologies did not significantly contribute to cognitive impairment in either cohort. Cognitive decline in definite PART was instead dependent on the presence and severity of TDP-43 pathology\/limbic-predominant age-related TDP-43 encephalopathy (LATE) stage, Lewy body pathology, and arteriolosclerosis, while cognitive impairment in possible PART was primarily affected by hippocampal sclerosis and infarcts. Additionally, 67.8%-75.7% of variance in cognitive decline was unaccounted for by these neurodegenerative pathologies. These results indicate that PART pathology in isolation does not significantly impair cognition, which is instead primarily influenced by comorbid neuropathologic features.<\/jats:p>","DOI":"10.1093\/jnen\/nlag053","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:27:02Z","timestamp":1777724822000},"page":"951-962","source":"Crossref","is-referenced-by-count":0,"title":["Comorbid neuropathologies but not Braak stage influence cognitive impairment in primary age-related tauopathy"],"prefix":"10.1093","volume":"85","author":[{"given":"Shrishtee","family":"Kandoi","sequence":"first","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Hiya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Maldonado-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K","family":"Rohde","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Department of Pathology, Amsterdam UMC NL , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Bernardes","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho , Braga,","place":["Portugal"]},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory , Braga,","place":["Portugal"]},{"name":"Department of Neuroradiology, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco C","family":"Almeida","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho , Braga,","place":["Portugal"]},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory , Braga,","place":["Portugal"]},{"name":"Department of Neuroradiology, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Samanamud","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Clare","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Christian","family":"Virata","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyanne C","family":"Slocum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ema","family":"Mir","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Charles L","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center , Dallas, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V","family":"Daoud","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center , Dallas, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Crary","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago Gil","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho , Braga,","place":["Portugal"]},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory , Braga,","place":["Portugal"]},{"name":"Department of Neuroradiology, Hospital de Braga, ULS Braga, Sete Fontes\u2014S\u00e3o Victor , Braga,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitzi M","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cedars Sinai Medical Center , Los Angeles, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-5517","authenticated-orcid":false,"given":"Timothy E","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"2026091509123268200_nlag053-B1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/BF00296494","article-title":"Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects","volume":"88","author":"Bancher","year":"1994","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1046\/j.1440-1789.2003.00522.x","article-title":"Senile dementia of the neurofibrillary tangle type (tangle-only dementia): neuropathological criteria and clinical guidelines for diagnosis","volume":"23","author":"Yamada","year":"2003","journal-title":"Neuropathology"},{"key":"2026091509123268200_nlag053-B3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00401-006-0156-7","article-title":"Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease","volume":"113","author":"Jellinger","year":"2007","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B4","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00401-014-1349-0","article-title":"Primary age-related tauopathy (PART): a common pathology associated with human aging","volume":"128","author":"Crary","year":"2014","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","article-title":"National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease","volume":"8","author":"Hyman","year":"2012","journal-title":"Alzheimers Dement"},{"key":"2026091509123268200_nlag053-B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach","volume":"123","author":"Montine","year":"2012","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B7","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00401-014-1356-1","article-title":"Are cases with tau pathology occurring in the absence of Abeta deposits part of the AD-related pathological process?","volume":"128","author":"Braak","year":"2014","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B8","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00401-015-1390-7","article-title":"PART is part of Alzheimer disease","volume":"129","author":"Duyckaerts","year":"2015","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B9","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00401-015-1407-2","article-title":"PART, a distinct tauopathy, different from classical sporadic Alzheimer disease","volume":"129","author":"Jellinger","year":"2015","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00401-025-02921-3","article-title":"Reply: PART and amyloid cascade hypotheses are alive and well (but are not so simple)","volume":"150","author":"Braak","year":"2025","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s00401-025-02920-4","article-title":"PART and amyloid cascade hypotheses are alive and well (but are not so simple). Scientific commentary on: \u201cSequence and trajectory of early Alzheimer\u2019s disease-related tau inclusions in the hippocampal formation of cases without amyloid-beta deposits\u201d","volume":"150","author":"Nelson","year":"2025","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00401-025-02943-x","article-title":"Primary age-related tauopathy","volume":"150","author":"Richardson","year":"2025","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"key":"2026091509123268200_nlag053-B14","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-12679-1","volume-title":"Neuroanatomy and Pathology of Sporadic Alzheimer\u2019s 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