Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study
Abstract Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the media...
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BMC
2021-08-01
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Series: | Acta Neuropathologica Communications |
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Online Access: | https://doi.org/10.1186/s40478-021-01233-3 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Megan A. Iida Kurt Farrell Jamie M. Walker Timothy E. Richardson Gabriel A. Marx Clare H. Bryce Dushyant Purohit Gai Ayalon Thomas G. Beach Eileen H. Bigio Etty P. Cortes Marla Gearing Vahram Haroutunian Corey T. McMillan Edward B. Lee Dennis W. Dickson Ann C. McKee Thor D. Stein John Q. Trojanowski Randall L. Woltjer Gabor G. Kovacs Julia K. Kofler Jeffrey Kaye Charles L. White John F. Crary |
spellingShingle |
Megan A. Iida Kurt Farrell Jamie M. Walker Timothy E. Richardson Gabriel A. Marx Clare H. Bryce Dushyant Purohit Gai Ayalon Thomas G. Beach Eileen H. Bigio Etty P. Cortes Marla Gearing Vahram Haroutunian Corey T. McMillan Edward B. Lee Dennis W. Dickson Ann C. McKee Thor D. Stein John Q. Trojanowski Randall L. Woltjer Gabor G. Kovacs Julia K. Kofler Jeffrey Kaye Charles L. White John F. Crary Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study Acta Neuropathologica Communications PART Dementia Aging Braak ARTAG |
author_facet |
Megan A. Iida Kurt Farrell Jamie M. Walker Timothy E. Richardson Gabriel A. Marx Clare H. Bryce Dushyant Purohit Gai Ayalon Thomas G. Beach Eileen H. Bigio Etty P. Cortes Marla Gearing Vahram Haroutunian Corey T. McMillan Edward B. Lee Dennis W. Dickson Ann C. McKee Thor D. Stein John Q. Trojanowski Randall L. Woltjer Gabor G. Kovacs Julia K. Kofler Jeffrey Kaye Charles L. White John F. Crary |
author_sort |
Megan A. Iida |
title |
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study |
title_short |
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study |
title_full |
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study |
title_fullStr |
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study |
title_full_unstemmed |
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study |
title_sort |
predictors of cognitive impairment in primary age-related tauopathy: an autopsy study |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2021-08-01 |
description |
Abstract Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n = 174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p = 0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p = 0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p < 0.0001), but other features including ARTAG (p = 0.03) and hippocampal atrophy (p = 0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function. |
topic |
PART Dementia Aging Braak ARTAG |
url |
https://doi.org/10.1186/s40478-021-01233-3 |
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doaj-34a4f4e1641746a88e977b7cf3b9dcc52021-08-08T11:10:33ZengBMCActa Neuropathologica Communications2051-59602021-08-019111210.1186/s40478-021-01233-3Predictors of cognitive impairment in primary age-related tauopathy: an autopsy studyMegan A. Iida0Kurt Farrell1Jamie M. Walker2Timothy E. Richardson3Gabriel A. Marx4Clare H. Bryce5Dushyant Purohit6Gai Ayalon7Thomas G. Beach8Eileen H. Bigio9Etty P. Cortes10Marla Gearing11Vahram Haroutunian12Corey T. McMillan13Edward B. Lee14Dennis W. Dickson15Ann C. McKee16Thor D. Stein17John Q. Trojanowski18Randall L. Woltjer19Gabor G. Kovacs20Julia K. Kofler21Jeffrey Kaye22Charles L. White23John F. Crary24Department of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREDepartment of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREDepartment of Pathology and Laboratory Medicine and The Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San AntonioDepartment of Pathology and Laboratory Medicine and The Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San AntonioDepartment of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREDepartment of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREDepartment of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREUltragenyx PharmaceuticalsBanner Sun Health Research InstituteDepartment of Pathology, Northwestern Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of MedicineDepartment of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREDepartment of Pathology and Laboratory Medicine, Emory University School of MedicineDepartments of Psychiatry and Neuroscience, Alzheimer’s Disease Research Center, Icahn School of Medicine At Mount SinaiDepartment of Neurology, Perelman School of Medicine, Penn FTD Center, Center for Neurodegenerative Disease Research, University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, Translational Neuropathology Research Laboratory, Perelman School of Medicine at the University of PennsylvaniaDepartment of Neuroscience, Mayo ClinicDepartment of Pathology, VA Medical Center & Boston University School of MedicineDepartment of Pathology, VA Medical Center & Boston University School of MedicineCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Pathology, Oregon Health Sciences UniversityLaboratory Medicine Program, Krembil Brain Institute University Health Network Toronto OntarioDepartment of Pathology, University of Pittsburgh Medical CenterDepartment of Neurology, Oregon Health & Science UniversityNeuropathology Laboratory, Department of Pathology, University of Texas Southwestern Medical CenterDepartment of Pathology, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, Friedman Brain Institute, Neuropathology Brain Bank & Research CoREAbstract Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n = 174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p = 0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p = 0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p < 0.0001), but other features including ARTAG (p = 0.03) and hippocampal atrophy (p = 0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.https://doi.org/10.1186/s40478-021-01233-3PARTDementiaAgingBraakARTAG |