Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease

Kathryn Gauthreaux; Charles Mock; Merilee A. Teylan; Jessica E. Culhane; Yen Chi Chen; Kwun C.G. Chan; Yuriko Katsumata; Peter T. Nelson; Walter A. Kukull

doi:10.1093/jnen/nlac093

Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease

Kathryn Gauthreaux, Charles Mock, Merilee A. Teylan, Jessica E. Culhane, Yen Chi Chen, Kwun C.G. Chan, Yuriko Katsumata, Peter T. Nelson, Walter A. Kukull

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer's Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.

Original language	English
Pages (from-to)	975-987
Number of pages	13
Journal	Journal of Neuropathology and Experimental Neurology
Volume	81
Issue number	12
DOIs	https://doi.org/10.1093/jnen/nlac093
State	Published - Dec 1 2022

Bibliographical note

Funding Information:
PTN is supported by NIA/NIH grants R01 AG061111, RF1 NS118584. YK is supported by NIA/NIH grants R56AG057191, R01AG057187, R21AG061551, R01AG054060, and the UK-ADC P30AG028383 from the National Institute on Aging. The NACC database is funded by NIA/NIH grant U24 AG072122. NACC data are contributed by the NIA-funded ADCs: P50 AG005131 (PI James Brewer, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG005138 (PI Mary Sano, PhD), P50 AG005142 (PI Helena Chui, MD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005681 (PI John Morris, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG008051 (PI Thomas Wisniewski, MD), P50 AG008702 (PI Scott Small, MD), P30 AG010124 (PI John Trojanowski, MD, PhD), P30 AG010129 (PI Charles DeCarli, MD), P30 AG010133 (PI Andrew Saykin, PsyD), P30 AG010161 (PI David Bennett, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG013854 (PI Robert Vassar, PhD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P30 AG019610 (PI Eric Reiman, MD), P50 AG023501 (PI Bruce Miller, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG028383 (PI Linda Van Eldik, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P30 AG035982 (PI Russell Swerdlow, MD), P50 AG047266 (PI Todd Golde, MD, PhD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG049638 (PI Suzanne Craft, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Marwan Sabbagh, MD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), and P30 AG072959 (PI James Leverenz, MD).

Publisher Copyright:
© 2022 The Author(s).

Keywords

Alzheimer disease
Depression
Lewy body
Limbic predominant age-related TDP-43 encephalopathy
Neuropsychiatric
TDP-43

ASJC Scopus subject areas

Medicine (all)

Access to Document

10.1093/jnen/nlac093

Cite this

Gauthreaux, K., Mock, C., Teylan, M. A., Culhane, J. E., Chen, Y. C., Chan, K. C. G., Katsumata, Y., Nelson, P. T., & Kukull, W. A. (2022). Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease. Journal of Neuropathology and Experimental Neurology, 81(12), 975-987. https://doi.org/10.1093/jnen/nlac093

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title = "Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease",

abstract = "Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer's Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.",

keywords = "Alzheimer disease, Depression, Lewy body, Limbic predominant age-related TDP-43 encephalopathy, Neuropsychiatric, TDP-43",

author = "Kathryn Gauthreaux and Charles Mock and Teylan, {Merilee A.} and Culhane, {Jessica E.} and Chen, {Yen Chi} and Chan, {Kwun C.G.} and Yuriko Katsumata and Nelson, {Peter T.} and Kukull, {Walter A.}",

note = "Funding Information: PTN is supported by NIA/NIH grants R01 AG061111, RF1 NS118584. YK is supported by NIA/NIH grants R56AG057191, R01AG057187, R21AG061551, R01AG054060, and the UK-ADC P30AG028383 from the National Institute on Aging. The NACC database is funded by NIA/NIH grant U24 AG072122. NACC data are contributed by the NIA-funded ADCs: P50 AG005131 (PI James Brewer, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG005138 (PI Mary Sano, PhD), P50 AG005142 (PI Helena Chui, MD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005681 (PI John Morris, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG008051 (PI Thomas Wisniewski, MD), P50 AG008702 (PI Scott Small, MD), P30 AG010124 (PI John Trojanowski, MD, PhD), P30 AG010129 (PI Charles DeCarli, MD), P30 AG010133 (PI Andrew Saykin, PsyD), P30 AG010161 (PI David Bennett, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG013854 (PI Robert Vassar, PhD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P30 AG019610 (PI Eric Reiman, MD), P50 AG023501 (PI Bruce Miller, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG028383 (PI Linda Van Eldik, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P30 AG035982 (PI Russell Swerdlow, MD), P50 AG047266 (PI Todd Golde, MD, PhD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG049638 (PI Suzanne Craft, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Marwan Sabbagh, MD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), and P30 AG072959 (PI James Leverenz, MD). Publisher Copyright: {\textcopyright} 2022 The Author(s).",

year = "2022",

month = dec,

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doi = "10.1093/jnen/nlac093",

language = "English",

volume = "81",

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Gauthreaux, K, Mock, C, Teylan, MA, Culhane, JE, Chen, YC, Chan, KCG, Katsumata, Y , Nelson, PT & Kukull, WA 2022, 'Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease', Journal of Neuropathology and Experimental Neurology, vol. 81, no. 12, pp. 975-987. https://doi.org/10.1093/jnen/nlac093

Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease. / Gauthreaux, Kathryn; Mock, Charles; Teylan, Merilee A. et al.
In: Journal of Neuropathology and Experimental Neurology, Vol. 81, No. 12, 01.12.2022, p. 975-987.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease

AU - Gauthreaux, Kathryn

AU - Mock, Charles

AU - Teylan, Merilee A.

AU - Culhane, Jessica E.

AU - Chen, Yen Chi

AU - Chan, Kwun C.G.

AU - Katsumata, Yuriko

AU - Nelson, Peter T.

AU - Kukull, Walter A.

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Y1 - 2022/12/1

N2 - Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer's Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.

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KW - Depression

KW - Lewy body

KW - Limbic predominant age-related TDP-43 encephalopathy

KW - Neuropsychiatric

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Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease

Abstract

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