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.
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/12/1
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.
AB - 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.
KW - Alzheimer disease
KW - Depression
KW - Lewy body
KW - Limbic predominant age-related TDP-43 encephalopathy
KW - Neuropsychiatric
KW - TDP-43
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U2 - 10.1093/jnen/nlac093
DO - 10.1093/jnen/nlac093
M3 - Article
C2 - 36264254
AN - SCOPUS:85142403144
SN - 0022-3069
VL - 81
SP - 975
EP - 987
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 12
ER -