TY - JOUR
T1 - Frontotemporal Dementia
T2 - Correlations Between Psychiatric Symptoms and Pathology
AU - Netherlands Brain Bank
AU - Scarioni, Marta
AU - Gami-Patel, Priya
AU - Timar, Yannick
AU - Seelaar, Harro
AU - van Swieten, John C.
AU - Rozemuller, Annemieke J.M.
AU - Dols, Annemiek
AU - Scarpini, Elio
AU - Galimberti, Daniela
AU - Hoozemans, Jeroen J.M.
AU - Pijnenburg, Yolande A.L.
AU - Dijkstra, Anke A.
N1 - Funding Information: We would like to thank Betty Tijms for statistical assistance. Financial support: The European Academy of Neurology supported this work with a research fellowship granted to M. Scarioni. This study was supported by a grant from the Memorabel ZonMW (733050507). Publisher Copyright: © 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Objective: The pathology of frontotemporal dementia, termed frontotemporal lobar degeneration (FTLD), is characterized by distinct molecular classes of aggregated proteins, the most common being TAR DNA-binding protein-43 (TDP-43), tau, and fused in sarcoma (FUS). With a few exceptions, it is currently not possible to predict the underlying pathology based on the clinical syndrome. In this study, we set out to investigate the relationship between pathological and clinical presentation at single symptom level, including neuropsychiatric features. Methods: The presence or absence of symptoms from the current clinical guidelines, together with neuropsychiatric features, such as hallucinations and delusions, were scored and compared across pathological groups in a cohort of 150 brain donors. Results: Our cohort consisted of 68.6% FTLD donors (35.3% TDP-43, 28% tau, and 5.3% FUS) and 31.3% non-FTLD donors with a clinical diagnosis of frontotemporal dementia and a different pathological substrate, such as Alzheimer's disease (23%). The presence of hyperorality points to FTLD rather than non-FTLD pathology (p < 0.001). Within the FTLD group, hallucinations in the initial years of the disease were related to TDP-43 pathology (p = 0.02), including but not limited to chromosome 9 open reading frame 72 (C9orf72) repeat expansion carriers. The presence of perseverative or compulsive behavior was more common in the TDP-B and TDP-C histotypes (p = 0.002). Interpretation: Our findings indicate that neuropsychiatric features are common in FTLD and form an important indicator of underlying pathology. In order to allow better inclusion of patients in targeted molecular trials, the routine evaluation of patients with frontotemporal dementia should include the presence and nature of neuropsychiatric symptoms. ANN NEUROL 2020.
AB - Objective: The pathology of frontotemporal dementia, termed frontotemporal lobar degeneration (FTLD), is characterized by distinct molecular classes of aggregated proteins, the most common being TAR DNA-binding protein-43 (TDP-43), tau, and fused in sarcoma (FUS). With a few exceptions, it is currently not possible to predict the underlying pathology based on the clinical syndrome. In this study, we set out to investigate the relationship between pathological and clinical presentation at single symptom level, including neuropsychiatric features. Methods: The presence or absence of symptoms from the current clinical guidelines, together with neuropsychiatric features, such as hallucinations and delusions, were scored and compared across pathological groups in a cohort of 150 brain donors. Results: Our cohort consisted of 68.6% FTLD donors (35.3% TDP-43, 28% tau, and 5.3% FUS) and 31.3% non-FTLD donors with a clinical diagnosis of frontotemporal dementia and a different pathological substrate, such as Alzheimer's disease (23%). The presence of hyperorality points to FTLD rather than non-FTLD pathology (p < 0.001). Within the FTLD group, hallucinations in the initial years of the disease were related to TDP-43 pathology (p = 0.02), including but not limited to chromosome 9 open reading frame 72 (C9orf72) repeat expansion carriers. The presence of perseverative or compulsive behavior was more common in the TDP-B and TDP-C histotypes (p = 0.002). Interpretation: Our findings indicate that neuropsychiatric features are common in FTLD and form an important indicator of underlying pathology. In order to allow better inclusion of patients in targeted molecular trials, the routine evaluation of patients with frontotemporal dementia should include the presence and nature of neuropsychiatric symptoms. ANN NEUROL 2020.
UR - http://www.scopus.com/inward/record.url?scp=85084081256&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ana.25739
DO - https://doi.org/10.1002/ana.25739
M3 - Article
C2 - 32281118
SN - 0364-5134
VL - 87
SP - 950
EP - 961
JO - Annals of neurology
JF - Annals of neurology
IS - 6
ER -