Frontotemporal Dementia: Correlations Between Psychiatric Symptoms and Pathology

Marta Scarioni, Priya Gami-Patel, Yannick Timar, Harro Seelaar, John C. van Swieten, Annemieke J.M. Rozemuller, Annemiek Dols, Elio Scarpini, Daniela Galimberti, Jeroen J.M. Hoozemans, Yolande A.L. Pijnenburg, Anke A. Dijkstra*, Netherlands Brain Bank

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Number of pages12
JournalAnnals of Neurology
Volume87
Issue number6
DOIs
Publication statusAccepted/In press - 1 Jan 2020

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