Frontotemporal Dementia: Correlations Between Psychiatric Symptoms and Pathology

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.

Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: findings from a population-based study

“…33 Furthermore, dementias and other types of brain disorders causing behavioral symptoms are grouped within psychiatric disorders in ICD-10; 24 these show high degrees of symptom overlap with neurodegenerative disorders, especially regarding mood and cognitive functioning. 34,35 Therefore, people with neurological conditions, either comorbid with psychiatric conditions or presenting symptomatology overlapping with psychiatric symptoms, being both within the realm of brain functioning, would be expected to be affected similarly in the context of COVID-19.…”

“…33 Furthermore, dementias and other types of brain disorders causing behavioral symptoms are grouped within psychiatric disorders in ICD-10; 24 these show high degrees of symptom overlap with van der Meer et al neurodegenerative disorders, especially regarding mood and cognitive functioning. 34,35 Therefore, people with neurological conditions, either comorbid with psychiatric conditions or presenting symptomatology overlapping with psychiatric symptoms, being both within the realm of brain functioning, would be expected to be affected similarly in the context of COVID-19. Furthermore, when looking at the symptom level in the UK Biobank sample (mental health questionnaire items), no relationship was found between testing likelihood or outcome and continuous measures of depressive, manic, anxiety, addiction, psychotic experiences, self-harm or happiness items in those without a past or current diagnosis of psychiatric disorder.…”

Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia

“…32 C9orf72 and GRN carriers showed fewer differences in frequencies and trajectories of behavioral and neuropsychiatric symptoms between them when compared with MAPT carriers, possibly owing to their common underlying TAR DNA-binding protein 43 (TDP-43) proteinopathy, as opposed to tau pathology. 35 Parallels between C9orf72 and GRN carriers have also recently emerged regarding early cognitive symptoms, 31 serum neurofilament light measures, 36 and age at symptom onset and death, 37 compared with MAPT carriers. This similarity could have crucial implications, because the direct comparison of symptoms among gene variant groups may be important in the consideration of basket-design clinical trials where, for example, patients with TDP-43 pathology arising from different gene variants (C9orf72 and GRN) may be grouped together.…”

The bvFTD phenocopy syndrome: a case study supported by repeated MRI, [18F]FDG-PET and pathological assessment

“…Yet, a diagnosis of bvFTD was initially made on prevailing clinical criteria (Neary et al, 1998), whereas nowadays frontotemporal abnormalities on neuroimaging are required to meet the criteria of probable bvFTD (Rascovsky et al, 2011). The diagnostic accuracy of bvFTD has clearly increased over the last decade with the application of the revised diagnostic criteria (Scarioni et al, 2020). In a group of patients presenting with late-onset behavioral change, the specificity of the consensus criteria for possible bvFTD was only 27%, whereas adding the neuroimaging criterion increased specificity to 82% .…”