Differences in sex distribution between genetic and sporadic FTD

AbstractBackgroundThe reported sex distribution differs between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that have resulted in variable findings. Our aim was to determine the sex distribution in a large international retrospective cohort of sporadic and genetic FTD.MethodWe included patients with probable and definite behavioural variant frontotemporal dementia (bvFTD), non‐fluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA) and right temporal variant frontotemporal dementia (rtvFTD) from the Amsterdam Dementia Cohort, the Montreal Neurological Institute Cohort, the University of Ulm and Technical University of Munich Cohort (part of the German Consortium of Frontotemporal Lobal Degeneration), the Policlinico Milan Cohort and the Sydney FRONTIER Cohort. We compared sex distribution between genetic and sporadic FTD using χ2 tests.ResultA total of 910 subjects were included (56.3% male), of whom 654 had bvFTD, 99 nfvPPA, 117 svPPA and 40 rtvFTD. Of these, 215 had genetic FTD and the sex distribution was equal (51.2% male), which did not differ significantly from sporadic FTD (57.8% male, χ2 p=0.081). In the sporadic bvFTD subgroup, we found a male predominance (61.6% males compared to 52.9% males in the bvFTD genetic group, χ 2 p=0.04). No sex distribution differences between sporadic and genetic cases were found in the other clinical FTD subgroups (all p>0.05).ConclusionDifferences in sex distribution between genetic and sporadic behavioural variant of FTD may provide important clues for its differential pathogenesis and warrants further research

Diagnostic Instability Over Time in the Late-Onset Frontal Lobe Syndrome: When Can We Say it's FTD?

Objectives: Distinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We investigated diagnostic instability in a neuropsychiatric cohort up to 8 years after baseline visit and identified which clinical hallmarks contribute to diagnostic instability. Design: Diagnoses of participants of the late-onset frontal lobe (LOF) study were collected from the baseline visit (T0) and the 2-year follow-up visit (T2). Clinical outcomes were retrieved 5–8 years after baseline visit (Tfinal). Endpoint diagnoses were categorized into bvFTD, PPD and other neurological disorders (OND). We calculated the total amount of participants that switched diagnosis between T0-T2 and T2-Tfinal. Clinical records of participants that switched diagnosis were assessed. Results: Of the 137 patients that were included in the study, the final diagnoses at Tfinal were bvFTD 24.1% (n = 33), PPD 39.4% (n = 54), OND 33.6% (n = 46) and unknown 2.9% (n = 4). Between T0 and T2, a total of 29 (21.2%) patients switched diagnosis. Between T2 and Tfinal, 8 (5.8%) patients switched diagnosis. Prolonged follow-up identified few cases with diagnostic instability. Major contributors to diagnostic instability where a nonconverting diagnosis of possible bvFTD and a probable bvFTD diagnosis based on informant-based history and an abnormal FDG-PET scan whilst having a normal MRI. Conclusion: Considering these lessons, a FTD diagnosis remains stable enough to conclude that 2 years is sufficient to say if a patient with late-life behavioral disorder has FTD

A caregiver's perspective on clinically relevant symptoms in behavioural variant frontotemporal dementia: tools for disease management and trial design

Background: Adequate detection of symptoms and disease progression in behavioural variant frontotemporal dementia (bvFTD) is complex. Dementia cohorts usually utilize cognitive and functional measures, which fail to detect dominant behavioural and social cognitive deficits in bvFTD. Moreover, since patients typically have a loss of insight, caregivers are important informants. This is the first qualitative study to investigate caregiver relevant symptoms during the disease course of bvFTD, aiming to improve tools for diagnosis, progression, and future clinical trials. Methods: Informal caregivers of patients in different disease stages of bvFTD (N = 20) were recruited from the neurology outpatient clinic of the Amsterdam UMC and a patient organization for peer support in the Netherlands. Their perspectives on clinical relevance were thoroughly explored during individual semi-structured interviews. Inductive content analysis with open coding was performed by two researchers independently to establish overarching themes and patterns. Results: Caregivers reported a variety of symptoms, in which (i) loss of emotional connection, (ii) preoccupation and restlessness, and (iii) apathy and dependency compose major themes of relevance for diagnosis and treatment. Within heterogeneous disease trajectories, symptom presence differed between stages and among individuals, which is relevant in the context of progression and outcome measures. Significant socio-emotional changes dominated in early stages, while severe cognitive, behavioural, and physical deterioration shifted focus from predominant personality change to quality of life in later stages. Conclusions: Caregiver perspectives on target symptoms in bvFTD differ according to clinical stage and patient-caregiver characteristics, with significant socio-emotional changes characterizing early stages. These findings call for more appropriate tools and symptomatic treatments, as well as a personalized approach in treatment of bvFTD and a focus on early stage interventions in clinical trial design

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities–focused research

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice