Proposed research criteria for prodromal behavioural variant frontotemporal dementia

Abstract

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed ‘mild behavioural and/or cognitive impairment in bvFTD’ (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer’s disease, and the false positive rate of diagnosis was 11–16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

A predictive coding framework of allostatic–interoceptive overload in frontotemporal dementia

“…If our model proves to be useful, preventive diagnosis and early characterization is possible through the use of the battery of tests formerly outlined. This battery will generate a physiological profile quantifying the multimodal risk of bvFTD symptomatology during prodromal stages [110]. This model can be also tested on longitudinal studies.…”

Towards Defining the Neuroanatomical Basis of Late-Onset Psychiatric Symptoms

“…As primary examples, evidence suggests that in patients with genetic Huntington's disease and bvFTD, psychiatric changes are usually the earliest symptoms, preceding motor and cognitive symptoms by 3 to 7 years. 8,16,44 The development of in vivo biomarkers for amyloid and tau has facilitated explorations of early and prodromal psychiatric symptoms of sporadic neurodegenerative disorders. In older individuals with normal cognition but amyloid positivity on PET imaging (i.e., high risk of developing dementia due to AD), the presence of anxiety significantly predicts future memory loss.…”

Behavioral Variant Frontotemporal Dementia

“…Based on a large cohort of asymptomatic and symptomatic members of kindreds with f-FTLD, the ALLFTD Consortium recently proposed a set of criteria for prodromal bvFTD in which the term mild behavioral and/or cognitive impairment in bvFTD (MBCI-FTD) was characterized 67 . The proposed MBCI-FTD criteria correctly classified 74% to 95% of two groups of prodromal f-FTLD mutation carriers, with a false-positive rate of less than 10% in healthy controls and 11% to 16% of individuals with prodromal AD 67 . Future research will need to refine the sensitivity and specificity of these criteria.…”