Accurate Assessment of Behavioral Variant Frontotemporal Dementia

Abstract

Behavioral variant Frontotemporal dementia (bvFTD) is a neurodegenerative syndrome characterized by profound changes in personality and behavior, including social disinhibition, loss of empathy, apathy and compulsive behaviors. While cognitive decline does occur (typically beginning with executive dysfunction), these issues tend to emerge mid-disease course, rather than early on. Onset is insidious, typically beginning between ages 45-65 and prevalence is equal to Alzheimer's disease (AD) in individuals under the age of 65. Despite signifi cant advancements in our understanding of bvFTD over the past 12 years, misdiagnosis remains common. For example, a signifi cant subset of individuals with bvFTD initially receive a diagnosis of early-onset AD, or late life psychiatric disturbance. Given their expertise in the assessment of cognition, behavior and emotion, neuropsychologists can play an important role in the differential diagnosis and management of this disease. This chapter begins with an up-to-date discussion of the clinical, neuropathological and genetic features of the disease, and then moves into a review of the neuropsychological literature. A structured discussion of key aspects to cover in a neuropsychological assessment is provided, and a case example of a 'typical' bvFTD patient is presented. Behavioral variant frontotemporal dementia (bvFTD) is one of three neurodegenerative syndromes that are collectively referred to as frontotemporal dementia (FTD). Initially thought to be rare, we now know that it is equally as common as Alzheimer's disease in individuals under the age of 65 [ 1 ] and is the third most common dementia after Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) [ 2 ] . While estimates of the prevalence of FTD vary, population-based studies in both the United States and United Kingdom estimate a sporadic occurrence at around 3.3-3.5/100,000 in individuals between 45 and 65 years of age [ 3,4 ] . Age of onset is typically in the presenium, though onset ranges considerably from the 30s to 90s [ 1,5,6 ] . The usual duration of FTD ranges from 8 to 11 years [ 7 ] .Clinically, FTD is expressed as three main variants [ 8 ] . BvFTD is characterized by profound and early changes in personality and behavior [ 8 ] . This phenotype is most common and accounts for approximately 70% of the clinical expression of the disease [ 9 ] . As such, bvFTD will be the focus of this chapter. The other two variants are primary progressive aphasic syndromes. The semantic variant (svPPA) is associated with the loss of word knowledge (e.g., semantic structure of language), while the non fl uent variant (nfPPA) is characterized by early disturbances in motor speech output and loss of syntax (e.g., grammatical structure of language) [ 8,10 ] . These two variants account for approximately 15% and 10% of the phenotypic expression of the disease, respectively [ 9 ] . Gender distribution tends to vary by clinical syndrome. Many studies fi nd a male bias in bvFTD and svPPA and a female bias in nfPPA [ ...

A Meta-Analysis of Neuropsychological Functioning in the Logopenic Variant of Primary Progressive Aphasia: Comparison with the Semantic and Non-Fluent Variants

“…Measures of social cognition have received widespread attention in frontotemporal lobar degeneration (FTLD), as these measures are thought to be sensitive to the early deterioration in social comportment and behavior observed in svPPA and the behavioral variant of FTD (bvFTD; Bora, Velakoulis, & Walterfang, 2016;Bora, Walterfang, & Velakoulis, 2015). Social cognitive deficits are more characteristic of bvFTD than AD (Bora et al, 2016;LaMarre & Kramer, 2013), possibly reflecting neurodegeneration of anterior and ventral aspects of the prefrontal cortex affected early in the course of bvFTD but relatively spared in early-stage lvPPA. The limited number of studies in lvPPA precluded interpretation of social cognitive findings relative to svPPA and nfvPPA and emphasizes the need for further work in this area.…”

A meta-analysis of neuropsychological, social cognitive, and olfactory functioning in the behavioral and language variants of frontotemporal dementia

“…Though executive deficits are present in bvFTD, they are not consistently so and many patients can produce entirely normal scores on traditional tests of executive functioning years into the illness (LaMarre and Kramer, 2013). These inconsistent findings have been attributed to multiple factors, including the heterogeneity of the executive functioning construct, variable patterns of frontal degeneration, individual differences in cognitive reserve, and missing data due to a behavioral disturbance in bvFTD patients (LaMarre and Kramer, 2013; Smeding and de Koning, 2000). In the current study, the degree of executive deficits in bvFTD was similar in magnitude to that of processing speed, memory, olfaction, IQ, social cognition, and ideational fluency.…”

“…Though the anatomical, molecular, genetic, and neurochemical aspects of FTD are increasingly understood in relation to its clinical phenotypes, neuropsychological correlates of pathological substrates have proven to be inconsistent and at times counterintuitive (LaMarre and Kramer, 2013; Sitek et al ., 2015). The variability in FTD neuropsychological profiles has been attributed to multiple factors – low sample size, phenotypically mixed cohorts, differing diagnostic criteria, and the absence of disease staging information (Harciarek and Cosentino, 2013; LaMarre and Kramer, 2013). Despite the difficulties in characterizing cognition in bvFTD, it is generally accepted that its early cognitive manifestations result in gradual changes in executive functioning where visuospatial skills are preserved until later in the course (Ng et al ., 2015).…”

“…The clinical presentation of FTD encompasses three primary conditions, a behavioral variant, and two language variants – non-fluent (nfvPPA) and semantic (svPPA) primary progressive aphasia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by early and prominent change in comportment, personality, and social functioning (Rascovsky et al ., 2011; LaMarre and Kramer, 2013), whereas nfvPPA and svPPA are defined by progressive decline in speech production or semantic knowledge (Gorno-Tempini et al ., 2011; Mesulam et al ., 2014). Early and accurate differentiation has strong implications for the pathological basis of each syndrome and is critical for guiding treatment and for clinical trial recruitment – which will increasingly rely on etiopathologic predictions (Woolley et al ., 2011).…”

Ethical practice in forensic neuropsychology.

“…Some disorders can be particularly difficult to detect or accurately diagnose, particularly in the early stages or mild forms. Pick disease is one such condition, particularly early in the disease process when the presenting symptoms often involve behavior change and cognition remains intact, although overlap with Alzheimer's disease is often evident as the disease progresses (LaMarre & Kramer, 2013;Lezak, Howieson, & Loring, 2004;Wittenberg et al, 2008).…”