Abstract

It is a common pathway for patients with the behavioral variant of frontotemporal dementia (bvFTD) to be first misdiagnosed with a primary psychiatric disorder, a considerable proportion of them being diagnosed with bipolar disorder (BD). Conversely, not rarely patients presenting in late life with a first episode of mania or atypically severe depression are initially considered to have dementia before the diagnosis of late-onset BD is reached. Beyond some shared features that make these conditions particularly prone to confusion, especially in the elderly, the relationship between bvFTD and BD is far from simple. Patients with BD often have cognitive complaints as part of their psychiatric disorder but are at an increased risk of developing dementia, including FTD. Likewise, apathy and disinhibition, common features of depression and mania, respectively, are among the core features of the bvFTD syndrome, not to mention that depression may coexist with dementia. In this article, we take advantage of the current knowledge on the neurobiology of these two nosologic entities to review their historical and conceptual interplay, highlighting the clinical, genetic and neuroimaging features that may be shared by both disorders or unique to each of them.

Highlights

  • Frontotemporal dementia (FTD) is a severe neurodegenerative disorder associated with aging and several behavioral and cognitive symptoms, with an overall prevalence estimated in 15–22/100,000 [1]

  • Our review’s guiding question was: “Which shared and distinct neuropathological and genetical findings may be identified between behavioral variant of frontotemporal dementia (bvFTD) and bipolar disorder (BD) and how these biological markers associate with the clinical presentation in each of the disorders?” The inclusion criteria were articles in any language since they were available in the electronic databases [(Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane, and SCOPUS)]

  • gamma-aminobutyric acid (GABA) hypofunction would result from glutamatergic hyperactivity due to the excessive activation of N-methyl-D-aspartate receptor (NMDA-R) [88]; in one study, the enhanced response to NMDA-R medications has corroborated such a hypothesis compared to refractiveness to lorazepam among subjects with catatonia [77]

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Summary

Introduction

Frontotemporal dementia (FTD) is a severe neurodegenerative disorder associated with aging and several behavioral and cognitive symptoms, with an overall prevalence estimated in 15–22/100,000 [1]. Bipolar disorder (BD) is a highly disabling condition characterized by periodic mood changes, euphoria, and disinhibition, usually accompanied by cognitive and functional impairment. The core criterion for the diagnosis of BD. I require a manic episode, whereas a depressive and at least one hypomanic episode is needed for the diagnosis of BD II [3]. The estimated prevalence of BD may range in adult life from 2.8 to 6.5 percent [4] and in subjects older than 65 years from 0.1 to 0.5% [5, 6]. Episodes of mania or hypomania are deemed frequent and reported in 5 and 7% of young adults, respectively [7], albeit the prevalence in elderly subjects is not fully known

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