Precision Medicine for Frontotemporal Dementia

Abstract

Frontotemporal dementia (FTD) is a common young-onset dementia presenting with heterogeneous and distinct syndromes. It is characterized by progressive deficits in behavior, language, and executive function. The disease may exhibit similar characteristics to many psychiatric disorders owing to its prominent behavioral features. The concept of precision medicine has recently emerged, and it involves neurodegenerative disease treatment that is personalized to match an individual's specific pattern of neuroimaging, neuropathology, and genetic variability. In this paper, the pathophysiology underlying FTD, which is characterized by the selective degeneration of the frontal and temporal cortices, is reviewed. We also discuss recent advancements in FTD research from the perspectives of clinical, imaging, molecular characterizations, and treatment. This review focuses on the approach of precision medicine to manage the clinical and biological complexities of FTD.

Keywords: frontotemporal dementia; frontotemporal lobar degeneration; genetics; neuroimaging; precision medicine; primary progressive aphasia.

Figure 1

Patterns of brain atrophy in clinical subtypes of frontotemporal dementia (–9). (A) Areas of brain atrophy in behavioral-variant frontotemporal dementia (blue), right hemisphere lateral view; (B) Areas of brain atrophy in semantic-variant primary progressive aphasia(green), left hemisphere lateral view; (C) Areas of brain atrophy in non-fluent variant primary progressive aphasia, left hemisphere lateral view.

Figure 2

Clinical, pathological, and genetic associations in FTD (–9, 37). Clinical symptoms are shown at left, colored regions of clinical diagnosis represent relative percentages of patients found to have each underlying neuropathological diagnosis. Blue line, genetic and pathological aspects of bvFTD; gray line, genetic, and pathological aspects of nfvPPA; purple line, genetic, and pathological aspects of svPPA. bvFTD, behavioral-variant frontotemporal dementia; svPPA, semantic-variant primary progressive aphasia; nfvPPA, non-fluent variant primary progressive aphasia; FUS, fused in sarcoma; TDP-43, transactive response (TAR) DNA-binding protein of 43 kDa; C9orf72, chromosome 9 open reading frame 72; GRN, progranulin mutations; MAPT, microtubule-associated protein tau; and VCP, valosin-containing protein.