Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia

Abstract

IMPORTANCE Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD.OBJECTIVE To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD.

Tweaking Progranulin Expression: Therapeutic Avenues and Opportunities

“…The current development and utilization of GRN therapy in FTD patients with GRN mutations provides a unique starting point for further research. The recent extensive documentation of fluid, neuroimaging and cognitive biomarkers for FTD will undoubtedly prove to be crucial in monitoring treatment response and guiding therapeutic development (Benussi et al, 2021;Panman et al, 2021). Additionally, specific biomarkers for the biological effects of GRN are needed to identify candidate diseases for GRN therapy.…”

Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

“…During this phase, psychiatric symptoms may frequently occur. Depressive symptoms are reported in AD prior to mild cognitive impairment (MCI) with a prevalence of about 20% [ 28 , 31 ], as well as in preclinical bvFTD, where a prevalence up to 40% has been described [ 23 , 32 ]. Depression during the preclinical stages of AD and bvFTD can be often associated with other affective symptoms and mood changes [ 15 , 33 ].…”

“…Apathy is characterized by multidimensional symptoms and can define a clinical syndrome per se, even in the absence of co-morbid depression [ 25 , 29 , 49 ]. In early AD, apathy shows a prevalence that reaches 70% [ 50 , 51 ] and is more typically characterized by the loss of motivation and executive dysfunction [ 52 , 53 ], whilst in bvFTD apathy occurs in up to 80% cases [ 32 , 54 ], presenting itself with a more frequent emotional profile [ 55 ]. Apathy also occurs in more than one third of subjects affected by PD and in a half of those with HD, typically leading to difficulties in organization and planning in these populations [ 56 , 57 , 58 ].…”

“…Moreover, psychosis frequently appears in middle and advanced stages of AD, mainly consisting of non-bizarre paranoid delusions and hallucinations, reaching a prevalence of 40% [ 63 ]. In bvFTD, OCS are also frequent, occurring in up to 60% of patients at later stages [ 32 , 64 ], and are more often represented by complex compulsive behaviors, while obsessions are less prevalent [ 65 ].…”

Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration

“…5,6 Along with heterogeneity in both clinical presentations and pathological hallmarks, an increasing literature depicts the complex figure of the genetic determinants of FTD, with up to 20-30% of the cases with mutations in progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. 7 This heterogeneity, 8 as well the lack of a clear-cut relationship between clinical phenotypes, 9 genetic traits and neuropathological features, represent the main obstacle hampering the development of a unifying pathogenetic model and, as consequence, of disease-modifying strategies of intervention.…”