A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia

Abstract

Objective-To evaluate neurotransmitter deficiencies and neurotransmitter-based treatments for frontotemporal dementia (FTD).Methods-The authors conducted a systematic review of the literature on the mechanism and treatment of FTD and a meta-analysis of treatment studies of antidepressants for the behavioral symptoms of FTD.Results-Patients with FTD show deficiencies in the serotonin and dopamine neurotransmitter systems, while the acetylcholine system appears relatively intact. Antidepressant treatment significantly improves behavioral symptoms in FTD, but most studies are small and uncontrolled. Serotonergic treatments appear to improve the behavioral but not cognitive symptoms of FTD.Conclusions-Studies of neurotransmitter deficiencies in frontotemporal dementia (FTD) can be helpful in developing treatments. Treatment studies on FTD are scarce, given the prevalence and severity of this illness. Larger, well-controlled treatment studies are required to reach more definitive conclusions about treatment efficacy. Multicenter studies are likely the best way to complete treatment studies in a timely manner.Frontotemporal dementia (FTD) is increasingly recognized as an important cause of dementia. 1 The symptoms of FTD include behavioral symptoms such as disinhibition, inappropriate social behavior, and apathy. Other symptoms include language and executive dysfunction. 2,3 The behavioral symptoms of FTD can be difficult to manage for caregivers and clinicians.The paucity of pharmacologic trials for FTD is likely due to the only recent clinical definition of the illness, limitations in understanding the biology of FTD, and the difficulty of assembling well-characterized groups of patients.

Dementia syndromes: evaluation and treatment

“…Although the pathophysiology is not fully understood, FTD interestingly shows serotonergic deficits with relative sparing of acetylcholine function [40,201]. Patients with PD are often younger than those with AD (<65 years of age) and may progress faster with their disease.…”

No effect of DC brain polarization on verbal fluency in patients with advanced frontotemporal dementia

“…Frontotemporal dementia (FTD) comprises a set of disorders affecting the frontal and/or the anterior temporal lobes of the brain that present with behavioral and cognitive symptoms (Lund/Manchester, 1994), including impaired verbal fluency (the ability to generate words within a specific category) (Perri et al, 2005), which depends substantially on prefrontal cortex function (Stuss et al, 1998). To date, no effective treatment for the cognitive deficits in FTD has been found (Huey et al, 2006). Using letter-cued verbal fluency as the primary therapeutic outcome, we undertook a double-blinded, controlled trial of DC polarization in FTD.…”

Association study to evaluate the serotonin transporter and apolipoprotein E genes in frontotemporal lobar degeneration in Italy

“…For rs4795541, we found a significant difference between CT and FTLD, the presence of at least one S-allele associating to an increased FTLD risk of 2.1 times. Interestingly, a 5-HT deficit in FTLD was reported by autopsy, imaging and biochemical studies that evaluated the CSF content of 5-hydroxyindoleacetic acid (5-HIAA, a 5-HT metabolite) (Huey et al 2006).…”