Neurotransmitter Dysfunction and Neurotransmitter Replacement Therapy as Part of Frontotemporal Dementia Treatment

Abstract

Very few studies on the neurotransmitter systems involved in frontotemporal dementia (FTD) have been published. No cholinergic deficiency is associated with FTD. Correlating non-specific, serotoninergic dysfunction and behavioral disorders permitted developing clinical trials on selective serotonin reuptake inhibitors (SSRIs). All five trials included a limited number of patients. Two preliminary trials involving the treatment of cognitive and attentional dysfunctions by noradrenergic agents were also developed on the hypothesis that noradrenergic system dysfunction was associated with FTD. Replacement neurotransmitter therapy to treat behavioral and cognitive symptoms in FTD has, however, proved disappointing so far. The pathophysiology of FTD is still poorly understood. Abnormalities linked to the tau protein level and excitotoxicity have been hypothesised. The most promising biological therapy would currently be to inhibit tau protein aggregation. Developing clinical trials on neuroprotective drugs will therefore require prior development of rating scales specific to this essentially behavioral type of dementia.