Comparative Cognitive Neuropsychological Studies of Frontal Lobe Function: Implications for Therapeutic Strategies in Frontal Variant Frontotemporal Dementia

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Abstract
Patients with mild frontal variant frontotemporal dementia (fvFTD) who attend the clinic are usually unaware of the pervasive changes in their personality and behaviour, despite the fact it is these changes which have prompted the referral from the patient’s spouse or carer. Comparative studies across various species offer unique insights into the heterogeneous structure and functions of the prefrontal cortex, and can allow a novel approach to the precise identification of the neuropsychological deficits present in these patients. We have found that they may show marked deficits on tests sensitive to ventromedial prefrontal or orbitofrontal function, in the relative absence of impairments on tests sensitive to dorsolateral prefrontal function. We highlight important differences in the neurocognitive profile of these patients with that of patients with other neurodegenerative conditions, including basal ganglia diseases and dementia of the Alzheimer type. The specific nature of these neuropsychological deficits, together with converging evidence from clinical and neuropathological studies, may provide useful clues about the predominant locus of dysfunction in the early stages of fvFTD and possible underlying neurotransmitter abnormalities. This is important for the successful development of therapeutic intervention strategies for both cognitive and behavioural symptoms in fvFTD. Finally, we evaluate critically the rationales for therapeutic modulation of noradrenergic, serotonergic and dopaminergic neurotransmitter systems at various stages of disease.