Frontal lobe dementia and motor neuron disease

Frontal lobe dementia (FLD) (syn. frontotemporal dementia and dementia of frontal type) is a generic term that describes a clinical syndrome in which patients manifest a profound breakdown in personality and social conduct, together with adynamic spontaneous speech, culminating in mutism. This pattern of cognitive impairment implicates bilateral frontal lobe dysfunction, an assumption supported by functional neuroimaging findings of anterior cerebral abnormality. Patients with FLD can go on to develop motor neuron disease (FLD-MND), although the clinical features of MND may accompany or occasionally precede the onset of dementia. The emergence of MND is responsible for death within 3 years of onset. Frontotemporal lobar pathology in FLD-MND is characterized by loss of large cortical neurons, spongiform change and mild astrocytic gliosis. Ubiquitinated (but not tau-positive) inclusions are present within the frontal cortex. There is severe nigral cell loss (without Lewy bodies), and marked hypoglossal and spinal motor neuron degeneration, together with ubiquitinated (but not tau-positive) inclusions within the spinal neurons. Some authors suggest that FLD-MND is a separate disease entity, whereas others suggest it represents an interface between FLD and "classic" (non-dementing) motor neuron disease (CMND). An association with CMND is supported by findings in these patients of failure in tasks sensitive to "frontal lobe" dysfunction, and patterns of functional neuroimaging abnormality which are identical in distribution, but less severe than those encountered in FLD-MND. However, the nosological status of FLD-MND remains enigmatic in the absence of defined pathological and molecular markers.