Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups.

Clinical and neuropathological descriptions of patients with non-Alzheimer's disease atrophy of the frontotemporal lobes have emerged chiefly from Lund, Sweden and Manchester, UK. The nosology of both the clinical syndrome and the underlying histological change is in danger of becoming confused in the medical literature and terminological distinctions between clinical and pathological criteria are not always strictly kept. Accordingly, the workers in both centres have shared their clinical and pathological findings and have decided upon commonly agreed criteria for neuropsychiatric and pathological diagnosis. These are based on clinical evaluation of several hundreds of patients and upon pathological analysis of more than 60 brains. Together these represent the largest series in the world and have been the focus of interest in the two international conferences on Frontotemporal Dementia held in Lund in 1986' and 19922. Frontotemporal dementia is the prototypical behavioural disorder arising from frontotemporal cerebral atrophy and is associated in a few cases with the clinical manifestations of the amyotrophic form of motor neuron disease. Two types of histological change underlie the atrophy and both share an identical anatomical distribution in the frontal and temporal lobes. The commonest pathology is that of nerve cell loss and spongiform change (microvacuolation), together with a mild or moderately severe astrocytic gliosis in the outer cortical layers, and is designated frontal lobe degeneration. This is to distinguish it from the typical Pick-type histology characterised by intense astrocytic gliosis in the presence of intraneuronal inclusion bodies and inflated neurons in all cortical layers. Cases of frontotemporal dementia with a similar level of astrocytosis but without inclusions or inflated neurons should be best included in this Pick-type category pending a more definitive histological identification. When spinal motor neuron degeneration occurs, the cerebral pathology is almost always that of frontal lobe degeneration. This formulation distinguishes the clinical syndrome of frontotemporal dementia from other disorders that may also affect frontotemporal structures, such as Alzheimer's disease, Creutzfeldt-Jakob disease, subcortical vascular disease and Huntington's disease as well as affective and schizophreniform psychoses. The application of descriptive labels to the three major histological patterns avoids the imputation of aetiological significance. Future studies may indicate that there is a spectrum of non-specific histology involving both, or alternatively, that each may reflect a distinct process governed by different genetic or molecular mechanisms. To consider the Pick'stype of change as a histological variant of frontotemporal atrophy, manifesting clinically as frontotemporal dementia, avoids the vexed clinical and pathological arguments as to what constitutes, so-called "Pick's disease". Frontotemporal dementia results from bilateral and more or less symmetrical distribution of pathology in the frontotemporal lobes. Asymmetrical degeneration, however, may, influence the clinical picture. Predominant involvement of the language dominant frontal and temporal lobes leads to linguistic rather than behavioural symptoms.' 4 The clinical entity of progressive aphasia and the link between this condition and frontotemporal dementia is essentially determined anatomically, both forming part of the clinical spectrum of lobar atrophy and sharing the same spectrum of histology.5 The criteria for, and the different forms of language breakdown in, progressive aphasia are not discussed here. We describe the clinical and pathological criteria for frontotemporal dementia.