017 A network model of semantic dementia. Issue 3 (9th February 2012)

• Record Type: Journal Article
• Authors: Fletcher, P; Warren, J D
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 83:Issue 3(2012)
• Page Start: e1
• Page End: e1
• Publication Date: 2012-02-09
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2011-301993.59
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Semantic dementia (SD) is a unique syndrome in the frontotemporal lobar degeneration spectrum. Typically presenting as a progressive, fluent anomic aphasia, SD is the paradigmatic disorder of semantic memory with a characteristic anatomical profile of asymmetric, selective antero-inferior temporal lobe atrophy. Histopathologically, most cases show a specific pattern of abnormal deposition of protein TDP-43. This relatively close clinical, anatomical and pathological correspondence suggests SD as a promising target for future therapeutic trials. However, rational drug design and monitoring is likely to require a comprehensive understanding of how the molecular insult in SD translates to a clinico-anatomical phenotype. Here we propose a pathophysiological model of SD. The model is motivated by neuropsychological and neuroimaging data and posits the sequential, regionally determined disintegration of a vulnerable neural network. The key features of the model are: (1) existence of local zones of synaptic convergence within the temporal lobe with predictable network organisation; (2) a mechanism (or mechanisms) for transynaptic action of the molecular insult; and (3) establishment of a gradient of neuronal damage across the affected network, both within and between the temporal lobes. The model makes empirically testable predictions concerning the evolution of regional atrophy in SD.