title: Neural substrates of cognitive and behavioral deficits in atypical Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive cognitive decline that typically affects first memory and later executive functions, language, and visuospatial skills. This sequence of cognitive deterioration is thought to reflect the progressive invasion of the cerebral cortex by the two major pathological hallmarks of AD, neurofibrillary tangles (NFT) and senile plaques (SP), as well as degree of neuronal and synaptic loss. In atypical AD, prominent and early deficits are found in language, motor abilities, frontal and executive capacities, or visuospatial skills. These atypical clinical features are associated with an unusual pattern of NFT or SP formation that predominantly involves cortical areas usually spared in the course of the degenerative process. In an attempt to classify this highly heterogeneous subgroup, the present article provides an overview of clinicopathological analyses in patients with atypical progression of AD symptomatology with special reference to the relationship between specific cognitive and behavioral deficits and hierarchical patterns of AD lesion distribution within the cerebral cortex. On the basis of these representative examples of a cortical circuit-based approach to explore the mechanisms giving rise to AD neuropsychological expression, we also critically discuss the possibility to develop a matrix linking clinical presentations to degeneration of forward and backward long corticocortical pathways in this disorder.
authors.affiliation: Division of Old Age Psychiatry, Department of Psychiatry-CHUV, Prilly-Lausanne, Switzerland. Armin.Von-Gunten@chuv.ch
authors.forename: Armin
authors.initials: A
authors.lastname: von Gunten
authors.forename: Constantin
authors.initials: C
authors.lastname: Bouras
authors.forename: Enikö
authors.initials: E
authors.lastname: Kövari
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Giannakopoulos
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology* / Q000523:psychology; D001526:Behavioral Symptoms / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology