title: Amyloid-β and cognition in aging and Alzheimer's disease: molecular and neurophysiological mechanisms.
abstract: Amyloid-β (Aβ) deposition in the brain is one of the key pathological features of Alzheimer's disease (AD). Neither traditional clinical-pathological studies nor modern in vivo biomarker investigations of brain amyloid load, however, could reveal a convincing relationship between brain Aβ load and cognitive deficits and decline in patients with AD. Evidence suggests that pathophysiological Aβ dysregulation and accumulation are very early events that precede the onset of cognitive impairment reaching a plateau at the clinical stage of the beginning dementia syndrome. Therefore, research efforts have focused on the role of Aβ in asymptomatic older adults: the results of combined amyloid-PET and neuropsychological studies show a modest but significant correlation between brain fibrillar amyloid load and various subtle cognitive deficits, most notably in challenging episodic associative memory tasks. In order to elucidate the pathophysiological link between cognition and Aβ, a number of combined functional neuroimaging studies have been performed, resulting in early and complex functional alterations in cognitively relevant neural networks such as the default mode network and the largely overlapping episodic memory networks. Multimodal studies using amyloid-tracing imaging methods and neurodegeneration biomarkers strongly suggest that neural network discoordination is specifically related to Aβ-mediated functional and potentially reversible disruption of synaptic plasticity rather than a direct consequence to neurodegenerative pathological processes. These pathophysiological processes and mechanisms may dynamically and non-linearly evolve through fully reversible adaptive compensatory stages and through reactive decompensatory stages into fully irreversible neurodegenerative stages of AD.
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany. Harald.Hampel@med.uni-muenchen.de
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003071:Cognition; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D006801:Humans; D011877:Radionuclide Imaging
chemical_list: D016229:Amyloid beta-Peptides