title: Memory binding and white matter integrity in familial Alzheimer's disease.
abstract: Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease.
authors.affiliation: 1 Human Cognitive Neuroscience, Psychology, University of Edinburgh, Edinburgh, UK 2 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 3 UDP-INECO Foundation Core on Neuroscience (UIFCoN), Diego Portales University, Santiago, Chile 4 Alzheimer Scotland Dementia Research Centre and Scottish Dementia Clinical Research Network, NHS Scotland 5 Neuroscience Group, University of Antioquia, Antioquia, Colombia mprodri1@staffmail.ed.ac.uk.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Parra
authors.affiliation: 1 Human Cognitive Neuroscience, Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Heini
authors.initials: H
authors.lastname: Saarimäki
authors.affiliation: 2 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: 5 Neuroscience Group, University of Antioquia, Antioquia, Colombia.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Londoño
authors.affiliation: 1 Human Cognitive Neuroscience, Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Lewis
authors.initials: L
authors.lastname: Pettit
authors.affiliation: 5 Neuroscience Group, University of Antioquia, Antioquia, Colombia.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.affiliation: 1 Human Cognitive Neuroscience, Psychology, University of Edinburgh, Edinburgh, UK 2 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Sergio
authors.initials: S
authors.lastname: Della Sala
authors.affiliation: 1 Human Cognitive Neuroscience, Psychology, University of Edinburgh, Edinburgh, UK 2 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 6 Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Abrahams
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000503:physiopathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer’s disease; biomarkers; memory; psychometry; structural MR imaging