title: Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer's disease.
abstract: Hippocampal atrophy and posterior cingulate hypometabolism are common features of both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). These regions show correlated activity at rest as part of the 'default network', and they are connected by the cingulum, a white matter (WM) tract. We hypothesised that hippocampal atrophy would be associated with disruption of the cingulum, as determined by diffusion tensor imaging. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with a T1 weighted 3D sequence and diffusion tensor FLAIR imaging. The T1 images were segmented into grey and white matter and spatially normalised using SPM. Hippocampal atrophy was estimated by calculating the mean grey matter (GM) volume from a region of interest in standard space and global atrophy from the total CSF segmentation. Fractional anisotropy (FA) maps were calculated and also spatially normalised. Using SPM, a multivariate correlation of FA against hippocampal GM, global atrophy and disease group was performed. We found a bilateral region adjacent to the posterior cingulate and encompassing a branch of the cingulum where global atrophy correlated with fractional anisotropy, after controlling for diagnosis and hippocampal GM. The results suggest that dementia disease progression as measured by global atrophy is associated with disruption of the white matter which connects posterior cingulate and lateral parietal regions. Hence, in addition to the hypometabolism in these regions in AD and DLB, there is also disruption to the white matter connecting them. Future studies are needed to determine whether the disruption precedes or is consequent on atrophy or hypometabolism.
authors.affiliation: Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK. m.j.firbank@ncl.ac.uk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Firbank
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Mani S
authors.initials: MS
authors.lastname: Krishnan
authors.forename: Andrew
authors.initials: A
authors.lastname: Teodorczuk
authors.forename: Philip
authors.initials: P
authors.lastname: English
authors.forename: Anil
authors.initials: A
authors.lastname: Gholkar
authors.forename: Roger
authors.initials: R
authors.lastname: Harrison
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D016880:Anisotropy; D001284:Atrophy; D038524:Diffusion Magnetic Resonance Imaging; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007089:Image Enhancement; D007091:Image Processing, Computer-Assisted; D020961:Lewy Body Disease / Q000175:diagnosis* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009415:Nerve Net / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology