title: Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies.
abstract: Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-β deposition as measured with11C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-β deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-β deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline11C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent11C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on three-dimensional T1-weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline11C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline11C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P < 0.05). Greater baseline11C-Pittsburgh compound B standard unit value ratio was also associated with greater ventricular expansion rates (P < 0.01) and greater worsening over time in Clinical Dementia Rating Scale, sum of boxes (P = 0.02). In conclusion, in patients with probable dementia with Lewy bodies, higher amyloid-β deposition at baseline is predictive of faster neurodegeneration in the cortex and also in the striatum. This distribution is suggestive of possible interactions among amyloid-β, tau and α-synuclein aggregates, which needs further investigation. Furthermore, higher amyloid-β deposition at baseline predicts a faster clinical decline over time in patients with probable dementia with Lewy bodies.
authors.affiliation: 1 Department of Radiology, Mayo Clinic, Rochester, MN, USA 2 Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy 3 Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sarro
authors.affiliation: 1 Department of Radiology, Mayo Clinic, Rochester, MN, USA 4 Department of Information Technology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: 5 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Lundt
authors.affiliation: 5 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Przybelski
authors.affiliation: 5 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.affiliation: 6 Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Graff-Radford
authors.affiliation: 6 Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: 1 Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: 7 Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Tanis J
authors.initials: TJ
authors.lastname: Ferman
authors.affiliation: 6 Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: 3 Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: 2 Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy 3 Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: 5 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA 6 Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: 1 Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: 1 Department of Radiology, Mayo Clinic, Rochester, MN, USA kantarci.kejal@mayo.edu.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000639:trends; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography / Q000639:trends
chemical_list: D016229:Amyloid beta-Peptides
keywords: DLB; amyloid imaging; beta-amyloid; brain atrophy; structural MRI