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-b deposition as measured with 11 C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-b deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-b deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline 11 C-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 underwent 11 C-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 threedimensional T 1 -weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline 11 C-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 baseline 11 C-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 5 0.05). Greater baseline 11 C-Pittsburgh compound B standard unit value ratio was also associated with greater ventricular expansion rates (P 5 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-b 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-b, tau and a-synuclein aggregates, which needs further investigation. Furthermore, higher amyloid-b deposition at baseline predicts a faster clinical decline over time in patients with probable dementia with Lewy bodies. Keywords: DLB; structural MRI; beta-amyloid; amyloid imaging; brain atrophy Abbreviations: AChEI = acetylcholinesterase inhibitor; CDR-SOB = Clinical Dementia Rating scale, Sum of Boxes; DLB = dementia with Lewy bodies; MMSE = Mini-Mental State Examination; PiB = 11 C-Pittsburgh compound B; SUVR = standardized uptake value ratio; TBM-SyN = tensor-based morphometry using symmetric diffeomorphic image normalization; UPDRS-III =

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