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• W1982487895 abstract "In familial Alzheimer's disease (FAD), positron emission tomography (PET) studies using Pittsburgh compound B (PiB) have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. We investigate whether there are associated changes in the volume and diffusivity of these brain regions, and how they relate to cognitive function. Seven Presenilin 1 (PSEN1) gene mutation carriers (MCs) and eleven controls were studied (Table 1). The MCs were all presymptomatic or mildly affected by FAD and had undergone cognitive assessment and PiB-PET imaging, which demonstrated marked PiB retention, particularly in the thalamus and cerebellum. All subjects underwent volumetric and diffusion magnetic resonance imaging (MRI) at 3Tesla. The MRI data was analysed using Freesurfer (v4.4.0) to segment cortical and subcortical brain region volumes, which were then registered to the diffusion data. Linear regression models were used to assess differences in the volume and diffusion indices of subcortical brain regions between PSEN1 MCs and controls. After adjusting for gender, age and total intracranial volume, MCs demonstrated significantly smaller volumes of the left caudate by 0.67ml (95%CI 0.29,1.06 p = 0.002) adjacent left accumbens area by 0.13ml (95%CI 0.05,0.21 p = 0.003) and right caudate by 0.51ml (95%CI 0.12,0.89 p = 0.015). There was weaker evidence for a reduction in the volume of the left putamen by 0.45ml (95%CI -0.08,0.97 p = 0.092), right putamen by 0.41ml (95%CI -0.05,0.87, p = 0.075), left thalamus by 0.54ml (95%CI -0.04,1.11, p = 0.065), right thalamus by 0.38ml (95%CI -0.17,0.94, p = 0.160) and right accumbens area by 0.10ml (95%CI -0.01,0.20, p = 0.061). The only subcortical region demonstrating evidence of a difference in diffusivity between MCs and controls was the right thalamus, where MCs showed a reduction in axial diffusivity of 55.0μm2/s (95%CI -2,112 p = 0.059), radial diffusivity of 41.0μm2/s (95%CI -5,87 p = 0.077) and mean diffusivity (MD) of 45.7μm2/s (95%CI -3,94 p = 0.062). Within the group of PSEN1 MCs, increasing thalamic MD correlated with decreasing mini-mental state examination (MMSE) score. The early striatal and thalamic amyloid deposition witnessed in PSEN1 MCs is accompanied by reduced volumes of these brain regions. In the right thalamus, increased diffusivity indices suggest loss of tissue microstructural integrity and this appears to be associated with deteriorating cognitive function." @default.
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• W1982487895 date "2010-07-01" @default.
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• W1982487895 title "O3-06-03: Early subcortical amyloid deposition in familial Alzheimer's disease is accompanied by changes in tissue volume and diffusivity" @default.
• W1982487895 doi "https://doi.org/10.1016/j.jalz.2010.05.429" @default.
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