Studies on amyloid burden in PiB(+) subcortical vascular cognitive impairment

Abstract

Introduction: Previous studies demonstrated that patients who had been clinically diagnosed as subcortical vascular cognitive impairment (SVCI) proved to have co-associated Alzheimer's disease (AD) pathologies. In this study, our interest are white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11C-Pittsburgh compound B (PiB) PET in PiB(+) SVCI, that is, the dementia with both vascular and amyloid pathologies. We aimed 1) to evaluate the effects of ApoE4 genotype on the relationship between WMH and amyloid burden

2) to explore the distribution of amyloid burden

3) to evaluate the effects of amyloid burden on the cortical atrophy or cognitive impairment. Methods: We prospectively recruited 253 subjects who were clinically diagnosed with AD, SVaD, aMCI, or svMCI who underwent 11C-PiB positron emission tomography (PET) scan and 3.0-Tesla MRI at Samsung Medical Center between September 2008 and May 2011. Among them, we included only PiB(+) patients as study subjects. 1) To evaluate the relationship between the volume of WMH and PiB retention, we used multiple linear regression and voxel-based analysis to identify regions with a correlation between volume of WMH and PiB retention. 2) To identify the patterns of amyloid retention, we used voxel-based analysis with SPM. 3) We used multiple linear regression analysis to evaluate the effects of amyloid burden on cortical thickness measured by surface based morphometry analysis. Results: 1) In the ApoE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention, especially in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. 2) Distribution of amyloid retention in PiB(+) SVCI had characteristic pattern: increased left-right asymmetry, increased anterior-posterior asymmetry, increased retention in occipital area, decreased retention in striatum compared to ADCI. 3) In PiB(+) SVCI, amyloid burden had tendency to be related to cortical atrophy in medial temporal and anterior cingulated cortices. In addition, memory, language, global cognitive functions were associated with amyloid retention in these patients. Conclusions: Our results suggested WMH are correlated with amyloid burden especially in the posterior brain regions in ApoE4 non-carriers. However, this correlation was not observed in ApoE4 carriers, perhaps because in these subjects the influence of ApoE4, which causes earlier development of AD, overrides the effect of CVD. Distinct patterns of amyloid distribution and effects of amyloid burden on cortical atrophy or cognitive impairment suggested the pathomechanism of amyloid retention in PiB(+) SVCI, which explained severe WMH may lead to amyloid retention in the patients with SVCI.