Abstract
Amyloid-β (Aβ) and cerebral small vessel disease (CSVD) commonly coexist. They can occur independently by chance, or may interact with each other. We aimed to determine whether the distribution of Aβ in subcortical vascular cognitive impairments (SVCI) patients can be classified by the underlying pathobiologies. A total of 45 11C-Pittsburgh compound B PET positive (PiB(+)) SVCI patients were included in this study. They were classified using a new cluster analysis method which adopted the Louvain method, which finds optimal decomposition of the participants based on similarity of relative Aβ deposition pattern. We measured atherosclerotic cerebral small vessel disease (CSVD) markers and cerebral amyloid angiopathy (CAA) markers. Forty-five PiB(+) SVCI patients were classified into two groups: 17 patients with the characteristic Alzheimer’s disease like Aβ uptake with sparing of occipital region (OccSp) and 28 patients with occipital predominant Aβ uptake (OccP). Compared to OccSp group, OccP group had more postive association of atherosclerotic CSVD score (p for interaction = 0.044), but not CAA score with occipital/global ratio of PiB uptake. Our findings suggested that Aβ positive SVCI patients might consist of heterogeneous groups with combined CSVD and Aβ resulting from various pathobiologies. Furthermore, atherosclerotic CSVD might explain increased occipital Aβ uptakes.
Highlights
Louvain method, which finds optimal decomposition of the participants based on similarity of relative Aβ deposition pattern
We found that Pittsburgh compound B (PiB)(+) subcortical vascular cognitive impairment (SVCI) patients were clustered into two groups: one with a characteristic Alzheimer’s disease (AD)-like Aβ uptake pattern with sparing of occipital regions (OccSp), and one with occipital predominant Aβ uptake (OccP)
We found that the association between atherosclerotic cerebral small vessel disease (CSVD) score and occipital/global PiB standardized uptake value ratios (SUVR) ratio was more positive in the OccP compared to the occipital sparing (OccSp) group
Summary
Louvain method, which finds optimal decomposition of the participants based on similarity of relative Aβ deposition pattern. Atherosclerotic CSVD may decrease clearance of amyloid via perivascular lymphatic drainage[6] These possible pathobiologies might contribute to heterogeneous patterns of Aβ accumulation, depending on which is more predominant in patients with cognitive impairment. Given that Aβ may independently develop regardless of ischemia, Aβ might accumulate in an AD-like characteristic pattern yielding an occipital sparing (OccSp) PiB(+) SVCI; when Aβ and CSVD happen to interact with each other, Aβ might be more preferentially deposited in occipital regions, producing an occipital predominant (OccP) PiB(+) SVCI. We further hypothesized that CAA and atherosclerotic CSVD markers would be more strongly associated with increased occipital PiB uptake in OccP PiB(+) SVCI compared with OccSp PiB(+) SVCI patients
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