Distinct amyloid distribution patterns in amyloid positive subcortical vascular cognitive impairment

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.

Development and clinical validation of CT-based regional modified Centiloid method for amyloid PET

“…Since our common target regions included parts of the occipital region, we calculated rdcCL in the occipital region. This has some clinical implication because cerebrovascular disease might be related to increased Aβ uptake in the occipital region [22,23]. However, the method developed in the present study provides regional as well as global rdcCL scales in the six regions including the striatum.…”

Interaction between Alzheimer’s Disease and Cerebral Small Vessel Disease: A Review Focused on Neuroimaging Markers

“…Another study using clustering analyses classified SVCI patients and AD patients into the Aβ occipital-predominant and Aβ occipital-sparing groups. The frequency of the occipital-predominant group has been shown to be higher in SVCI patients (62.2%) than in AD patients (37.8%) [ 33 ]. Furthermore, the Aβ spreading pattern in patients with SVCI is quite different from in patients with ADCI.…”

“…Specifically, the Aβ spreading pattern of patients with SVCI demonstrates that Aβ accumulates in the occipital area before the temporal and frontal regions, whereas in patients with ADCI, the parietal and fronto-temporal regions precede the occipital region. ( Figure 1 a) [ 33 , 54 , 55 , 56 , 57 ]. The predominant Aβ deposition in the occipital region, mainly observed in patients with SVCI, may be related to the distribution pattern of CAA or ischemic vulnerability of the posterior circulation [ 53 ].…”

“…Among patients with dementia, 38.0% (19/50) have AD and infarcts, 30.0% (15/50) have pure AD, and 12% (6/50) have vascular dementia [ 9 ]. The association between AD and CSVD could be explained by the possibility that CSVD hampers the clearance of Aβ [ 32 , 33 , 34 ].…”

Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment

“…The aberrant deposition of Aβ in ADCI is related to the decreased Aβ clearance; specifically, decreased Aβ clearance can result from impaired microglial function, enzymatic degradation, perivascular Aβ drainage, and the blood–brain barrier (BBB) function ( Grimmer et al, 2012 ; Tarasoff-Conway et al, 2015 ). We previously revealed that patients with SVCI showed predominant Aβ deposition in the occipital lobe ( Jang et al, 2018 ) and WMHs were associated with Aβ deposition, particularly in posterior brain regions ( Noh et al, 2014 ). Considering that the posterior regions are vulnerable to ischemic injury, the CSVD burden may impaired Aβ clearance by creating a deficiency in perivascular Aβ drainage and in the BBB ( Grinberg and Thal, 2010 ; Zlokovic, 2011 ).…”