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Abstract BACKGROUNDLimited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians. METHODSVascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally. RESULTSBaseline analyses revealed that amyloid‐negative (Aβ–) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ– CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups. CONCLUSIONOur findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ– individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid‐positive individuals had worse cognitive performance than Aβ– individuals. HighlightsVascular risk significantly affects cognition in amyloid‐negative older Koreans.Amyloid‐negative CN older adults with high vascular risk had lower baseline cognition.Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk.The study underscores the impact of vascular health on the AD disease spectrum.
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This content will become publicly available on June 1, 2026
Arteriolar degeneration and stiffness in cerebral amyloid angiopathy are linked to Aβ deposition and lysyl oxidase
INTRODUCTION: The morphological and molecular changes associated with the degeneration of arterioles in cerebral amyloid angiopathy (CAA) are incompletely understood. METHODS: Post mortem brains from 26 patients with CAA or neurological controls were analyzed using light-sheet microscopy, and morphological features of microvascular degeneration were quantified using surface volume rendering. Vascular stiffness was analyzed using atomic force microscopy. RESULT: Vascular smooth muscle cells (VSMCs) volume was reduced by ≈ 55% inCAA. This loss of VSMC volume correlated with increased arteriolar diameter, variability in diameter, and the volume of amyloid beta (Aβ) deposition in the vessel. Vessels with CAA were > 300% stiffer than controls. The volume of extracellular matrix cross-linking enzyme lysyl oxidase (LOX) correlated closely with vascular degenerative features. DISCUSSION: Our findings provide valuable insights into the connections among LOX, Aβ deposition, and vascular stiffness in CAA. Restoration of physiologic extracellular matrix properties in penetrating arteries may yield a novel therapeutic strategy for CAA.
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- Award ID(s):
- 1846860
- PAR ID:
- 10633222
- Publisher / Repository:
- Wiley Periodicals LLC
- Date Published:
- Journal Name:
- Alzheimer's & Dementia
- Volume:
- 21
- Issue:
- 6
- ISSN:
- 1552-5260
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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