White matter hyperintensity on MRI and plasma Aβ42/40 ratio additively increase the risk of cognitive impairment in hypertensive adults.

Pubmed ID: 39229896

Pubmed Central ID: PMC11485393

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association

Publication Date: Oct. 1, 2024

MeSH Terms: Humans, Male, Female, Aged, Risk Factors, Middle Aged, Hypertension, Magnetic Resonance Imaging, Peptide Fragments, Amyloid beta-Peptides, White Matter, Cognitive Dysfunction

Grants: UL1 TR001863, K23 NS105924, U01 NS106513, R01 NR018335, U24 NS107215, U24 NS107136, R01 AG055606, R01NS130189, UG3NS130228, P30 AG066462, R01 NS130189, K23 NS121634, R38 HL167282, K23NS105924, R01NR018335, U01NS106513, K23NS123340, K23NS121634, R01 MD016178, R01NS110721, K23 NS123340, UG3 NS130228, U24NS107136, U24AG082930, R01AG055606, U24 AG082930, HT9425-23-1-0981, 1R38HL167282-01, U24NS107215, W81XWH-21-1-0590, U24NS129500, R01 AG065805, R01 NS110721, R01MD016178, U24 NS129500, R01AG065805, R01EB301114

Authors: Pajewski NM, Gottesman RF, Schneider ALC, Brickman AM, de Havenon A, Stulberg E, Sheth KN, Prabhakaran S, Rost N, Falcone GJ, Littig L, Sharma R, Willamson JD, Li V

Cite As: de Havenon A, Gottesman RF, Willamson JD, Rost N, Sharma R, Li V, Littig L, Stulberg E, Falcone GJ, Prabhakaran S, Schneider ALC, Sheth KN, Pajewski NM, Brickman AM. White matter hyperintensity on MRI and plasma Aβ42/40 ratio additively increase the risk of cognitive impairment in hypertensive adults. Alzheimers Dement 2024 Oct;20(10):6810-6819. Epub 2024 Sep 4.

Studies:

Abstract

INTRODUCTION: Dementia often involves comorbid Alzheimer's and vascular pathology, but their combined impact warrants additional study. METHODS: We analyzed the Systolic Blood Pressure Intervention Trial and categorized white matter hyperintensity (WMH) volume into highest versus lowest/mid tertile and the amyloid beta (Aβ)42/40 ratio into lowest versus mid/highest ratio tertile. Using these binary variables, we created four exposure categories: (1) combined low risk, (2) Aβ risk, (3) WMH risk, and (4) combined high risk. RESULTS: In the cohort of 467 participants (mean age 69.7 ± 7.1, 41.8% female, 31.9% nonwhite or Hispanic) during 4.8 years of follow-up and across the four exposure categories the rates of cognitive impairment were 5.3%, 7.8%, 11.8%, and 22.6%. Compared to the combined low-risk category, the adjusted hazard ratio for cognitive impairment was 4.12 (95% confidence interval, 1.71 to 9.94) in the combined high-risk category. DISCUSSION: This study emphasizes the potential impact of therapeutic approaches to dementia prevention that target both vascular and amyloid pathology. HIGHLIGHTS: White matter hyperintensity (WMH) and plasma amyloid (Aβ42/40) are additive risk factors for the development of cognitive impairment in the SPRINT MIND trial. Individuals in the high-risk categories of both WMH and Aβ42/40 had a near fivefold increase in risk of cognitive impairment during 4.8 years of follow-up on average. These findings suggest that treatment strategies targeting both vascular health and amyloid burden warrant further research.