{"title":"The role of cognitive reserve in white matter hyperintensities: from cognitive aging to Alzheimer's spectrum.","authors":"Yu-Ruei Lin, Wei-Lu Lee, Jong-Ling Fuh","doi":"10.1002/dad2.70167","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>White matter hyperintensities (WMHs) are characteristic of Alzheimer's disease (AD), and cognitive reserve (CR) protects cognitive function. However, whether WMHs mediate the CR-cognition relationship remains unclear.</p><p><strong>Methods: </strong>Brain imaging, clinical features, and neuropsychological assessments were performed, and CR was measured using the Cognitive Reserve Index questionnaire. Bootstrap mediation analysis examined CR's role in specific cognitive functions, controlling for covariates.</p><p><strong>Results: </strong>Participants who were cognitively unimpaired (CU; <i>n</i> = 85, mean age = 68.6 ± 5.7) and who had mild cognitive impairment (MCI; <i>n</i> = 43, mean age = 71.8 ± 6.5) or AD (<i>n</i> = 61, mean age = 72.8 ± 6.2) were included. CR was positively associated with global and non-memory cognitive functions in the CU and MCI groups. In the CU group, WMHs served as a mediator between CR and global cognitive ability.</p><p><strong>Discussion: </strong>CR may maintain the optimal cognitive function by mitigating the WMH burden independently of AD-related brain changes.</p><p><strong>Highlights: </strong>Cognitive reserve (CR) positively links to non-memory cognition.Cognitive reserve mitigates white matter hyperintensities to preserve cognition.Cognitive reserve primarily protects cognition in pre-Alzheimer's stages.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 3","pages":"e70167"},"PeriodicalIF":4.4000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373489/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70167","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: White matter hyperintensities (WMHs) are characteristic of Alzheimer's disease (AD), and cognitive reserve (CR) protects cognitive function. However, whether WMHs mediate the CR-cognition relationship remains unclear.
Methods: Brain imaging, clinical features, and neuropsychological assessments were performed, and CR was measured using the Cognitive Reserve Index questionnaire. Bootstrap mediation analysis examined CR's role in specific cognitive functions, controlling for covariates.
Results: Participants who were cognitively unimpaired (CU; n = 85, mean age = 68.6 ± 5.7) and who had mild cognitive impairment (MCI; n = 43, mean age = 71.8 ± 6.5) or AD (n = 61, mean age = 72.8 ± 6.2) were included. CR was positively associated with global and non-memory cognitive functions in the CU and MCI groups. In the CU group, WMHs served as a mediator between CR and global cognitive ability.
Discussion: CR may maintain the optimal cognitive function by mitigating the WMH burden independently of AD-related brain changes.
Highlights: Cognitive reserve (CR) positively links to non-memory cognition.Cognitive reserve mitigates white matter hyperintensities to preserve cognition.Cognitive reserve primarily protects cognition in pre-Alzheimer's stages.
期刊介绍:
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.