{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:05:12Z","timestamp":1769756712139,"version":"3.49.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prospective longitudinal cohort study enrolled community-dwelling older adults (\u226565 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected from January 1, 2015, to December 31, 2024 (mean [SD] follow-up, 5.6 [1.8] years), with annual cognitive and clinical assessments.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Total and regional WMH volumes, cognitive status change, and antihypertensive medication use.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Monthly driving trip frequency, trip distance, unique destinations, driving entropy, and safety events. Longitudinal associations were evaluated using linear mixed-effects models adjusted for demographic characteristics, socioeconomic status, and vascular risk.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 220 participants (mean [SD] age, 72.9 [5.0] years; 119 men [54%]) with low vascular risk (mean [SD] Framingham Stroke Risk Profile, 6.4% [1.3%]), greater baseline WMH burden was correlated with lower driving frequency (\u03b2\u2009=\u2009\u22120.16; 95% CI, \u22120.27 to \u22120.06;\n P<\/jats:italic>\n \u2009=\u2009.002), reduced driving entropy (\u03b2\u2009=\u2009\u22120.17; 95% CI, \u22120.27 to \u22120.06;\n P<\/jats:italic>\n \u2009=\u2009.002), and fewer unique destinations (\u03b2\u2009=\u2009\u22120.17; 95% CI, \u22120.27 to \u22120.07;\n P<\/jats:italic>\n \u2009=\u2009.001). Longitudinally, higher WMH was associated with faster declines in driving frequency (\u03b2\u2009=\u2009\u22120.08; 95% CI, \u22120.13 to \u22120.04;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), entropy (\u03b2\u2009=\u2009\u22120.11; 95% CI, \u22120.17 to \u22120.06;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), and unique destinations (\u03b2\u2009=\u2009\u22120.09; 95% CI, \u22120.14 to \u22120.04;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Growth in posterior WMH burden showed the strongest association with increased crash risk (\u03b2\u2009=\u20091.71; 95% CI, 1.17-2.24;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) among those developing cognitive impairment (38 [17%]). Among participants, 135 used antihypertensive therapy and 113 underwent follow-up MRI. Antihypertensive therapy, particularly angiotensin-converting enzyme inhibitors, was associated with attenuated WMH-related risky driving before adjustment, but not after adjustment (\u03b2\u2009=\u2009\u22120.17; 95% CI, \u22120.37 to 0.03; unadjusted\n P<\/jats:italic>\n \u2009=\u2009.02; false discovery rate\u2013adjusted\n P<\/jats:italic>\n \u2009=\u2009.08). Sensitivity analyses confirmed associations were independent of Alzheimer dementia pathology.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of older drivers, higher WMH burden, especially in posterior regions, was associated with progressive driving self-regulation and increased errors in those developing cognitive impairment. Antihypertensive use attenuated WMH-associated unsafe driving. Posterior WMH may represent a biomarker for identifying older drivers at risk and may inform mobility-preserving interventions in aging populations.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.54501","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T16:30:31Z","timestamp":1769704231000},"page":"e2554501","source":"Crossref","is-referenced-by-count":0,"title":["White Matter Hyperintensity Burden and Decline in Driving Performance Among Older Adults"],"prefix":"10.1001","volume":"9","author":[{"given":"Madhur","family":"Parihar","sequence":"first","affiliation":[{"name":"Barrow Neuro Analytics Center, Barrow Neurological Institute, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, 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