ArticlePublished: 18 July 2026Yiqi Zhu1,2,David C. Brown ORCID: orcid.org/0000-0002-2493-636X1,Chen Chen1,Ramkrishna K. Singh1,Semere Bekena1,Beau M. Ances ORCID: orcid.org/0000-0003-3862-73971,Eric J. Lenze2,David B. Carr3,Jean-Francios Trani4,5,6,7 &…Ganesh M. Babulal ORCID: orcid.org/0000-0001-7966-35091,7,8,9 Molecular Psychiatry (2026) Cite this articleSave articleView saved researchSubjectsDepressionMolecular biologyPredictive markersAbstractDriving is a complex task that can be compromised by mood disorders and neurodegenerative conditions. Major depressive disorder (MDD) and Alzheimer’s disease (AD) increase in prevalence with older age. Preclinical AD, identified through protein biomarkers, is strongly associated with an increased risk of developing AD. This study tracked the daily driving behaviors of older adults over an average period of 54 months and found participants with MDD and Positron Emission Tomography (PET) biomarker tau had a faster increase in risky driving behaviors, such as hard braking, and a slower decline in randomness of driving patterns, compared to healthy controls. Notably, participants with MDD were more likely to exhibit PET tau positivity than PET amyloid positivity, suggesting a potential interaction between MDD and tau pathology. These findings highlight the importance of monitoring older drivers for emerging functional vulnerability associated with mood disorders and neurodegeneration at an early stage.This is a preview of subscription content, access via your institutionAccess optionsSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to the full article PDF.39,95 €Prices may be subject to local taxes which are calculated during checkoutFig. 1: Longitudinal trajectories of naturalistic driving behaviors by MDD and preclinical AD biomarker status.Fig. 2: The moderating effects of antidepressant among participants with MDD.Data availabilityDeidentified participant data from this study are available upon reasonable request to the corresponding author and with appropriate institutional approvals.ReferencesBabulal GM, Chen L, Trani JF, Brown DC, Carr DB, Ances BM, et al. Major depressive disorder and driving behavior among older adults. JAMA Netw Open. 2024;7:e2452038 https://doi.org/10.1001/jamanetworkopen.2024.52038Article PubMed PubMed Central Google Scholar Voelker RA. Driving impairment among older adults. JAMA. 2024;331:176–176.Article PubMed Google Scholar Kim S, Ulfarsson GF. Traffic safety in an aging society: analysis of older pedestrian crashes. J transportation Saf security. 2019;11:323–32.Article Google Scholar Mizenko AJ, Tefft BC, Arnold LS, Grabowski J. Older american drivers and traffic safety culture: a LongROAD study. (2014) (Technical Report). AAA Foundation for Traffic Safety. https://aaafoundation.org/older-american-drivers-traffic-safety-culture-longroad-study/Chihuri S, Mielenz TJ, DiMaggio CJ, Betz ME, DiGuiseppi C, Jones VC, et al. Driving cessation and health outcomes in older adults. J Am Geriatr Soc. 2016;64:332–41. https://doi.org/10.1111/jgs.13931Article PubMed PubMed Central Google Scholar Edwards JD, Lunsman M, Perkins M, Rebok GW, Roth DL. Driving cessation and health trajectories in older adults. J Gerontology Ser A: Biomed Sci Med Sci. 2009;64:1290–5.Article Google Scholar Chen C, Brown DC, Al-Hammadi N, Bayat S, Dickerson A, Vrkljan B, et al. Identifying major depressive disorder in older adults through naturalistic driving behaviors and machine learning. NPJ Digit Med. 2025;8:102 https://doi.org/10.1038/s41746-025-01500-wArticle PubMed PubMed Central Google Scholar Parhizi B, Kolady R, Vogel MT, Singh RK, Bekena S, Chokkalingam R, et al. Driving into diagnosis: leveraging high-resolution telematics and sensorimotor profiling to identify preclinical alzheimer’s disease. J Alzheimers Dis Rep. 2025;9:25424823251407543 https://doi.org/10.1177/25424823251407543Article PubMed PubMed Central Google Scholar Hill LL, Lauzon VL, Winbrock EL, Li G, Chihuri S, Lee KC. Depression, antidepressants and driving safety. Inj Epidemiol. 2017;4:10 https://doi.org/10.1186/s40621-017-0107-xArticle PubMed PubMed Central Google Scholar Miyata A, Iwamoto K, Kawano N, Aleksic B, Ando M, Ebe K, et al. Driving performance of stable outpatients with depression undergoing real-world treatment. Psychiatry Clin Neurosci. 2018;72:399–408. https://doi.org/10.1111/pcn.12648Article PubMed Google Scholar Brunnauer A, Herpich F, Zwanzger P, Laux G. Driving performance under treatment of most frequently prescribed drugs for mental disorders: a systematic review of patient studies. Int J Neuropsychopharmacol. 2021;24:679–93. https://doi.org/10.1093/ijnp/pyab031Article CAS PubMed PubMed Central Google Scholar Jack CR Jr, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, et al. Revised criteria for diagnosis and staging of alzheimer’s disease: alzheimer’s association workgroup. Alzheimers Dement. 2024;20:5143–69. https://doi.org/10.1002/alz.13859Article PubMed PubMed Central Google Scholar Barrett AE, Gumber C. Feeling older and driving less: the effect of age identity on older adults’ transition from driving. Innov Aging. 2019;3:igz004 https://doi.org/10.1093/geroni/igz004Article PubMed PubMed Central Google Scholar Huang G, Luster M, Karagol I, Park JW, Pitts BJ. Self-perception of driving abilities in older age: a systematic review. Transportation Res Part F: Traffic Psychol Behav. 2020;74:307–21. https://doi.org/10.1016/j.trf.2020.08.020Article Google Scholar Wood JM, Lacherez PF, Anstey KJ. Not all older adults have insight into their driving abilities: evidence from an on-road assessment and implications for policy. J Gerontology Ser A: Biomed Sci Med Sci. 2013;68:559–66.Article Google Scholar Babulal GM, Addison A, Ghoshal N, Stout SH, Vernon EK, Sellan M, et al. Development and interval testing of a naturalistic driving methodology to evaluate driving behavior in clinical research. F1000Research. 2016;5:1716.Article PubMed PubMed Central Google Scholar Babulal GM, Traub CM, Webb M, Stout SH, Addison A, Carr DB, et al. Creating a driving profile for older adults using GPS devices and naturalistic driving methodology. F1000Research. 2016;5:2376 https://doi.org/10.12688/f1000research.9608.2Article PubMed PubMed Central Google Scholar Blake M, Brown DC, Chen C, Al-Hammadi N, Casanova R, Zhu Y, et al. A combined naturalistic driving, clinical, and neurobehavioral data set for investigating aging and dementia. Sci Data. 2025;12:1209 https://doi.org/10.1038/s41597-025-05554-zArticle PubMed PubMed Central Google Scholar Babulal GM, Stout SH, Williams MM, Rajasekar G, Harmon A, Vivoda J, et al. Differences in driving outcomes among cognitively normal african american and caucasian older adults. J Racial Ethnic Health Disparities. 2020;7:269–80.Article Google Scholar Roe CM, Babulal GM, Head DM, Stout SH, Vernon EK, Ghoshal N, et al. Preclinical alzheimer’s disease and longitudinal driving decline. Alzheimer’s Dementia: Transl Res Clin Interventions. 2017;3:74–82.Google Scholar Farrell ME, Jiang S, Schultz AP, Properzi MJ, Price JC, Becker JA, et al. Defining the lowest threshold for amyloid-PET to predict future cognitive decline and amyloid accumulation. Neurology. 2021;96:e619–e631. https://doi.org/10.1212/WNL.0000000000011214Article CAS PubMed Google Scholar Su Y, Flores S, Wang G, Hornbeck RC, Speidel B, Joseph-Mathurin N, et al. Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies. Alzheimers Dement (Amst. 2019;11:180–90. https://doi.org/10.1016/j.dadm.2018.12.008Article PubMed PubMed Central Google Scholar Mishra S, Gordon BA, Su Y, Christensen J, Friedrichsen K, Jackson K, et al. AV-1451 PET imaging of tau pathology in preclinical alzheimer disease: defining a summary measure. Neuroimage. 2017;161:171–8. https://doi.org/10.1016/j.neuroimage.2017.07.050Article CAS PubMed PubMed Central Google Scholar Singh RK, Chen C, Bekena S, Brown DC, Taylor K, Blake M, et al. Harmonizing self-reported and free text medication data: a reproducible pipeline for gerontological research. BMC Med Inform Decis Mak. 2025;26:35.Article PubMed PubMed Central Google Scholar Aschenbrenner AJ, Gordon BA, Benzinger TLS, Morris JC, Hassenstab JJ. Influence of tau PET, amyloid PET, and hippocampal volume on cognition in alzheimer disease. Neurology. 2018;91:e859–e866. https://doi.org/10.1212/WNL.0000000000006075Article CAS PubMed PubMed Central Google Scholar Armitage SG. An analysis of certain psychological tests used for the evaluation of brain injury. Psychological Monogr. 1946;60:i–48.Article Google Scholar Grober E, Buschke H, Crystal H, Bang S, Dresner R. Screening for dementia by memory testing. Neurology. 1988;38:900–900.Article CAS PubMed Google Scholar Zhu Y, Singh RK, Bekena S, Brown DC, Chen C, Blake M, et al. Lost before forgetting: objective driving metrics track navigation deficits tied to preclinical alzheimer’s disease. Innov Aging. 2026;10:igag013.Article PubMed PubMed Central Google Scholar Babulal GM, Ghoshal N, Head D, Vernon EK, Holtzman DM, Benzinger T, et al. Mood changes in cognitively normal older adults are linked to alzheimer disease biomarker levels. Am J geriatric psychiatry. 2016;24:1095–104.Article Google Scholar Sierra-Fonseca JA, Gosselink KL. Tauopathy and neurodegeneration: a role for stress. Neurobiol Stress. 2018;9:105–12. https://doi.org/10.1016/j.ynstr.2018.08.009Article PubMed PubMed Central Google Scholar Arenaza-Urquijo EM, Przybelski SA, Machulda MM, Knopman DS, Lowe VJ, Mielke MM, et al. Better stress coping associated with lower tau in amyloid-positive cognitively unimpaired older adults. Neurology. 2020;94:e1571–e1579. https://doi.org/10.1212/WNL.0000000000008979Article PubMed PubMed Central Google Scholar Babulal GM, Roe CM, Stout SH, Rajasekar G, Wisch JK, Benzinger T, et al. Depression is associated with tau and not amyloid positron emission tomography in cognitively normal adults. J Alzheimers Dis. 2020;74:1045–55. https://doi.org/10.3233/JAD-191078Article PubMed PubMed Central Google Scholar Moriguchi S, Takahata K, Shimada H, Kubota M, Kitamura S, Kimura Y, et al. Excess tau PET ligand retention in elderly patients with major depressive disorder. Mol Psychiatry. 2021;26:5856–63. https://doi.org/10.1038/s41380-020-0766-9Article CAS PubMed Google Scholar Gatchel JR, Donovan NJ, Locascio JJ, Schultz AP, Becker JA, Chhatwal J, et al. Depressive symptoms and tau accumulation in the inferior temporal lobe and entorhinal cortex in cognitively normal older adults: a pilot study. J Alzheimers Dis. 2017;59:975–85. https://doi.org/10.3233/JAD-170001Article CAS PubMed PubMed Central Google Scholar Livingston G, Huntley J, Liu KY, Costafreda SG, Selbæk G, Alladi S, et al. Dementia prevention, intervention, and care: 2024 report of the lancet standing commission. Lancet. 2024;404:572–628.Article PubMed Google Scholar Invernizzi S, Simoes Loureiro I, Kandana Arachchige KG, Lefebvre L. Late-life depression, cognitive impairment, and relationship with alzheimer’s disease. Dement geriatric Cognit Disord. 2022;50:414–24.Article Google Scholar Gallagher D, Kiss A, Lanctot K, Herrmann N. Depression and risk of alzheimer dementia: a longitudinal analysis to determine predictors of increased risk among older adults with depression. Am J Geriatric Psychiatry. 2018;26:819–27.Article Google Scholar Brunnauer A, Laux G. Driving under the influence of antidepressants: a systematic review and update of the evidence of experimental and controlled clinical studies. Pharmacopsychiatry. 2017;50:173–81.Article CAS PubMed Google Scholar Sasada K, Iwamoto K, Kawano N, Kohmura K, Yamamoto M, Aleksic B, et al. Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers. Hum Psychopharmacology: Clin Exp. 2013;28:281–6.Article CAS Google Scholar Download referencesAcknowledgementsThis work was funded by the National Institute of Health (NIH) and National Institute on Aging (NIH/NIA) grants R01AG068183 (GMB), R01AG056466 (GMB), R01AG067428 (GMB).Author informationAuthors and AffiliationsDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USAYiqi Zhu, David C. Brown, Chen Chen, Ramkrishna K. Singh, Semere Bekena, Beau M. Ances & Ganesh M. BabulalSocial Work School, Adelphi University, Garden City, NY, USAYiqi Zhu & Eric J. LenzeDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USADavid B. CarrDepartment of Medicine, Washington University in School of Medicine, St. Louis, MO, USAJean-Francios TraniBrown School, Washington University in St Louis, St Louis, MO, USAJean-Francios TraniNational Conservatory of Arts and Crafts, 2 rue Conté, Paris, 75003, FranceJean-Francios TraniInstitute of Public Health, Washington University School of Medicine, St Louis, Missouri, USJean-Francios Trani & Ganesh M. BabulalDepartment of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South AfricaGanesh M. BabulalDepartments of Neurology and Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USAGanesh M. BabulalAuthorsYiqi ZhuView author publicationsSearch author on:PubMed Google ScholarDavid C. BrownView author publicationsSearch author on:PubMed Google ScholarChen ChenView author publicationsSearch author on:PubMed Google ScholarRamkrishna K. SinghView author publicationsSearch author on:PubMed Google ScholarSemere BekenaView author publicationsSearch author on:PubMed Google ScholarBeau M. AncesView author publicationsSearch author on:PubMed Google ScholarEric J. LenzeView author publicationsSearch author on:PubMed Google ScholarDavid B. CarrView author publicationsSearch author on:PubMed Google ScholarJean-Francios TraniView author publicationsSearch author on:PubMed Google ScholarGanesh M. BabulalView author publicationsSearch author on:PubMed Google ScholarContributionsGMB devised the study. YZ and GMB analyzed the data and generated figures. YZ and GMB drafted the manuscript. All authors contributed to the interpretation of the data and reviewed the manuscript.Corresponding authorCorrespondence to Ganesh M. Babulal.Ethics declarationsCompeting interestsThe authors report no conflicts with any product mentioned or concept discussed in this article.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Rights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this article