Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study

Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study | medRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study Shu Sun , View ORCID Profile Naoto Kajitani , Kazuhiro Yoshiura , Manabu Makinodan , View ORCID Profile Minoru Takebayashi doi: https://doi.org/10.64898/2026.03.17.26348449 Shu Sun 1 Department of Psychiatry and Neuroscience, Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University , Kumamoto, Japan 2 Department of Neuropsychiatry, Kumamoto University , Kumamoto, Japan BM Find this author on Google Scholar Find this author on PubMed Search for this author on this site Naoto Kajitani 1 Department of Psychiatry and Neuroscience, Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University , Kumamoto, Japan PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Naoto Kajitani For correspondence: nkajitani{at}kumamoto-u.ac.jp mtakebayashi{at}kumamoto-u.ac.jp Kazuhiro Yoshiura 3 Department of Frailty Research, Center for Gerontology and Social Science, Research Institute, National Center for Geriatrics and Gerontology , Obu, Japan PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Manabu Makinodan 2 Department of Neuropsychiatry, Kumamoto University , Kumamoto, Japan MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Minoru Takebayashi 1 Department of Psychiatry and Neuroscience, Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University , Kumamoto, Japan MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Minoru Takebayashi For correspondence: nkajitani{at}kumamoto-u.ac.jp mtakebayashi{at}kumamoto-u.ac.jp Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Aim To examine the determinants of serum autotaxin (ATX) levels in community-dwelling older adults, focusing specifically on endogenous adrenal steroids, and to investigate the cross-sectional and longitudinal associations between serum ATX levels, cognitive function, and depressive symptoms. Methods Data were obtained from community-dwelling older adults aged 65 years and older in Arao City, Japan (baseline: 1,488; follow-up: 730). Serum ATX and dehydroepiandrosterone sulfate (DHEAS) levels were measured, and cognitive function and depressive symptoms were assessed using the Mini–Mental State Examination (MMSE) and Geriatric Depression Scale (GDS). Multiple linear regression models were applied to examine any cross-sectional associations among serum ATX levels, adrenal steroids, and MMSE/GDS scores. Longitudinal analyses assessed whether baseline serum ATX levels predicted 6-year changes in MMSE and GDS scores, with additional sex-stratified analyses and propensity score matching conducted to address any potential follow-up bias. Results After adjusting for age and sex, DHEAS levels were inversely associated with ATX levels. Cross-sectional analyses identified no association between serum ATX levels and MMSE/GDS scores. However, longitudinal analyses demonstrated significant associations between baseline serum ATX levels and changes in MMSE scores, particularly among women, and remained significant after multivariate and propensity score–matched analyses. Conclusion This study provides epidemiological evidence of an inverse association between DHEAS and ATX, indicating a potential link between adrenal endocrine function and ATX regulation. In older women, baseline serum ATX levels were associated with inter-individual variability in subsequent cognitive trajectories, indicating a potential role for ATX in age-related cognitive changes. Competing Interest Statement MT received collaborative research funding from TOSOH Corporation, which provided technical support for the measurement of serum ATX and DHEAS levels. The funder had no role in the study design, data analysis, data interpretation, or manuscript preparation. All other authors declare no competing interests. Funding Statement This study was supported in part by the Japan Agency for Medical Research and Development (AMED; JP25dk0207053), and by a collaborative research grant from TOSOH Corporation. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for the baseline and follow-up surveys was obtained from the Ethics Committee of Kumamoto University, Kumamoto, Japan (Approval No. GENOME-333). Written informed consent was obtained from all participants or their legally authorized representatives. The present study analyzed stored biological samples and associated data as secondary research, which was separately approved by the same Ethics Committee (Approval No. RINRI-2915). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted March 19, 2026. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study Shu Sun , Naoto Kajitani , Kazuhiro Yoshiura , Manabu Makinodan , Minoru Takebayashi medRxiv 2026.03.17.26348449; doi: https://doi.org/10.64898/2026.03.17.26348449 Share This Article: Copy Citation Tools Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study Shu Sun , Naoto Kajitani , Kazuhiro Yoshiura , Manabu Makinodan , Minoru Takebayashi medRxiv 2026.03.17.26348449; doi: https://doi.org/10.64898/2026.03.17.26348449 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Psychiatry and Clinical Psychology Subject Areas All Articles Addiction Medicine (638) Allergy and Immunology (917) Anesthesia (350) Cardiovascular Medicine (5005) Dentistry and Oral Medicine (496) Dermatology (428) Emergency Medicine (676) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1691) Epidemiology (16263) Forensic Medicine (36) Gastroenterology (1241) Genetic and Genomic Medicine (7278) Geriatric Medicine (751) Health Economics (1093) Health Informatics (5288) Health Policy (1467) Health Systems and Quality Improvement (1832) Hematology (599) HIV/AIDS (1381) Infectious Diseases (except HIV/AIDS) (16490) Intensive Care and Critical Care Medicine (1203) Medical Education (700) Medical Ethics (156) Nephrology (752) Neurology (7596) Nursing (377) Nutrition (1130) Obstetrics and Gynecology (1296) Occupational and Environmental Health (1040) Oncology (3745) Ophthalmology (1093) Orthopedics (409) Otolaryngology (465) Pain Medicine (501) Palliative Medicine (143) Pathology (721) Pediatrics (1858) Pharmacology and Therapeutics (755) Primary Care Research (786) Psychiatry and Clinical Psychology (6130) Public and Global Health (9992) Radiology and Imaging (2530) Rehabilitation Medicine and Physical Therapy (1519) Respiratory Medicine (1269) Rheumatology (661) Sexual and Reproductive Health (804) Sports Medicine (597) Surgery (803) Toxicology (109) Transplantation (319) Urology (308)

Related documents

• Female vulnerability to microvascular transport dysfunction emerges early across the Alzheimer's disease continuum#684663
• Age-Related changes in cognition, plasma levels of brain-derived Neurotrophic factor and selected indices of inflammation in adults at different decades of life#390199
• Salivary Dysbiosis Aligns with an Olfactory–Cognitive Phenotype in Aging#422504
• Effects of a 6-months Fiber- and Polyphenol-rich Diet on Brain Inflammatory Processes in Perimenopausal Women Living With Overweight or Obesity#1170318
• Machine-Learning Assessment of the Predictive Value of Inflammatory Biomarkers for Cognitive Impairment in an Older Hispanic Adult Cohort#1013970