{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:54:12Z","timestamp":1790351652141,"version":"4.1.0"},"reference-count":50,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Shenzhen Science and Technology Program","award":["JCYJ20220818102810022"],"award-info":[{"award-number":["JCYJ20220818102810022"]}]},{"name":"Key Program for Clinical Research at Peking University Shenzhen Hospital","award":["LCYJZD2022006"],"award-info":[{"award-number":["LCYJZD2022006"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,10,13]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>With the global ageing population accelerating, the prevalence of Alzheimer\u2019s disease (AD) continues to rise annually. However, the underlying mechanisms of AD remain unclear, and effective treatments are still lacking. Apolipoprotein E (ApoE) gene polymorphism and dietary habits are critical risk factors for AD. Time-restricted feeding (TRF), an intermittent fasting strategy that limits the daily window of food intake while maintaining nutritional balance, has garnered significant attention in recent years for its potential to improve cognitive dysfunction. This study aims to investigate the effect of TRF on cognitive improvement in AD patients within the context of genetic background and to explore the role of ApoE polymorphism in these mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This single-centre, prospective, randomised, open-label, blinded-endpoint trial will recruit 160 patients with mild to moderate cognitive impairment due to AD from Peking University Shenzhen Hospital. Participants will be stratified based on ApoE genotype into ApoE4 non-carriers and ApoE4 carriers, then randomly assigned to either a TRF intervention group or a normal control group for a 24-month intervention period. The primary outcomes are changes in the Minimum Mental State Examination scale score, Montreal Cognitive Assessment scale score and Clinical Dementia Rating-Sum of Boxes scale score. Key secondary outcomes include the Activities of Daily Living scale score, blood AD biomarkers, lipid levels, ketone body levels and cerebral glutamate levels. Follow-up assessments will be conducted at baseline, 6, 12, 18 and 24 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval for this study was obtained from the Research Ethics Committee of Peking University Shenzhen Hospital (Ethics No. 2024\u2013151). Written informed consent will be obtained from all participants before the commencement of the trial. The findings will be disseminated through peer-reviewed publications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2400092653<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-099591","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:45:18Z","timestamp":1762753518000},"page":"e099591","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of time-restricted feeding on cognitive dysfunction in Alzheimer\u2019s disease and the role of ApoE polymorphism: protocol for a randomised controlled trial"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7553-3862","authenticated-orcid":false,"given":"Jiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Northwest A&F University, Yangling, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"},{"name":"Department of Neurology, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhen","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Northwest A&F University, Yangling, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics Chinese Academy of Sciences, Chaoyang, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Northwest A&F University, Yangling, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"2025120413262288000_15.11.e099591.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"2025120413262288000_15.11.e099591.2","unstructured":"Europe . 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