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Growing evidence indicates that nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    )\u00a0interacts with the circadian system through multiple molecular pathways and that NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0levels decline with dementia. In this review, we synthesize current evidence on the bidirectional relationship between NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0metabolism and circadian regulation in several dementia disorders, emphasizing the key circadian pathways, the nicotinamide phosphoribosyltransferase\u2010mediated salvage synthesis, the NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/sirtuins\u2010dependent signaling, and the consumption of NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0by PARP1 and CD38. Finally, we also examine pharmacological and lifestyle strategies that target NAD\n                    <jats:sup>+<\/jats:sup>\n                    , including NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0precursors, modulators of NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0biosynthetic and depleting enzymes, timed light and activity exposure, structured exercise programs, and dietary interventions. Overall, we focus on the bidirectional interplay between NAD\n                    <jats:sup>+<\/jats:sup>\n                    metabolism and circadian rhythm regulation in dementia, with particular emphasis on how this interaction influences sleep and cognitive phenotypes across different dementia subtypes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration<\/jats:bold>\n                    : ClinicalTrials.gov identifier: NCT05040321, NCT04430517, NCT06971224, NCT05500170, NCT04070378\n                  <\/jats:p>","DOI":"10.1002\/alz.71360","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:08:18Z","timestamp":1777619298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NAD\n                    <sup>+<\/sup>\n                    \u2012circadian rhythm coupling in dementia"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-7652","authenticated-orcid":false,"given":"Shi\u2010qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital, Dalian Medical University  Dalian China"},{"name":"Department of Clinical Molecular Biology University of Oslo and Akershus University Hospital  L\u00f8renskog Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-2397","authenticated-orcid":false,"given":"Jiyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Convergence Research of Neurological Disorders Ajou University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3777-5654","authenticated-orcid":false,"given":"Jun\u2010ping","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology University of Oslo and Akershus University Hospital  L\u00f8renskog Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-7117","authenticated-orcid":false,"given":"Rune","family":"Enger","sequence":"additional","affiliation":[{"name":"Letten Centre and GliaLab Division of Anatomy Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo  Oslo Norway"},{"name":"Department of Neurosurgery Oslo University Hospital, Rikshospitalet  Oslo Norway"},{"name":"K. 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