{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:38:12Z","timestamp":1768207092565,"version":"3.49.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cognitive stimulation therapy (CST) and its maintenance phase (MCST) can benefit dementia. We evaluated treatment\u2013effect heterogeneity by euthyroid versus subclinical hypothyroidism\/hyperthyroidism during the 16-week maintenance period following CST.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective single-center cohort embedded in routine CST to MCST. All entrants to 7-week CST were assessed at baseline\/8\/16\/24\u2009weeks. Sixteen-week MCST occurred per usual care. Baseline TSH\/FT4\/FT3 are classified as euthyroid, subclinical hypothyroidism (SCH), or hyperthyroidism (SHyper). Co-primary outcomes were 24-week Montreal Cognitive Assessment (MoCA) and Zarit changes. We used doubly robust inverse-probability-of-treatment weighting combined with linear mixed-effects models to test MCST\u00d7thyroid interactions and controlled for multiple testing with a false-discovery-rate approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of a total of 242 participants screened, 200 were enrolled, and 174 (87.0%) completed the 24-week study session. MCST continuation was 112 of 200 (56.0%) participants. Thyroid status was available for 196 participants, with 137 (69.9%) being euthyroid, 45 (23.0%) being SCH, and 14 (7.1%) being SHyper. The MCST\u00d7thyroid interaction for 24-week MoCA change was \u22120.9 (95% CI \u22121.6 to \u22120.2;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012;\n                      <jats:italic>q<\/jats:italic>\n                      \u2009=\u20090.012); MCST improved MoCA by +1.4 (95% CI +0.6 to +2.2) in euthyroid versus +0.5 (\u22120.4 to +1.3) in subclinical dysfunction. For Zarit, the interaction was +2.1 (95% CI +0.5 to +3.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011;\n                      <jats:italic>q<\/jats:italic>\n                      \u2009=\u20090.012), with larger burden reduction in euthyroid (\u22123.4; 95% CI \u22125.3 to \u22121.5) than subclinical dysfunction (\u22121.3; \u22123.1 to +0.4). Secondary outcomes favored MCST but were attenuated at higher TSH levels (spline\n                      <jats:italic>\u03c7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20098.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030). Agitation occurred in 3 of 200 participants (1.5%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MCST improved cognition and reduced caregiver burden over 24\u2009weeks, with smaller benefits in subclinical thyroid dysfunction. Thyroid-aware personalization may better target maintenance cognitive interventions in late-life dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1710962","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:41:53Z","timestamp":1768196513000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thyroid function status and heterogeneity of efficacy of maintenance cognitive stimulation in late-life dementia: a stratified observational study of subclinical hypothyroidism\/hyperthyroidism"],"prefix":"10.3389","volume":"16","author":[{"given":"Ruili","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4324\/9781315209043-6","article-title":"Cognitive 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management and support for people living with dementia and their carers","year":"2018"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1089\/thy.2014.0028","article-title":"Guidelines for the treatment of hypothyroidism: prepared by the American thyroid association task force on thyroid hormone replacement","volume":"24","author":"Jonklaas","year":"2014","journal-title":"Thyroid"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1089\/thy.2016.0229","article-title":"2016 American Thyroid Association guidelines for diagnosis and Management of Hyperthyroidism and Other Causes of thyrotoxicosis","volume":"26","author":"Ross","year":"2016","journal-title":"Thyroid"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1056\/NEJMoa1603825","article-title":"Thyroid hormone therapy for older adults with subclinical hypothyroidism","volume":"376","author":"Stott","year":"2017","journal-title":"N Engl J Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.2018.13770","article-title":"Association of Thyroid Hormone Therapy with Quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: a systematic review and Meta-analysis","volume":"320","author":"Feller","year":"2018","journal-title":"JAMA"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.2147\/CIA.S61849","article-title":"Guidelines for adapting cognitive stimulation therapy to other cultures","volume":"9","author":"Aguirre","year":"2014","journal-title":"Clin Interv Aging"}],"container-title":["Frontiers in 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