{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T12:13:25Z","timestamp":1778242405492,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Adults with Down syndrome (DS) have an exceptionally high frequency of Alzheimer disease (AD) with a wide variability in onset, from 40 to 70 years of age. Equally prevalent in DS is hypothyroidism. In this study, we sought to quantify the relationship between the two. A total of 232 adults with DS and AD were stratified into three AD onset age groups: early (&lt;47 years), typical (48\u201359), and late (&gt;59). Among patients with available data, differences in the distributions of demographics, hypothyroidism variables (presence, age of onset), thyroid function tests, thyroid autoantibodies, and APOE genotypes were assessed (e.g., chi-squared, Mann\u2013Whitney tests). Spearman and partial Spearman correlations and ordinal logistic regression models were constructed to quantify the association between ages of AD and hypothyroidism onset with and without covariate adjustments. We observed a positive association between the ages of AD and hypothyroidism onset after accounting for APOE-\u01904 (correlation: 0.44, 0.24, 0.60; odds ratio: 1.09, 1.05\u20131.14). However, an early age of hypothyroidism onset and the presence of the APOE-\u01904 allele were independently associated with the early age of AD onset. Similar findings were observed when accounting for other factors. Our study provides evidence for the importance of hypothyroidism and associated pathological mechanisms for risk of AD in DS.<\/jats:p>","DOI":"10.3390\/brainsci11091223","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T21:38:12Z","timestamp":1631828292000},"page":"1223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome"],"prefix":"10.3390","volume":"11","author":[{"given":"Florence","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Massachusetts General Hospital, Charlestown, MA 02129, USA"},{"name":"McLean Hospital, Belmont, MA 02478, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1658-6598","authenticated-orcid":false,"given":"Nathaniel D.","family":"Mercaldo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Massachusetts General Hospital, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra M.","family":"Wang","sequence":"additional","affiliation":[{"name":"Harvard College, Harvard University, Cambridge, MA 02138, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micaela S.","family":"Hersch","sequence":"additional","affiliation":[{"name":"School of Nursing, Simmons University, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovi G.","family":"Hersch","sequence":"additional","affiliation":[{"name":"College of Arts & Sciences, Boston University, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herminia Diana","family":"Rosas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Massachusetts General Hospital, Charlestown, MA 02129, USA"},{"name":"McLean Hospital, Belmont, MA 02478, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1001\/archneur.1989.00520440031017","article-title":"A Prospective Study of Alzheimer Disease in Down Syndrome","volume":"46","author":"Lai","year":"1989","journal-title":"Arch. 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