Abstract
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 (<47 years), typical (48–59), and late (>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–Whitney 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-Ɛ4 (correlation: 0.44, 0.24, 0.60; odds ratio: 1.09, 1.05–1.14). However, an early age of hypothyroidism onset and the presence of the APOE-Ɛ4 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.
Highlights
TableThyroid antibody summaries by ditions of the Creative Commons Atatgael oofrAbDioolongseictaglrfoaucpto. rs and co-existing medical conditions.egard to jurisdictional blished maps and institutions.Adults with Down syntdribruotimoEnae(rCl(CyDBSY)) lhicaenvsee (ahtntp:e//scrpeae-cTiyaplliycahligThhryirsokidforddysefvuenlLocatptieoinng, Ainlczl-uding congenital, subclinica heimer disease (AD), with ontivseectomamt loenas.sotrgt/wliceonsdese/cbya/d4.0e/s). earliecrotnhdanitiionntsh[e6g],einsearavleproypcuolmatmioonn medical pco-morbidity in in [1,2]
The primary limitations of this study include: (1) the retrospective nature of the study design; (2) the possible measurement error associated with ages of AD onset and hypothyroidism onset; and (3) the degree of missingness especially involving the thyroid autoantibody panels
A7moofn8g patients mographics, hypothyroidism variables toantibodies, and APOE genotypes we Citation: Lai, F.; Mercaldo, N.D.; Wang, C.M.; Hersch, M.S.; Hersch, man and partial Spearman correlations quantify the association between ages o
Summary
IRB approval for a medical records review was obtained from Massachusetts General Hospital. A total of 232 patients were identified who had been diagnosed with possible or probable AD, based on the criteria developed by the AAMR-IASSID Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Developmental Disability [26]. Patients were classified into two groups of premorbid level of intellectual disability (LID) based on IQ scores or functional ability: (1) mild/moderate LID: IQ between 40 and 70, ability to perform most activities of daily living (ADL), and reasonable language skills; (2) severe/profound LID: IQ < 40, needing at least some assistance in ADLs, with limited language skills
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
