Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome

Topic: Amyloid, tau and blood-test diagnosis

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 ( 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.

@article{lai2021-34573243,
  author  = {Lai, F. and Mercaldo, N. D. and Wang, C. M. and Hersch, M. S. and Hersch, G. G. and Rosas, H. D.},
  title   = {{Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome}},
  journal = {Brain sciences},
  year    = {2021},
  doi     = {10.3390/brainsci11091223},
  pmid    = {34573243},
  url     = {https://doi.org/10.3390/brainsci11091223}
}

Key findings

• 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.

Why it matters

Among 232 adults with Down syndrome and Alzheimer disease, later age of hypothyroidism onset was associated with later age of Alzheimer disease onset, while early hypothyroidism onset and the APOE-Ɛ4 allele were each linked to earlier Alzheimer onset. This is an association study and does not show that treating hypothyroidism prevents or delays Alzheimer's disease.

Study details

• Participants232
• Evidence strengthLow

Read the original

• DOI: 10.3390/brainsci11091223
• PubMed: 34573243
• Original source →
• Free full text: Brain Sciences →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Prevalence of Aging, Dementia, and Multimorbidity in Older Adults With Down Syndrome JAMA neurology · 2018-11-01 · usefulness score 61/100 · Down syndrome and Alzheimer's
• Thyroid function and the risk of dementia: The Rotterdam Study Neurology · 2016-09-16 · usefulness score 60/100 · Long-term cohort studies
• Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study Clinical endocrinology · 2000-12-01 · usefulness score 55/100 · Long-term cohort studies
• Cognitive deficits and associated neurological complications in individuals with Down's syndrome The Lancet. Neurology · 2010-06-01 · usefulness score 53/100 · Getting a diagnosis
• A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome Journal of intellectual disability research : JIDR · 2017-06-29 · usefulness score 53/100 · Brain tissue and pathology
• A prospective study of Alzheimer disease in Down syndrome Archives of neurology · 1989-08-01 · usefulness score 49/100 · How common it is
• The pathological association between Down syndrome and Alzheimer disease Mechanisms of ageing and development · 1988-05-01 · usefulness score 44/100 · Down syndrome and Alzheimer's
• Relation between apolipoprotein E genotype, hepatitis B virus status, and thyroid status in a sample of older persons with Down syndrome American journal of medical genetics. Part A · 2003-07-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• Autoimmune thyroiditis associated with mild "subclinical" hypothyroidism in adults with Down syndrome: a comparison of patients with and without manifestations of Alzheimer disease American journal of medical genetics · 1990-06-01 · usefulness score 35/100 · Down syndrome and Alzheimer's

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• State-of-the-art therapy for Down syndrome Developmental medicine and child neurology · 2023-01-24 · usefulness score 42/100 · Down syndrome and Alzheimer's

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Also tagged “down”

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• Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations The American journal of pathology · 2000-07-01 · usefulness score 52/100 · Genetics
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