Higher FT4 or TSH below the normal range are associated with increased risk of dementia: a meta-analysis of 11 studies

Wu, Yue; Pei, Yuqing; Wang, Fei; Xu, Danfei; Cui, Wei

doi:10.1038/srep31975

Cited by 23 publications

(37 citation statements)

References 58 publications

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“…Lack of TH in utero and in early life causes severe cognitive impairment, with extensive white matter pathology (Rosman, 1972). In later life, hyperthyroidism has been often associated with cognitive decline (Akintola et al, 2015;Chaker et al, 2018;Chaker et al, 2016;Moon, 2016;Moon et al, 2014;Rieben et al, 2016;Tan and Vasan, 2009;Wu et al, 2016;Yeap et al,2012). A recent PubMed search using "(thyroid or thyroxine) and (Alzheimer's or dementia)" returns >600 published papers.…”

Section: Discussionmentioning

confidence: 99%

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels

Nelson

Gal

Wang

et al. 2019

Neurobiology of Disease

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TDP-43 proteinopathy is very common among the elderly (affecting at least 25% in individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n=136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic pathology in the hippocampal formation. Overall, 46.4% of the cases were positive for TDP-43 intracellular inclusions, which is consistent with results in other prior community-based cohorts. The pathologies were correlated with hippocampal sclerosis of aging (HS-Aging) linked genotypes. We also assayed brain parenchymal thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels. In cases with SLCO1A2/IAPP or ABCC9 risk associated genotypes, the T3/T4 ratio tended to be reduced (p=0.051 using 2-tailed statistical test), and in cases with low T3/T4 ratios (bottom quintile), there was a higher likelihood of HS-Aging pathology (p=0.025 using 2-tailed statistical test). This is intriguing because the SLCO1A2/IAPP and ABCC9 risk associated genotypes have been associated with altered expression of the astrocytic thyroid hormone receptor (product of the nearby gene SLCO1C1). These data indicate that dysregulation of thyroid hormone signaling may play a role in TDP-43 proteinopathy.

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Section: Discussionmentioning

confidence: 99%

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels

Nelson

Gal

Wang

et al. 2019

Neurobiology of Disease

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“…A routine screening test, free T3, free T4, and TSH were assessed in the cases and 105 control subjects with mean age - 62 years, which revealed subclinical hyperthyroidism and AD to have a consistent association [ 24 ]. A meta-analysis of 11 studies by Yue Wu et al with a total of 24,952 participants, established relationships between dementia and the per SD increment of free thyroxine (FT4) (RR = 1.08, 95% CI 1.00-1.17) and thyroid-stimulating hormone (TSH) (fixed RR = 0.91, 95% CI 0.84-0.99) [ 25 ]. An increased risk of dementia (fixed RR = 1.60, 95% CI 1.27-2.00) was found with TSH levels below the normal range and with higher FT4 levels.…”

Section: Reviewmentioning

confidence: 99%

“…An increased risk of dementia (fixed RR = 1.60, 95% CI 1.27-2.00) was found with TSH levels below the normal range and with higher FT4 levels. But low or high categories of TSH in men did not show any association with the risk of dementia [ 25 ].…”

Section: Reviewmentioning

confidence: 99%

Is Hyperthyroidism a Possible Etiology of Early Onset Dementia?

Mathew

Jose

Elshaikh

et al. 2020

Cureus

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Dementia, a disabling syndrome of the elderly characterized by the decline in memory and cognition, is increasing in incidence and affects not only the individual but also their family and close ones. Hyperthyroidism can mimic many other diseases and untreated hyperthyroidism can lead to adverse problems of various systems including the heart, bones, muscles, menstrual cycle, and fertility. In this article, we have tried to evaluate the association between hyperthyroidism and dementia, as well as the impact of hyperthyroidism management in the treatment and prevention of dementia. Studies available in the PubMed database have been used, excluding animal studies and including studies of adults above the age of 50. The analysis of studies reveals that thyroid dysfunction can lead to cognitive impairment. It has not been able to prove that hyperthyroidism can lead to an earlier onset of dementia. But subclinical hyperthyroidism, thyroid-stimulating hormone (TSH) levels below the normal range, and high free thyroxine (T4) levels increase the risk of dementia among the elderly. The possible mechanisms involved in this association have also been discussed. Thus, we concluded that it is essential to detect and manage hyperthyroidism at an earlier stage since hyperthyroidism increases the risk of dementia. The possibility of using antithyroid treatment in euthyroid dementia is yet to be studied extensively.

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“…In the present study, we grouped all dementia diagnoses together to be able to have enough statistical power for the analyses. However, this is also performed in other studies as well [4, 8, 10], and in the clinical situation this is more relevant for doctors as well as patients. As dementia is a cluster of disorders developing over many years, patients may die as a result of other causes before getting a dementia diagnosis, i.e., because of a competing risk, which could affect the results.…”

Section: Conclusion and Limitationsmentioning

confidence: 94%

“…A recent study found hypothyroidism to be associated with cerebrovascular diseases but not with AD pathology [6]. Higher levels of free thyroxin have repeatedly been shown to be associated with incident dementia [7, 8]. Animal models have shown hypothyroidism to induce the amyloidogenic pathway of amyloid precursor protein processing in the hippocampus [9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Levothyroxine Treatment on Incident Dementia in Adults with Atrial Fibrillation and Hypothyroidism

et al. 2018

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Background and Objective The possible adverse or positive effects of levothyroxine treatment among patients with atrial fibrillation have been debated. Atrial fibrillation, levothyroxine treatment, and dementia are common among older adults, yet little is known about the effects of levothyroxine on the development of dementia. Methods The study population included all adults ( n = 12,057) aged ≥ 45 years with a diagnosis of atrial fibrillation at 75 primary care centers in Sweden during 2001–2007 without an earlier recorded dementia diagnosis. Patients with a diagnosis of hypothyroidism and levothyroxine prescription ( n = 756; 180 men and 576 women), or with a prescription without this diagnosis ( n = 415, 100 men and 315 women), were compared to patients without a diagnosis and prescription ( n = 10,886). Cox regression was performed, with hazard ratios and 95% confidence intervals, with outcome defined as dementia of all causes until 31 December, 2010. Results During a mean 5.7 years (standard deviation 2.4 years) of follow-up, a total of 749 patients with atrial fibrillation (6.2%) were diagnosed with dementia. Women with hypothyroidism and a levothyroxine prescription showed lower hazard ratios (0.61; 0.41–0.90) in adjusted Cox regression models (age, socioeconomic factors, co-morbidity, and warfarin treatment). Levothyroxine prescription without hypothyroidism was non-significant. Conclusions We found that women with atrial fibrillation with levothyroxine treatment and hypothyroidism have a lower risk of incident dementia than women with atrial fibrillation without levothyroxine treatment and no hypothyroidism. The results should be confirmed in larger studies. Electronic supplementary material The online version of this article (10.1007/s40261-018-0740-3) contains supplementary material, which is available to authorized users.

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Higher FT4 or TSH below the normal range are associated with increased risk of dementia: a meta-analysis of 11 studies

Cited by 23 publications

References 58 publications

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels

Is Hyperthyroidism a Possible Etiology of Early Onset Dementia?

Effect of Levothyroxine Treatment on Incident Dementia in Adults with Atrial Fibrillation and Hypothyroidism

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