Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease

Osch, L.A.D.M. van; Hogervorst, Eef; Combrinck, Marc; Smith, A.D.

doi:10.1212/01.wnl.0000128134.84230.9f

Cited by 129 publications

(81 citation statements)

References 33 publications

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“…However, we demonstrate that elderly subjects with cognitive impairment have lower T3, T4 and TSH hormone levels, and higher systolic BP, compared to elderly healthy subjects. This result was in agreement with van Osch et al, who reported that Alzheimer's disease patients had significantly lower levels of TSH [26]. Lower levels of TSH were associated with a more than two-fold increased risk of Alzheimer's disease, independently of other risk factors.…”

Section: Discussionsupporting

confidence: 92%

Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment

Niculescu¹,

Toma²,

Ianăş

et al. 2012

Open Life Sciences

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The association of cholesteryl ester transfer protein (CETP) and apolipoprotein E (APOE) gene polymorphisms with mild cognitive impairment (MCI) is under debate. Our aim was to evaluate the relationship between APOE and CETP genotypes with healthy ageing. We analysed 267 elderly subjects (55 to 80+ years), 163 with MCI and 104 healthy, and 50 healthy control subjects (35 to 55 years) from a Romanian population. Biochemical parameters and thyroid hormones were assayed in plasma. APOE and CETP TaqIB gene polymorphisms were determined. Elderly subjects had higher frequency of ɛ3/ɛ2 genotype (14.6% vs. 4%, P<0.001) than controls. Elderly subjects with MCI had lower high density lipoproteins (HDL) cholesterol (P=0.031), apoA-I (P=0.018), T3 (P=0.002), T4 (P=0.028) and TSH (P=0.001) hormone levels, higher systolic blood pressure (P=0.005), lower frequency of CETP B2 allele than the age-matched subjects. Healthy elderly subjects had CETP B2 allele associated with higher plasma apoA-I (P=0.021), lower circulating collagen (P=0.001) levels, and an increased frequency of the combined APOE ɛ2- CETP B2 genotype (18.3%) relative to MCI elderly subjects (7.6%, P=0.011). Healthy elderly subjects are characterized by higher HDL cholesterol, apoA-I levels and higher frequency of the combined APOE ɛ2 and CETP B2 alleles, indicating this pattern as representative for healthy ageing.

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Section: Discussionsupporting

confidence: 92%

Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment

Niculescu¹,

Toma²,

Ianăş

et al. 2012

Open Life Sciences

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“…There are conflicting data on the risk of dementia in elderly patients with SHyper, and the mechanism is unclarified [54,55,56,57,58]. A recent systematic review provided evidence for an association between SHyper or low serum TSH within the reference range and cognitive impairment or dementia [59].…”

Section: Risks Associated With Persistent and Untreated Endo Subclinimentioning

confidence: 99%

The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism

Biondi¹,

Bartalena²,

Cooper³

et al. 2015

Eur Thyroid J

244

157

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Endogenous subclinical hyperthyroidism (SHyper) is caused by Graves' disease, autonomously functioning thyroid nodules and multinodular goitre. Its diagnosis is based on a persistently subnormal serum thyroid-stimulating hormone (TSH) level with free thyroid hormone levels within their respective reference intervals. In 2014 the European Thyroid Association Executive Committee, given the controversies regarding the treatment of Endo SHyper, formed a task force to develop clinical practice guidelines based on the principles of evidence-based medicine. The task force recognized that recent meta-analyses, including those based on large prospective cohort studies, indicate that SHyper is associated with increased risk of coronary heart disease mortality, incident atrial fibrillation, heart failure, fractures and excess mortality in patients with serum TSH levels <0.1 mIU/l (grade 2 SHyper). Therefore, despite the absence of randomized prospective trials, there is evidence that treatment is indicated in patients older than 65 years with grade 2 SHyper to potentially avoid these serious cardiovascular events, fractures and the risk of progression to overt hyperthyroidism. Treatment could be considered in patients older than 65 years with TSH levels 0.1-0.39 mIU/l (grade 1 SHyper) because of their increased risk of atrial fibrillation, and might also be reasonable in younger (<65 years) symptomatic patients with grade 2 SHyper because of the risk of progression, especially in the presence of symptoms and/or underlying risk factors or co-morbidity. Finally, the task force concluded that there are no data to support treating SHyper in younger asymptomatic patients with grade 1 SHyper. These patients should be followed without treatment due to the low risk of progression to overt hyperthyroidism and the weaker evidence for adverse health outcomes.

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“…Subclinical as well as clinical thyroid diseases are shown to be connected with cardiovascular disease and vascular risk factors with accumulating epidemiologic evidence that vascular risk factors increase the risk of AD, indicating a connection between thyroid function and AD [9,[11][12][13][14] . It could be that T4 may generate oxidative stress and damage neurons [15] .…”

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confidence: 99%

A Prospective Study on the Development of Alzheimer’s Disease with Regard to Thyroid-Stimulating Hormone and Homocysteine

Annerbo

Kivipelto²,

Lökk³

2009

Dement Geriatr Cogn Disord

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Background/Aim: The combination of elevated total homocysteine (tHcy) levels and low levels of thyroid-stimulating hormone (TSH) are linked to Alzheimer’s disease (AD) in some studies, although the evidence is mixed. Our objective was to prospectively investigate the association between tHcy and TSH and the subsequent development of AD. Methods: A subsample of 200 nondemented subjects was taken from the Kungsholmen Project, a population-based study among people ≥75 years. Information about tHcy and TSH levels were taken from the baseline investigation of the Kungsholmen Project study. Results: Increased tHcy levels were related to an elevated risk of AD (n = 61) after a mean follow-up time of 6.7 years. People with high tHcy (the 3rd tertile) had more than twice as high a risk of developing AD than those with low tHcy, even after adjusting for age, sex, education, ApoE status, MMSE score and laboratory parameters. tHcy was negatively correlated with TSH (p = 0.02). There was neither an influence of TSH nor an interaction between tHcy and TSH in the development of AD. Conclusions: These results suggest that homocysteine, but not TSH, is involved in the development of AD. The connection between elevated tHcy and low TSH levels needs to be studied further.

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Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease

Abstract: Lowered TSH within the normal range is a risk factor for AD, independent of several cerebrovascular risk factors and confounding variables.

Cited by 129 publications

References 33 publications

Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment

Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment

The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism

A Prospective Study on the Development of Alzheimer’s Disease with Regard to Thyroid-Stimulating Hormone and Homocysteine

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