Hypothyroidism and Risk of Mild Cognitive Impairment in Elderly Persons

Parsaik, Ajay K.; Singh, Balwinder; Roberts, Rosebud O.; Pankratz, Shane; Edwards, Kelly K.; Geda, Yonas E.; Gharib, Hossein; Boeve, Bradley F.; Knopman, David S.; Petersen, Ronald C.

doi:10.1001/jamaneurol.2013.5402

Cited by 59 publications

(37 citation statements)

References 48 publications

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“…The association between the APOE polymorphism, thyroid function and cognitive status appears to be unexpectedly close and complex and obviously requires further investigation to dissolve discrepancies observed between studies. In a randomized, cross-sectional, population-based cohort study, Parsaik et al [47 studied ]the association of clinical and subclinical hypothyroidism and mild cognitive impairment. These authors did not find a significant association between thyroid status and mild cognitive impairment in elderly individuals, including ε4 allele carriers.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Bojar¹,

Stasiak²,

Cyniak-Magierska³

et al. 2016

Dement Geriatr Cogn Disord

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Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine.

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Section: Discussionmentioning

confidence: 99%

Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Bojar¹,

Stasiak²,

Cyniak-Magierska³

et al. 2016

Dement Geriatr Cogn Disord

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“…Studies measuring TRH levels in the CSF have reported either increases (Banki et al, 1992) or decreases (Oram et al, 1981) in AD subjects, while a postmortem study found no differences in the hypothalamus and extrahypothalamic areas (Yates et al, 1983). Similarly, studies in which TSH and thyroid hormones were measured reported increases, decreases, or no differences in AD (Ganguli et al, 1996; Johansson et al, 2013; Parsaik et al, 2014; Quinlan et al, 2010; Tan et al, 2008; van Osch et al, 2004). More appropriately, one study evaluated the function of the entire HPT axis by measuring serum TRH, TSH, and thyroid hormones in AD subjects (Yong-Hong et al, 2013) and found levels lower than controls.…”

Section: Alterations In Hypothalamic Function In Admentioning

confidence: 93%

Metabolic and Non-Cognitive Manifestations of Alzheimer’s Disease: The Hypothalamus as Both Culprit and Target of Pathology

2015

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Alzheimer’s disease (AD) is increasingly recognized as a complex neurodegenerative disease beginning decades prior to the cognitive decline. While cognitive deficits remain the cardinal manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in body weight and neuroendocrine functions are also present, often preceding the cognitive decline. Furthermore, hypothalamic dysfunction can also be a driver of AD pathology. Here we offer a brief appraisal of hypothalamic dysfunction in AD, and provide insight into an underappreciated dual role of the hypothalamus as both a culprit and target of AD pathology, as well as into new opportunities for therapeutic interventions and biomarker development.

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“…In addition, the efficacy of antidepressant agents among euthyroid individuals is potentiated when associated with the administration of thyroid hormone, either levothyroxine or liothyronine. 103,104 In some clinical studies, but not all, 105 a residual cognitive dysfunction exists in patients with hypothyroidism who are treated with levothyroxine. 9,53,106,107 Whether these residual symptoms are a consequence of low serum levels of T 3 , or a high T 4 to T 3 ratio, 108,109 remains to be determined.…”

Section: Mood Disorders and Cognitionmentioning

confidence: 99%

Scope and limitations of iodothyronine deiodinases in hypothyroidism

et al. 2015

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The coordinated expression and activity of the iodothyronine deiodinases regulate thyroid hormone levels in hypothyroidism. Once heralded as the pathway underpinning adequate thyroid-hormone replacement therapy with levothyroxine, the role of these enzymes has come into question as they have been implicated in both an inability to normalize serum levels of tri-iodothyronine (T3) and the incomplete resolution of hypothyroid symptoms. These observations, some of which were validated in animal models of levothyroxine monotherapy, challenge the paradigm that tissue levels of T3 and thyroid-hormone signalling can be fully restored by administration of levothyroxine alone. The low serum levels of T3 observed among patients receiving levothyroxine monotherapy occur as a consequence of type 2 iodothyronine deiodinase (DIO2) in the hypothalamus being fairly insensitive to ubiquitination. In addition, residual symptoms of hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that might be a risk factor for neurodegenerative disease. Here, we discuss how these novel findings underscore the clinical importance of iodothyronine deiodinases in hypothyroidism and how an improved understanding of these enzymes might translate to therapeutic advances in the care of millions of patients with this condition.

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Hypothyroidism and Risk of Mild Cognitive Impairment in Elderly Persons

Cited by 59 publications

References 48 publications

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Metabolic and Non-Cognitive Manifestations of Alzheimer’s Disease: The Hypothalamus as Both Culprit and Target of Pathology

Scope and limitations of iodothyronine deiodinases in hypothyroidism

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