Thyroid Function, Alzheimer's Disease and Postoperative Cognitive Dysfunction: A Tale of Dangerous Liaisons?

Abstract

Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. Moreover, thyroid hormones negatively regulate expression of the amyloid-β protein precursor (AβPP), which plays a key role in the development of AD. A condition, the so called euthyroid sick syndrome (ESS), characterized by reduced serum T3 and T4 concentrations without increased serum thyroid stimulation hormone secretion, occurs within hours after major surgery. After surgery, elderly patients often exhibit a transient, reversible state of cognitive alterations. Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.

Postoperative cognitive dysfunction after liver transplantation

“…The serum levels of these two biological markers correlate with the severity of cognitive impairment in Alzheimer's disease (AD) and other cognitive diseases [18,19]. This finding supports the hypothesis that POCD is due to a process similar to that seen in AD [20]. Some patients with POCD appear to exhibit a rapid aging in brain function that is similar to AD [21].…”

Genomics and CSF analyses implicate thyroid hormone in hippocampal sclerosis of aging

“…In the adult mammalian brain, TH plays important roles in metabolic regulation and astrocyte biology [21, 56]. TH dysregulation has been implicated in dementia previously -- both hyperthyroid and hypothyroid states have been linked to dementia [20, 39, 50, 54, 90]. TH has previously been evaluated in CSF [38, 82, 87, 88], with varying results, but was never previously tested in relation to CARTS-type pathology.…”

Serum leptin, thyroxine and thyroid-stimulating hormone levels interact to affect cognitive function among US adults: evidence from a large representative survey

“…Research suggests that thyroxine (T 4 ) and thyroid stimulating hormone (TSH) fluctuations within normal or pre-clinical ranges may be associated with cognitive performance. Evidence suggests hypothyroidism as a potential risk factor for cognitive impairment in some studies (Bono, et al, 2004, Burmeister, et al, 2001, Correia, et al, 2009, Mafrica and Fodale, 2008, Miller, et al, 2006, Monzani, et al, 1993, Osterweil, et al, 1992, Prinz, et al, 1999, Samuels, et al, 2007a, Volpato, et al, 2002, Wahlin, et al, 1998) but not others (Almeida, et al, 2007, Kramer, et al, 2009, Samuels, et al, 2007b). …”