Parathyroid Hormone, Cognitive Function and Dementia: A Systematic Review

Abstract

BackgroundMetabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer’s disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not.MethodsWe conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies.ResultsThe twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains.ConclusionsMixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.

Review of Hypoparathyroidism

“…Higher incidence of anxiety, depression, and overall reduced quality of life occurs in patients with hypoparathyroidism compared to normal control groups (8, 25, 26). However, one systematic review failed to show a link between PTH and cognitive dysfunction and dementia (27), so it is assumed that these conditions are mostly due to the calcium disturbance.…”

Bone-brain crosstalk and potential associated diseases

“…As a result, Ocn promotes glucose homeostasis, enhances energy expenditure and prevents the appearance of glucose intolerance induced by high fat diet (Figure 2). Moreover, Ocn favors male reproductive functions in mice by promoting testosterone biosynthesis by the testis, following its binding to a receptor expressed in Leydig cells, Gprc6a, that belongs to the G-protein coupled receptor family [24,[29][30][31]81] (Figure 2). It was also shown that Gprc6a is expressed in pancreatic β-cells and that it is also the receptor mediating Ocn influences on the energy metabolism [32].…”

“…This makes it unlikely that this receptor transduces Ocn signals in the brain. This last notion is also important because it implies that the passivity of the Ocn-/-mice is not a mere consequence of metabolic or reproductive abnormalities, since these are equally severe in Ocn-/-and Gprc6a-/-mice [24,30,86,87]. Mother-derived osteocalcin crosses the placental barrier from E14.5 until birth and influences brain development by preventing neuronal apoptosis.…”

“…This is particularly true for the bone for which multiple genetic-based studies have shed light on the growing physiological importance of this organ in whole-body homeostasis [17][18][19]. Beyond the classical view of the skeleton describing it as a relatively static tissue, the bone secretes at least two molecules influencing whole-body homeostasis [18,[20][21][22][23][24]. First, fibroblast growth factor 23 (FGF23), a protein synthesized by osteoblasts and osteocytes and released into general circulation, regulates phosphocalcic metabolism in multiple tissues [21,25,26].…”

Hypoparathyroidism: disease update and new methods of treatment

“…Действительно, результа-ты исследований подтвердили более высо-кий уровень тревожности, депрессии и сни-жение качества жизни в данной когорте больных [1,28,29]. Однако в другом систе-матическом обзоре не выявлено корреляции уровня ПТГ с когнитивной дисфункцией и деменцией [30], поэтому вероятнее всего данные нарушения психической функции связаны с гипокальциемией. Кроме того, при гипопаратиреозе повышен риск развития ка-таракты [29], нарушения состояния эмали зубов [31] и кальцификации базальных ган-глиев [1].…”