Parathyroid hormone, cognitive function and dementia: a systematic review

PLoS One. 2015 May 26;10(5):e0127574. doi: 10.1371/journal.pone.0127574. eCollection 2015.


Background: Metabolic 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.

Methods: We 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.

Results: The 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.

Conclusions: Mixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / physiopathology
  • Calcium / metabolism*
  • Cognition*
  • Humans
  • Memory*
  • Neurons / metabolism*
  • Parathyroid Hormone / metabolism*


  • Parathyroid Hormone
  • Calcium

Grants and funding

This research has been supported by the National Institute for Health Research (NIHR) South West Peninsula Collaboration for Leadership in Applied Health Research and Care (PenCLAHRC). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. DJL is funded by the Alzheimer’s Association [NIRG-11-200737], the Rosetrees Trust, the Mary Kinross Charitable Trust, the James Tudor Foundation, the Halpin Trust, and the Norman Family Charitable Trust.