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      Parathyroid Hormone, Cognitive Function and Dementia: A Systematic Review

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          Abstract

          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.

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          Most cited references42

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          Vitamin D, cognition, and dementia: a systematic review and meta-analysis.

          Cynthia M. Balion, Lauren Griffith, Lisa Strifler … (2012)
          To examine the association between cognitive function and dementia with vitamin D concentration in adults. Five databases were searched for English-language studies up to August 2010, and included all study designs with a comparative group. Cognitive function or impairment was defined by tests of global or domain-specific cognitive performance and dementia was diagnosed according to recognized criteria. A vitamin D measurement was required. Two authors independently extracted data and assessed study quality using predefined criteria. The Q statistic and I² methods were used to test for heterogeneity. We conducted meta-analyses using random effects models for the weighted mean difference (WMD) and Hedge's g. Thirty-seven studies were included; 8 contained data allowing mean Mini-Mental State Examination (MMSE) scores to be compared between participants with vitamin D <50 nmol/L to those with values ≥50 nmol/L. There was significant heterogeneity among the studies that compared the WMD for MMSE but an overall positive effect for the higher vitamin D group (1.2, 95% confidence interval [CI] 0.5 to 1.9; I² = 0.65; p = 0.002). The small positive effect persisted despite several sensitivity analyses. Six studies presented data comparing Alzheimer disease (AD) to controls but 2 utilized a method withdrawn from commercial use. For the remaining 4 studies the AD group had a lower vitamin D concentration compared to the control group (WMD = -6.2 nmol/L, 95% CI -10.6 to -1.8) with no heterogeneity (I² < 0.01; p = 0.53). These results suggest that lower vitamin D concentrations are associated with poorer cognitive function and a higher risk of AD. Further studies are required to determine the significance and potential public health benefit of this association.
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            Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop.

            John Bilezikian, Aliya Khan, John Potts (2009)
            Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostics and management for this condition in clinical practice. Interested professional societies selected representatives for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed and at subsequent discussions. Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. Consensus was achieved by a group meeting. Statements were prepared and reviewed by all authors who represented the Planning Committee and the participating professional societies.
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              Vitamin D and neurocognitive dysfunction: preventing "D"ecline?

              Jennifer Buell, Bess Dawson-Hughes (2008)
              A preponderance of evidence supports a role for vitamin D beyond the classical function in mineral homeostasis. Epidemiologic investigations have revealed a beneficial role of vitamin D in muscle function, cardiovascular health, diabetes, and cancer prevention. More recently, studies have suggested a potential beneficial role of vitamin D in cognitive function. Vitamin D exhibits functional attributes that may prove neuroprotective through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction and detoxification mechanisms. Compelling evidence supports a beneficial role for the active form of vitamin D in the developing brain as well as in adult brain function. The vitamin D receptor and biosynthetic and degradative pathways for the hydroxylation of vitamin D have been found in the rodent brain; more recently these findings have been confirmed in humans. The vitamin D receptor and catalytic enzymes are colocalized in the areas of the brain involved in complex planning, processing, and the formation of new memories. These findings potentially implicate vitamin D in neurocognitive function.
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                Author and article information

                Contributors
                Terence J Quinn: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 26 May 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 5
                Electronic Location Identifier: e0127574
                Affiliations
                [1 ]The National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC), University of Exeter Medical School, University of Exeter, Exeter, United Kingdom
                [2 ]University of Exeter Medical School, University of Exeter, Exeter, United Kingdom
                University of Glasgow, UNITED KINGDOM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Wrote the paper: IL DJL. Conceived the review: DJL. Designed the review: IL JTC DJL. Titles, abstracts and full texts screening, application of inclusion and exclusion criteria: IL MS. Data extraction and quality appraisal: IL. Data extraction and quality appraisal checked by: MS EK. Data interpretation: IL MS CMD EK KK DJL. Critically revised the manuscript for important intellectual content and approved the final version: IL JTC CMD MS EK KK DJL.

                Article
                Publisher ID: PONE-D-15-05460
                DOI: 10.1371/journal.pone.0127574
                PMC ID: 4444118
                PubMed ID: 26010883
                SO-VID: 844fa160-312e-41ed-a1bd-670740e92e98
                Copyright statement: Copyright @ 2015
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 5 February 2015
                Date accepted : 16 April 2015
                Page count
                Figures: 1, Tables: 3, Pages: 16
                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.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
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