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Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age
  1. Anat Rotstein1,
  2. Arad Kodesh2,3,
  3. Yair Goldberg4,
  4. Abraham Reichenberg1,5,
  5. Stephen Z Levine2
  1. 1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  2. 2Department of Community Mental Health, University of Haifa, Haifa, Israel
  3. 3Department of Mental Health, Meuhedet Health Services, Tel Aviv, Israel
  4. 4The Faculty of Industrial Engineering and Management, Technion–Israel Institute of Technology, Haifa, Israel
  5. 5Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  1. Correspondence to Dr Anat Rotstein, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; anat.rotstein{at}mssm.edu

Abstract

Background The association between serum folate deficiency and the risk of dementia in old age is unclear, perhaps owing to small sample sizes, the competing risk of mortality or reverse causation.

Objective To examine the associations between serum folate deficiency and the risks of incident dementia and all-cause mortality in a large national sample of older adults.

Methods A prospective cohort aged 60–75 years (n=27 188) without pre-existing dementia for at least 10 years, was tested for serum concentrations of folate and followed up for dementia or all-cause mortality. Serum folate deficiency was classified as present (<4.4 ng/mL), otherwise absent. HRs and 95% CIs from competing risks Cox models were fitted to quantify the associations between serum folate deficiency and the risks of dementia and all-cause mortality. To examine reverse causation, the analysis was stratified by duration of follow-up.

Findings The presence compared with the absence of serum folate deficiency was associated with higher risks of dementia (HR=1.68; 95% CI 1.32 to 2.13; p<0.001) and all-cause mortality (HR=2.98; 95% CI 2.52 to 3.52; p<0.001). Evidence for reverse causation were moderate for dementia and mild for all-cause mortality.

Conclusions Serum concentrations of folate may function as a biomarker used to identify those at risk of dementia and mortality; however, reverse causation is likely. Further research is needed to examine the role of serum folate deficiency in dementia aetiology.

Clinical implications Serum folate deficiency in older adults requires monitoring and treatment for preventative measures and/or as part of implemented therapeutic strategies.

  • delirium & cognitive disorders
  • adult psychiatry

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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Footnotes

  • Twitter @Arotstein, @szlevine

  • Contributors AR, AK, ARE and SZL designed the study; AR, YG and SZL analysed the data; AR drafted the manuscript; and AR and SZL wrote the manuscript. All authors provided critical manuscript feedback.

  • Funding AR is supported by the Zuckerman-CHE Israeli Women Postdoctoral Scholarship.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.