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Original research
Distinct disease mechanisms may underlie cognitive decline related to hearing loss in different age groups
  1. Jochum J van 't Hooft1,2,
  2. Wiesje Pelkmans1,2,
  3. Jori Tomassen1,2,
  4. Cas Smits3,
  5. Nienke Legdeur1,2,
  6. Anouk den Braber1,2,
  7. Frederik Barkhof4,5,
  8. Bart van Berckel4,
  9. Maqsood Yaqub4,
  10. Philip Scheltens1,2,
  11. Yolande AL Pijnenburg1,2,
  12. Pieter Jelle Visser1,2,6,
  13. Betty M Tijms1,2
  1. 1 Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands
  2. 2 Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
  3. 3 Otolaryngology ‐ Head and Neck Surgery, Ear and Hearing, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  4. 4 Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
  5. 5 UCL Institutes of Neurology and Healthcare Engineering, University College London, London, UK
  6. 6 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands
  1. Correspondence to Mr Jochum J van 't Hooft, Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands; j.vanthooft{at}


Background Hearing loss in older adults is associated with increased dementia risk. Underlying mechanisms that connect hearing loss with dementia remain largely unclear.

Methods We studied the association of hearing loss and biomarkers for dementia risk in two age groups with normal cognition: 65 participants from the European Medical Information Framework (EMIF)-Alzheimer’s disease (AD) 90+ study (oldest-old; mean age 92.7 years, 56.9% female) and 60 participants from the EMIF-AD PreclinAD study (younger-old; mean age 74.4, 43.3% female). Hearing function was tested by the ‘digits-in-noise test’ and cognition by repeated neuropsychological evaluation. Regressions and generalised estimating equations were used to test the association of hearing function and PET-derived amyloid burden, and linear mixed models were used to test the association of hearing function and cognitive decline. In the oldest-old group, mediation analyses were performed to study whether cognitive decline is mediated through regional brain atrophy.

Results In oldest-old individuals, hearing function was not associated with amyloid pathology (p=0.7), whereas in the younger-old individuals hearing loss was associated with higher amyloid burden (p=0.0034). In oldest-old individuals, poorer hearing was associated with a steeper decline in memory, global cognition and language, and in the younger-old with steeper decline in language only. The hippocampus and nucleus accumbens mediated the effects of hearing loss on memory and global cognition in the oldest-old individuals.

Conclusions Hearing loss was associated with amyloid binding in younger-old individuals only, and with cognitive decline in both age groups. These results suggest that mechanisms linking hearing loss with risk for dementia depends on age.


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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  • Contributors Study concept and design: JJvH, BMT, YLPP and PJV. Writing the first drafts of the manuscript: JJvH. Analysis and interpretation of data: JJvH, WP, JT and BMT. Critical revision of the manuscript for important intellectual content: JJvH, WP, JT, CS, NL, AdB, FB, BvB, MY, PS, YLPP, PJV and BMT. Recruiting patients and collecting data: JT, NL and AdB. Scientific advisor, analysis and collection of structural imaging data: WP and FB. Scientific advisor, analysis and collection of amyloid-PET data: BvB, MY. Scientific advisor on the digits-in-noise test: CS. Supervision: BMT, YLPP. Obtained funding: PJV. BMT is responsible for the overall content as the guarantor.

  • Funding This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant No. 115372), the Dutch Alzheimer’s association and the Dutch Alzheimer rally.

  • 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.