Clinical trial NCT04593290: Listen Carefully: An Exploratory Study of the Association Between Listening Effort and Cognitive Function
Official title: Listen Carefully: An Exploratory Study of the Association Between Listening Effort and Cognitive Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Impairment, Mild
Hearing Loss
Lead sponsor: Technical University of Denmark
Sponsor class: OTHER
Collaborators: name: Danish Dementia Research Centre
First posted: 2020-10-19
Enrollment: 24
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study aims to investigate the association between listening effort and cognitive function for both cognitively healthy individuals and for patients with Mild Cognitive Impairment (MCI) in mid-to-late stages of life, and furthermore to investigate listening effort and cognitive function after several weeks of hearing aid use. Listening effort is measured by the recording of peak pupil dilation during a sentence-final word identification and recall (SWIR) test, cognitive performance is measured using a battery of pen and paper cognitive tests, and hearing loss is measured with pure tone audiometry (PTA). A select number of participants in both the cognitively healthy and MCI group will be administered hearing aids, and the study will re-test both listening effort and cognitive performance.

Detailed description: This is an exploratory proof-of-concept study and an exploratory intervention study with hearing aids in the context of listening effort. With a case (MCI) and control group (cognitively healthy), investigators will examine the associations between listening effort and cognitive function and assess the effect of hearing aid use on both listening effort and cognitive function test scores for those without hearing impairment. There is not sufficient literature to support a sample size calculation for this association study. Investigators will recruit approximately 50 participants. Half of these participants (n=25) will be individuals who have been diagnosed with MCI, according to the Winblad criteria (ICD10), with a Mini Mental State Examination (MMSE) score ≤ 26. The control group of participants (n=25) will be cognitively healthy individuals. All participants will undergo both listening effort testing, coupled with pupillometry and cognitive performance testing, based on a battery of pen-and-paper neuropsychological tests.

As investigators aim to measure cognitive effort exerted when listening and understanding speech in noise, is important that all study participants exhibit a normal sensitivity threshold within the ear canal. This will be assessed using Pure Tone Audiometry (PTA).

Assessment scores for cognitive function will be recorded in a clinical setting, and will be based on a battery of pen-and-paper neuropsychological cognitive tests. The Stroop Test, Trail Making Test (part A \& B), Symbol Digit Modalities Test (SDMT), Verbal Fluency Tests (category: animals and lexical), Rey Complex Figure Test and Logical Memory Test (Part A) will be administered.

The objective measure of listening effort, pupil dilation, will be recorded as a measure of task performance accuracy and pupil dilation will be measured during a SWIR test, which is used to measure speech identification and recall in varying background noise. Prior to the SWIR test, participants undergo an adaptive Danish Hearing in Noise Test (HINT), comprising a list of equally intelligible sentences to be repeated in varying decibel (dB) levels of background noise to determine the individual's speech reception threshold (SRT) at 80% correct responses.

During the SWIR test, the participant is fitted with PupilLabs' eye-tracking system, an open source system consisting of clip-in eye tracking hardware to be placed in a Virtual Reality (VR) headset. To prevent floor and ceiling effects that are independent to baseline pupil size, the illumination within the VR display is individually adapted to the individual's midpoint prior to data collection between dim (\~30 lux) and bright (\~230 lux), with an average illuminance of 110 lux. A software suite allows the capture and post-processing of the data feed, including pupil diameter. For the purpose of this study, the PupilLabs software is controlled via a MATLAB interface.

Everyone who participates in Part 1 (listening effort testing and cognitive testing) will be invited to participate in Part 2 (hearing aids). It is not a requirement to participate in the administration, 6-week use, and re-testing procedures involved in Part 2 of the study. All cognitively healthy participants will be invited to participate, only MCI patients with a live-in informant will be given this opportunity. After ear measurement and dome and wire length selection, Oticon Opn S 1 miniRITE hearing aid fitting will occur wirelessly using Genie software, followed by hearing aid use instructions. The fitting will use Open domes, the second generation of the National Acoustic Laboratories (NAL) fitting protocol (NAL-NL2) and will increase gain seven steps on top of Real Ear Unaided Gain (REUG) from 750 Hz to 6 kHz.

Eligibility criteria: MCI group

Inclusion Criteria:

* Is 40-85 years old;
* Has no other significant neurological or psychiatric disease;
* Has normal hearing (0 - 25 dB thresholds from 250 -6 kHz) measured using PTA;
* Has normal or corrected to normal vision;
* Has an MCI diagnosis, according to Winblad criteria, with a score on the Mini Mental State Examination (MMSE) less than or equal to 26 (MMSE ≤ 26);
* Has a CDR = 0.5;
* Speaks Danish as native language
* (For part 2 of the study - hearing aid use) has a live-in informant.

Exclusion Criteria:

* Takes medication or treatment that could impact the pupillary dilation: eye drops (e.g. atropine or phenylephrine);
* Takes medication or treatment that could impact cognitive function;
* Abuses alcohol or drugs;
* Is unable to comply with study procedures.

Cognitively healthy group:

Inclusion criteria:

* Is 40-85 years old;
* Has a score above 26 on the Mini Mental State Examination (MMSE) (MMSE \> 26);
* Has a CDR Global score = 0;
* Has no significant neurological or psychiatric disease;
* Has Normal hearing (0 - 25 dB thresholds from 250 -6 kHz) measured using PTA;
* Has Normal or corrected to normal vision;
* Speaks Danish as a native language.

Exclusion criteria:

* Meets the criteria for MCI (Winblad criteria) or dementia (ICD 10);
* Takes medication or treatment that could impact the pupillary dilation: eye drops (e.g. atropine or phenylephrine);
* Takes medication or treatment that could impact cognitive function;
* Abuses alcohol or drugs;
* Is unable to comply with study procedures.

Primary outcomes:
measure: Listening effort
timeFrame: Baseline, pre-intervention
measure: The Stroop Color and Word test
timeFrame: Baseline, pre-intervention
measure: Rey Complex Figure Test
timeFrame: Baseline, pre-intervention
measure: Symbol-Digit Modalities Test
timeFrame: Baseline, pre-intervention
measure: Trail Making Test A and B
timeFrame: Baseline, pre-intervention
measure: Verbal Fluency Test (category and lexical)
timeFrame: Baseline, pre-intervention
measure: Logical Memory Test A
timeFrame: Baseline, pre-intervention
Secondary outcomes:
measure: Listening effort post-hearing aid use
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
measure: Logical Memory Test A post-hearing aid use
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
measure: Verbal Fluency Test (category and lexical) post-hearing aid use
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
measure: Trail Making Test A and B - post-hearing aid use
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
measure: Symbol-Digit Modalities Test
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
measure: Rey Complex Figure Test
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
measure: The Stroop Color and Word test
timeFrame: Post-intervention, after 6 weeks of intervention (hearing aid use)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen Memory Clinic, Rigshospitalet
state: Region H
Study officials:
affiliation: DTU - Technical University of Denmark
name: Anja Maier, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pichora-Fuller MK, Kramer SE, Eckert MA, Edwards B, Hornsby BW, Humes LE, Lemke U, Lunner T, Matthen M, Mackersie CL, Naylor G, Phillips NA, Richter M, Rudner M, Sommers MS, Tremblay KL, Wingfield A. Hearing Impairment and Cognitive Energy: The Framework for Understanding Effortful Listening (FUEL). Ear Hear. 2016 Jul-Aug;37 Suppl 1:5S-27S. doi: 10.1097/AUD.0000000000000312.
citation: Zekveld AA, Kramer SE, Festen JM. Cognitive load during speech perception in noise: the influence of age, hearing loss, and cognition on the pupil response. Ear Hear. 2011 Jul-Aug;32(4):498-510. doi: 10.1097/AUD.0b013e31820512bb.
citation: Dawes P, Emsley R, Cruickshanks KJ, Moore DR, Fortnum H, Edmondson-Jones M, McCormack A, Munro KJ. Hearing loss and cognition: the role of hearing AIDS, social isolation and depression. PLoS One. 2015 Mar 11;10(3):e0119616. doi: 10.1371/journal.pone.0119616. eCollection 2015.
citation: Panza F, Solfrizzi V, Logroscino G. Age-related hearing impairment-a risk factor and frailty marker for dementia and AD. Nat Rev Neurol. 2015 Mar;11(3):166-75. doi: 10.1038/nrneurol.2015.12. Epub 2015 Feb 17.
citation: Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimaki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020 Aug 8;396(10248):413-446. doi: 10.1016/S0140-6736(20)30367-6. Epub 2020 Jul 30. No abstract available.
citation: Griffiths TD, Lad M, Kumar S, Holmes E, McMurray B, Maguire EA, Billig AJ, Sedley W. How Can Hearing Loss Cause Dementia? Neuron. 2020 Nov 11;108(3):401-412. doi: 10.1016/j.neuron.2020.08.003. Epub 2020 Aug 31.
citation: Feldman A, Patou F, Baumann M, Stockmarr A, Waldemar G, Maier AM, Vogel A. Listen Carefully protocol: an exploratory case-control study of the association between listening effort and cognitive function. BMJ Open. 2022 Mar 9;12(3):e051109. doi: 10.1136/bmjopen-2021-051109.