A pilot randomized controlled trial of hearing aids to improve mood and cognition in older adults.
ABSTRACT: OBJECTIVES:Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN:N = 13 individuals aged ?60?years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average???30?dB) were randomized to receive full- (active) vs low-amplification (sham) HAs added to psychiatric treatment as usual. Duration of HA use in hours/day, adverse events frequency, attrition rate, and maintenance of the study blinding were the primary outcome measures. RESULTS:Compliance with HAs was excellent (>9 hours/day for both groups) and rates of adverse events and drop-outs did not differ between groups. Preliminary data demonstrated differential improvement for active vs sham HAs on hearing functioning (Hearing Handicap Inventory for the Elderly [nonparametric effect size (np-ES) = 0.62]), depressive symptoms (Inventory for Depressive Symptomatology [np-ES = 0.31]), cognition (Repeatable Battery for the Assessment of Neuropsychological Status Immediate Memory [np-ES = 0.25]), and general functioning (World Health Organization Disability Assessment Schedule [np-ES = 0.53]). Significantly greater than 50% of both groups correctly guessed their treatment assignment, indicating incomplete concealment of treatment allocation. CONCLUSIONS:This pilot RCT for ARHL and late-life depression was feasible to execute and showed clinical promise, but improved methods of blinding the experimental treatments are needed. Larger studies should investigate whether hearing remediation may be an effective preventative and/or therapeutic strategy for late-life depression and cognitive decline.
Project description:Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive hearing impairment leads to social isolation and is also associated with comorbidities, such as frailty, falls, and late-onset depression. Moreover, there is a growing evidence linking it with cognitive decline and increased risk of dementia. Given the large social and welfare burden that results from ARHL, and because ARHL is potentially a modifiable risk factor for dementia, there is an urgent need for therapeutic interventions to ameliorate age-related auditory decline. However, a prerequisite for design of therapies is knowledge of the underlying molecular mechanisms. Currently, our understanding of ARHL is very limited. Here, we review recent findings from research into ARHL from both human and animal studies and discuss future prospects for advances in our understanding of genetic susceptibility, pathology, and potential therapeutic approaches in ARHL.
Project description:Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL.
Project description:Validation for depression in preschool children has been established; however, to date no empirical investigations of interventions for the early onset disorder have been conducted. Based on this and the modest efficacy of available treatments for childhood depression, the need for novel early interventions has been emphasized. Large effect sizes (ES) for preschool psychotherapies for several Axis I disorders suggest that earlier intervention in depression may also be promising. Therefore, a novel form of treatment for preschool depression, Parent-Child Interaction Therapy Emotion Development (PCIT-ED) was developed and tested.A preliminary randomized controlled trial (RCT) was conducted comparing PCIT-ED to psycho-education in depressed 3- to 7-year-olds and their caregivers. A total of 54 patients met symptom criteria for DSM-IV major depressive disorder and were randomized, 19 patients completed the active treatment (n = 8 dropouts) and 10 completed psycho-education (n = 17 dropouts).Both groups showed significant improvement in several domains, with PCIT-ED showing significance in a greater number of domains. An intent-to-treat analysis suggested that PCIT-ED was significantly more effective than psycho-education on executive functioning (p = .011, ES = 0.12) and emotion recognition skills (p = .002, ES = 0.83).The RCT proved feasible and suggests an individual control condition should be used in future trials to minimize differential dropout. These pilot data, although limited by power, suggest that PCIT-ED may be a promising early intervention for depression. Larger scale randomized controlled trials of PCIT-ED for depressed preschoolers are now warranted.
Project description:Background and Objectives:Research has shown that dual sensory loss is a risk factor for depression in older adults. However, validated measures of depression for people with dual sensory loss are lacking. The purpose of the present study was to investigate the construct validity and reliability of the Major Depression Inventory for use among elderly persons with acquired dual sensory loss. Research Design and Methods:A cross-sectional questionnaire survey was conducted in a national sample of people ?50 years of age with functional acquired dual sensory loss. Of the invited participants, 302 (66%) returned the questionnaire and 207 complete cases were included for analysis. Rasch models and graphical log-linear Rasch models were used for item analysis. Lack of differential item functioning was tested relative to severity of vision and hearing impairment, mode of questionnaire completion, age, sex, comorbidity, instrumental activities of daily living, social position, and cohabitation status. Results:The 10-item Major Depression Inventory did not fit the Rasch model. An 8-item version, excluding the items "feeling sad" and "sleep problems," fit a graphical log-linear Rasch model. No evidence of differential item functioning was discovered, thus the 8-item Major Depression Inventory was measurement invariant across severity of impairments and mode of completing the questionnaire. The overall reliability was 0.81 and ranged from acceptable to good for all subgroups of participants, except males with severe hearing impairment and low functional status. Consequently, the 8-item version of the Major Depression Inventory was considered construct valid and reliable within the frame of reference. Discussion and Implications:An 8-item version of the Major Depression Inventory can be used to screen for depressive symptoms in elderly persons with acquired dual sensory loss.
Project description:Age-related hearing loss (ARHL) is the most common sensory disorder among the elderly, associated with aging and auditory hair cell death due to oxidative-stress-induced mitochondrial dysfunction. Although transgenic mice and long-term aging induction cultures have been used to study ARHL, there are currently no ARHL animal models that can be stimulated by intermittent environmental changes. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined on the basis of expression of hearing-loss-induced phenotypes and aging-related factors. The incidence of hearing loss was significantly higher in dual- and triple-exposure conditions than in intermittent hypoxic conditions, high-fat diet (HFD), or d-galactose injection alone. Continuous oxidative stress and HFD accelerated cellular aging. An increase in Ucp2, usually expressed during mitochondrial dysfunction, was observed. Expression of Cdh23, Slc26a4, Kcnq4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in the cells of the hearing organ. We found that intermittent hypoxia, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects the effects of intermittent environmental changes, will benefit future research on ARHL.
Project description:Age-related hearing loss (ARHL) has been considered as a promising modifiable risk factor for cognitive impairment and dementia. Nonetheless, it is still unclear whether age-related hearing loss associates with neurodegenerative biomarkers of Alzheimer's disease (AD). Participants with ARHL were selected from the established Alzheimer's Disease Neuroimaging Initiative (ADNI) database. In multivariable models, the cross-sectional and longitudinal associations of ARHL with CSF ?-amyloid (A?) and tau measurements, brain A? load, and cortical structural measures were explored. ARHL was associated with higher CSF levels of tau (p < 0.001) or ptau181 (p < 0.05) at baseline as well as faster elevation rates of these two types of biomarkers (p < 0.05). Although the baseline volume/thickness of hippocampus (p < 0.05) and entorhinal cortex (p < 0.0005) were higher in individuals with ARHL, these two regions (p < 0.01 for hippocampus, p < 0.05 for entorhinal cortex) displayed significantly accelerated atrophy in individuals with ARHL. No association of ARHL with CSF or brain A? levels was found. Subgroup analyses indicated that the above effects of ARHL were more significant in non-demented stage. Age-related hearing loss was associated with elevated cerebrospinal fluid tau levels and atrophy of entorhinal cortex.
Project description:Growing evidence suggests alterations in cognitive control processes in individuals with varying degrees of age-related hearing loss (ARHL); however, alterations in those with unaided mild ARHL are understudied. The current study examined two cognitive control processes, cognitive flexibility, and inhibition, in 21 older adults with unaided mild ARHL and 18 age- and education-matched normal hearing (NH) controls. All participants underwent comprehensive audiological and cognitive evaluations including Trail Making Test-B, Verbal Fluency, Stroop, and two Go/NoGo tasks. Group differences in cognitive flexibility and inhibition as well as associations between peripheral and central hearing ability and measures of cognitive flexibility and inhibition were investigated. Findings revealed that the ARHL group took significantly longer to complete the Stroop task and had higher error rates on NoGo trials on both Go/NoGo tasks relative to the NH controls. Additionally, poorer peripheral and central hearing were associated with poorer cognitive flexibility and inhibitory control. Our findings suggest slower and more inefficient inhibitory control in the mild ARHL group relative to the NH group and add to decades of research on the association between hearing and cognition.
Project description:Hearing aids are the primary tool in non-medical rehabilitation for individuals with hearing loss. While the costs of the electronic components have reduced substantially, the cost of a hearing aid has risen steadily to the point that it has become unaffordable for the majority of the population with Age-Related Hearing Loss (ARHL) especially for those residing in low- and middle-income countries. Here, we present an ultra-low-cost, affordable and accessible hearing aid device ('LoCHAid'), specifically targeted towards treating ARHL in elderly patients. The LoCHAid components cost 98 cents (< $1) when purchased in bulk for 10,000 units and can be personalized for each user through a 3D-printable case. It is designed to be an over-the-counter (OTC) self-serviceable solution for elderly individuals with ARHL. Electroacoustic measurements show that the device meets most of the targets set out by the WHO Preferred Product Profile and Consumer Technology Association for hearing aids. The frequency response of the hearing aid shows selectable gain in the range of 4-8 kHz, and mild to moderate gain between 200-1000 Hz, and shows very limited total distortion (1%). Simulated gain measurements show that the LoCHAid is well fitted to a range of ARHL profiles for males and females between the ages of 60-79 years. Overall, the measurements show that the device offers the potential to benefit individuals with ARHL. Thus, our proposed design has the potential to address the challenge of affordable and accessible hearing technology for hearing impaired elderly individuals especially in low- and middle-income countries.
Project description:Introduction : Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL). Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL. Methods : Fifty-six listeners (60-72 y/o), 35 participants with ARHL, and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed-training, and no-training group). Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1) Speech-in-noise, (2) time compressed speech, and (3) competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results : Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions : ARHL did not preclude auditory perceptual learning but there was little generalization to untrained conditions. We suggest that most training-related changes occurred at higher level task-specific cognitive processes in both groups. However, these were enhanced by high quality perceptual representations in the normal-hearing group. In contrast, some training-related changes have also occurred at the level of phonemic representations in the ARHL group, consistent with an interaction between bottom-up and top-down processes.
Project description:Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. Although not directly life threatening, it contributes to loss of autonomy and is associated with anxiety, depression and cognitive decline. To search for genetic risk factors underlying ARHL, a large whole-genome sequencing (WGS) approach has been carried out in a cohort of 212 cases and controls, both older than 50 years to select genes characterized by a burden of variants specific to cases or controls. Accordingly, the total variation load per gene was compared and two groups were detected: 375 genes more variable in cases and 371 more variable in controls. In both cases, Gene Ontology analysis showed that the largest enrichment for biological processes (fold?>?5, p-value?=?0.042) was the "sensory perception of sound", suggesting cumulative genetic effects were involved. Replication confirmed 141 genes, while additional analysis based on natural selection led to a prioritization of 21 genes. The majority of them (20 out of 21) showed positive expression in mouse cochlea cDNA and were associated with two functional pathways. Among them, two genes were previously associated with hearing (CSMD1 and PTRPD) and re-sequenced in a large Italian cohort of ARHL patients (N?=?389). Results led to the identification of six coding variants not detected in cases so far, suggesting a possible protective role, which requires investigation. In conclusion, we show that this multistep strategy (WGS, selection, expression, pathway analysis and targeted re-sequencing) can provide major insights into the molecular characterization of complex diseases such as ARHL.