Hayden, Kathleen M.

AbstractBackgroundPrior longitudinal studies among older adults have documented associations between hearing loss and changes in brain morphology. Whether interventions involving hearing aids can reduce age‐related atrophy is unknown. A substudy within the Aging and Cognitive Health Evaluation in Elders (ACHIEVE, Clinicaltrials.gov Identifier: NCT03243422) randomized controlled trial tested the effect of a best‐practices hearing intervention versus health education control on three‐year change in cortical thickness among older adults with hearing loss.MethodThe ACHIEVE study enrolled 977 community‐dwelling adults aged 70‐84 years at baseline (2018‐2019) with untreated hearing loss (better ear pure tone average [0.5‐4 kHz] ≥30 and <70 dB HL) and without substantial cognitive impairment from four sites across the U.S. (Jackson, MS, Forsyth County, NC, Minneapolis, MN, Washington County, MD). Participants were randomized to a hearing intervention (provision of hearing aids and related technologies, counseling, and education) or a health education control (individual sessions with a health educator covering topics relevant to chronic disease and disability prevention). Three‐dimensional magnetic resonance imaging was performed on 3 Tesla Siemens scanners in a subsample of 445 participants at the ACHIEVE baseline and three‐year follow‐up. Linear mixed effects models were used in intention‐to‐treat analyses to estimate three‐year change in cortical thickness. All models adjusted for baseline measures of hearing loss, recruitment source, site, age, sex, and education. Missing outcome and covariate data was imputed to mitigate bias caused by informative attrition.ResultAt baseline, 224 participants were women (50.3%), 52 participants were Black (11.7%), and the mean (SD) age was 76.4 (4.0) years old (Table 1). Compared to the health education control, the hearing intervention exhibited a nominally protective effect on three‐year change in average cortical thickness (Figure 1). The greatest effect size for cortical thickness was observed in the occipital lobe, while the smallest effect size was detected in the temporal lobe. Statistically significant effects were detected in the pars orbitalis, rostral anterior cingulate, posterior cingulate, and isthmus cingulate (Figure 2).ConclusionHearing aid use may reduce decline in cortical thickness among older adults. The effects of hearing aids may be greatest in regions other than those associated with the auditory cortex.

Purpose: Population-based evidence in the interrelationships among hearing, brain structure, and cognition is limited. This study aims to investigate the cross-sectional associations of peripheral hearing, brain imaging measures, and cognitive function with speech-in-noise performance among older adults. Method: We studied 602 participants in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) brain magnetic resonance imaging (MRI) ancillary study, including 427 ACHIEVE baseline (2018–2020) participants with hearing loss and 175 Atherosclerosis Risk in Communities Neurocognitive Study Visit 6/7 (2016–2017/2018–2019) participants with normal hearing. Speech-in-noise performance, as outcome of interest, was assessed by the Quick Speech-in-Noise (QuickSIN) test (range: 0–30; higher = better). Predictors of interest included (a) peripheral hearing assessed by pure-tone audiometry; (b) brain imaging measures: structural MRI measures, white matter hyperintensities, and diffusion tensor imaging measures; and (c) cognitive performance assessed by a battery of 10 cognitive tests. All predictors were standardized to z scores. We estimated the differences in QuickSIN associated with every standard deviation ( SD ) worse in each predictor (peripheral hearing, brain imaging, and cognition) using multivariable-adjusted linear regression, adjusting for demographic variables, lifestyle, and disease factors (Model 1), and, additionally, for other predictors to assess independent associations (Model 2). Results: Participants were aged 70–84 years, 56% female, and 17% Black. Every SD worse in better-ear 4-frequency pure-tone average was associated with worse QuickSIN (−4.89, 95% confidence interval, CI [−5.57, −4.21]) when participants had peripheral hearing loss, independent of other predictors. Smaller temporal lobe volume was associated with worse QuickSIN, but the association was not independent of other predictors (−0.30, 95% CI [−0.86, 0.26]). Every SD worse in global cognitive performance was independently associated with worse QuickSIN (−0.90, 95% CI [−1.30, −0.50]). Conclusions: Peripheral hearing and cognitive performance are independently associated with speech-in-noise performance among dementia-free older adults. The ongoing ACHIEVE trial will elucidate the effect of a hearing intervention that includes amplification and auditory rehabilitation on speech-in-noise understanding in older adults. Supplemental Material: https://doi.org/10.23641/asha.25733679

AbstractBackgroundHearing loss is associated with greater cognitive decline and incident dementia. Whether hearing intervention could reduce cognitive decline in older adults with hearing loss is unknown.MethodThe ACHIEVE study is a randomized trial (NCT03243422) of 70‐84 year‐old adults with untreated hearing loss and free from substantial cognitive impairment that took place at four U.S. sites. Participants were recruited from two study populations: 1) a group of adults participating in a longstanding observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and 2) a group of healthy de novo community volunteers. Participants were randomised (1:1) to hearing intervention (HI; audiological counseling and provision of hearing aids) or a successful aging health education control intervention (SA; sessions with a health educator on chronic disease prevention). The primary intention‐to‐treat endpoint was 3‐year change in a global cognition standardized factor score from a comprehensive neurocognitive battery.Result977 participants (238 ARIC, 739 de novo) underwent randomisation; 490 were assigned to HI and 487 to SA control. Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than the de novo group. In the primary analysis combining the ARIC and de novo groups, 3‐year cognitive change (in S.D. units) was not significantly different between HI and SA control (HI: ‐0·200 [95% CI: ‐0·256,‐0·144]; SA: ‐0·202 [‐0·258,‐0·145]; Difference 0·002 [‐0·077,0·081],p = 0·96). However, prespecified analyses demonstrated significant differences in the effect of HI on cognitive change between the ARIC and de novo group (p interaction = 0·010). In the ARIC group, HI was associated with a 48% reduction in 3‐year cognitive change compared to SA control (HI: ‐0·211 [‐0·349,‐0·073]; SA: ‐0·402 [‐0·536, ‐0·267]; Difference 0·191 [0·022,0·360,p = 0·027]). In the de novo group, cognitive change was not significantly different between HI and SA control (HI: ‐0·213 [‐0·277,‐0·148]; SA: ‐0·151 [‐0·215,‐0·087]; Difference ‐0·061 [‐0·151,0·028,p = 0·18]). The rate of cognitive change among control participants was observed to be 2.7‐fold faster in the ARIC versus de novo group.ConclusionHearing intervention may have a significant effect on reducing cognitive change over 3 years in populations of older adults at increased risk for cognitive decline.

AbstractBackgroundHearing loss is associated with cognitive decline and dementia. The ongoing ACHIEVE Study was the first randomized trial to test the effects of hearing treatment on three‐year cognitive change. The ACHIEVE – Brain Health Follow‐Up Study will extend follow‐up to six years post‐randomization to determine the long‐term and potentially nonlinear effects of hearing treatment vs. health education control with delayed treatment on dementia and cognitive decline.MethodsParticipants will be recruited from the 977 participants enrolled in the ACHIEVE Study. After Year 3, hearing intervention participants will continue to receive hearing care and the control group will be offered the hearing intervention. Co‐primary study outcomes will be cognitive decline and a composite of incident mild cognitive impairment (MCI)/probable dementia. Secondary outcomes include domain‐specific cognitive decline, brain structural changes on magnetic resonance imaging (MRI), and other functional outcomes (e.g., physical activity, social isolation). Power analyses for the co‐primary outcomes assumed an annual attrition rate of 10% and an immediate, lagged, or cumulative treatment effect.ResultsWhen comparing multi‐year cognitive decline (Table 1), in the scenario of a constant treatment effect that assumes a strong and immediate treatment effect, the benefit of extended follow‐up is not greater power, but additional information on the long‐term effects of hearing intervention. In a scenario of a lagged treatment effect, a two‐year lag in the treatment effect causes the Year 3 assessment to be severely underpowered (28%) but provides sufficient power (80%) at Year 6 despite attrition. In a scenario of a cumulative treatment effect that increases with time, analyses are similarly underpowered at Year 3 (65%) but not at Year 6 (82%). The same pattern is evident when estimating the power at Year 3 (57%) and Year 6 (80%) to detect incident MCI/probable dementia in a Cox regression model that assumes a protective hazard ratio of 0.70 (Figure 1).ConclusionAcross all non‐constant scenarios of potential treatment effect, six years of follow‐up increases precision and provides valuable information to better delineate long‐term cognitive trajectories. The ACHIEVE ‐ Brain Health Follow‐Up Study will be completed in 2025.

AbstractBackgroundThe effect of an intensive lifestyle intervention (ILI) on Alzheimer’s disease (AD) blood‐based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study.MethodParticipants aged 45‐76 years were randomized at baseline to a 10‐year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8‐18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end‐of‐intervention plasma samples were analyzed with the Quanterix Simoa HD‐X Analyzer. Changes in Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z‐scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE‐ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing.ResultThe mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration >5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (‐0.04 ±0.01; p = 0.002), global cognition scores (‐0.05 ±0.02; p = 0.011), executive function (‐0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR] 1.10, 95% CI 1.02‐1.19). Increases in GFAP predicted lower memory (‐0.10 ±0.03; p = 0.0001), global cognition (‐0.09 ±0.03; p = 0.009), executive function scores (‐0.12 ±0.03; p<0.0001), and increased risk of MCI/probable dementia (OR 1.24, 95% CI 1.09‐1.41).ConclusionThere was no association between the intervention and changes in biomarker levels. Increasing levels of NfL and GFAP over the ∼10 year period were associated with reduced cognitive performance and increased risk of MCI/probable dementia.

Abstract Speech-in-noise performance is fundamental to daily communications and comprehensive characterization is needed. We studied 590 dementia-free participants aged 70-84 years, including 428 hearing-impaired participants from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study baseline (2018-19), which is a randomized controlled trial partially nested within the Atherosclerosis Risk in Communities (ARIC) Study, and 162 normal-hearing ARIC Visit 6/7 (2016-17/2018-19) participants. The Quick Speech-in-Noise (QuickSIN) test was used to measure speech-in-noise performance. Predictors included (1) Four-frequency better-ear pure-tone average (PTA); (2) Magnetic resonance imaging (MRI) measures (total and lobar volumes, diffusion tensor imaging, white matter hyperintensities); (3) Global and domain-specific (language, memory, executive function) cognitive performance. All predictors were standardized to Z-scores. We used multivariable-adjusted linear regression, adjusting for demographic and disease covariates. PTA and cognitive performance, but not MRI measures, were independently associated with speech-in-noise performance, with PTA explaining the largest variance, indicating the promising role of hearing aids.

AbstractBackgroundPrior evidence has suggested associations between hearing loss and smaller brain volumes particularly in the temporal lobe where the primary auditory cortex is located, probably due to changes in cortical organization associated with reduced auditory stimulation. Evidence regarding associations of central auditory processing with brain volumes is relatively limited. The study aims to investigate cross‐sectional associations of central auditory processing with brain volumes in older adults.MethodWe studied 587 cognitively normal (Mini‐Mental State Exam ≥23 if high school degree or less and ≥25 if above high school degree) older adults (mean age: 77±4 years, 56% female, 17% black), including 426 with hearing loss from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) baseline (2018‐19), which is an ancillary randomized controlled trial of the Atherosclerosis Risk in Communities (ARIC) Study and 161 with normal hearing, comparable age and cognitive status from the ARIC Visit 6/7 (2016‐17/2018‐19). Brain volumes were measured by magnetic resonance imaging (MRI) scans and were transformed to z‐scores. Central auditory processing was measured by the Quick Speech‐in‐Noise (QuickSIN) test. Total scores range from 0 to 30 with lower scores indicating worse speech‐in‐noise performance. Multivariable‐adjusted linear regression was used to estimate cross‐sectional differences in standardized brain volumes associated with differences in QuickSIN score. Models adjusted for age, sex, race, education, cohort, body mass index, smoking, hypertension, diabetes, stroke, intracranial volume, and pure‐tone average.ResultEvery 5‐point decrease in QuickSIN score (worse performance) was associated with smaller volumes of the temporal lobe (‐0.07SD, 95% CI: ‐0.13, ‐0.01). QuickSIN score was also associated with subregions of the temporal lobe related to auditory processing, memory and emotion, including amygdala (‐0.13SD, 95% CI: ‐0.21, ‐0.04), middle (‐0.08SD, 95% CI: ‐0.15, ‐0.00) and superior temporal gyri (‐0.08SD, 95% CI: ‐0.15, ‐0.01).ConclusionPoorer central auditory processing was associated with smaller temporal lobe volumes, including but not limited to subregions important for auditory processing. The ongoing collection of ACHIEVE data with longitudinal MRI data will facilitate understanding of association between hearing loss and brain atrophy as well as the potential promising effects of hearing treatment in mitigating brain aging.

Abstract We investigated the cross-sectional associations of speech-in-noise performance with magnetic resonance imaging brain volumes among 588 cognitively normal participants (77±4 years, 56% female) from the Aging and Cognitive Health Evaluation in Elders Study (randomized trial embedded in the Atherosclerosis Risk in Communities (ARIC) Study) baseline in 2018-19 (N=427, with hearing loss) and ARIC (N=161, normal hearing) Visit 6/7 in 2016-17/2018-19. Central auditory processing was measured by Quick Speech-in-Noise (QuickSIN) test; range: 0 to 30, lower scores=worse performance. In models adjusted for demographic and disease covariates, every 5-point decrease in QuickSIN score was associated with smaller volumes of the temporal lobe overall (-0.07SD, 95% CI:-0.13,-0.01) as well as subregions including but not limited to those important for auditory processing (amygdala:-0.13SD, 95% CI:-0.21,-0.04; middle temporal gyrus:-0.08SD, 95% CI:-0.15,-0.00; superior temporal gyrus:-0.08SD, 95% CI:-0.15,-0.01). Further research is needed to understand the mechanisms underlying these observed associations.

Abstract White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.