Deal, Jennifer A.

Background White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low‐cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI‐only screening design in a hypothetical clinical trial. Methods and Results Data from the Atherosclerosis Risk in Communities study with valid retinal and WMH measurements ( N =1311) were used. To identify a population at greater likelihood of significant WMH on MRI and thus reduce the number of screening MRIs required, we evaluated 3 theoretical prescreening measures: (1) retinal, (2) clinical, (3) combined clinical‐retinal. Given a target sample for clinical trials ( N =646), we calculated screening sample sizes based on the proportion within the population having an elevated score for each prescreening measure (separately) multiplied by the proportion of significant WMH among those with that prescreening feature. Recruitment costs were calculated using estimated retinal and MRI cost estimates. Compared with the estimated cost of MRI‐only screening (>$4.24 million, requiring MRI on 6526 participants), prescreening for a high clinical score resulted in total cost of $2.47 million, with an initial screening group of 52 778 participants, with MRI in 3801. A high clinical‐retinal score cutoff resulted in costs of $2.9 million while requiring 13 572 participants, with 3801 completing MRI. Conclusions A 2‐stage design with low‐cost prescreening measures is a promising approach, resulting in reduced theoretical recruitment costs compared with an MRI‐only design.

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

Background: White matter hyperintensities (WMH) are associated with risk of dementia and stroke, so are an important therapeutic target for clinical trials. The cost of broad MRI screening to identify those individuals with significant WMH, however, limits the feasibility of designing clinical trials which target WMH presence and which test treatments that slow progression. Hypothesis: A low-cost retinal or clinical screening measure prior to an MRI screening stage reduces the cost of recruiting persons with significant WMH burden in a hypothetical clinical trial vs an MRI-only screening design. Method: Data were from participants in the Atherosclerosis Risk in Communities-Neurocognitive study with clinical, retinal and WMH measurements ( N = 1311) at ages 53-70 years. Significant WMH burden was defined as a Cardiovascular Health Study score >2. Three low-cost pre-screening measures were assessed: (1) retinal: a score incorporating multiple markers of abnormal retinal vasculature, (2) clinical: a score incorporating hypertension, diabetes, and age, (3) combined retinal-clinical: a score incorporating retinal and clinical factors. Given a prior published target sample for a WMH clinical trial (N= 646), we calculated a theoretical screening sample size based on the proportion of each pre-screening measure in the population multiplied by the proportion of significant WMH burden among those with a prevalent pre-screening feature. Total recruitment cost was calculated using standard retinal ($32.50) and MRI ($650) cost estimates. Results: Compared to the estimated cost of MRI-only screening (>$4.24M, requiring MRI screening 6,526 participants), pre-screening for a high clinical score reduced total cost to $2.47M, but increased the initial screening group to 52,778 participants, of whom 3,801 would be screened by MRI). A high retinal-clinical score cutoff reduced costs to $2.9M while only requiring 13,572 screened participants (of these only 3,801 would require MRI). Conclusion: A 2-stage recruitment design with a low-cost pre-screening retinal and clinical measure is a promising approach, resulting in a reduction of theoretical recruitment costs for recruiting persons with significant WMH burden compared to an MRI-only design.

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.

Abstract Background Hearing loss is a risk factor for dementia; whether the association is causal or due to a shared pathology is unknown. We estimated the association of brain β-amyloid with hearing, hypothesizing no association. As a positive control, we quantified the association of hearing loss with neurocognitive test performance. Methods Cross-sectional analysis of Atherosclerosis Risk in Communities-Positron Emission Tomography study data. Amyloid was measured using global cortical and temporal lobe standardized uptake value ratios (SUVRs) calculated from florbetapir-positron emission tomography scans. Composite global and domain-specific cognitive scores were created from 10 neurocognitive tests. Hearing was measured using an average of better-ear air conduction thresholds (0.5–4 kHz). Multivariable-adjusted linear regression estimated mean differences in hearing by amyloid and mean differences in cognitive scores by hearing, stratified by race. Results In 252 dementia-free adults (72–92 years, 37% Black race, and 61% female participants), cortical or temporal lobe SUVR was not associated with hearing (models adjusted for age, sex, education, and APOE ε4). Each 10 dB HL increase in hearing loss was associated with a 0.134 standard deviation lower mean global cognitive factor score (95% CI: −0.248, −0.019), after adjustment for demographic and cardiovascular factors. Observed hearing-cognition associations were stronger in Black versus White participants. Conclusions Amyloid is not associated with hearing, suggesting that pathways linking hearing and cognition are independent of this pathognomonic Alzheimer’s-related brain change. This is the first study to show that the impact of hearing loss on cognition may be stronger in Black versus White adults.

Introduction: Hypertension in midlife, but not late life, is a robust predictor of subsequent dementia. However, the fraction of dementia attributable to hypertension might vary depending on the age of the population considered, and the age through which dementia onset occurs. Here, we investigated associations of hypertension assessed at various ages with incident dementia by age 80 or 90, then estimated population attributable fractions (PAF) for dementia from hypertension categories at each of these age groups. Hypothesis: Given hypertension prevalence increases with age but its relative risk for dementia tends to decrease, we had no prior expectation of the age at which the PAF’s would be highest. We hypothesized, however, that PAFs for incident dementia would be higher when hypertension is measured in midlife age groups versus late-life age groups. Methods: We leveraged 32 years of follow-up data from the Atherosclerosis Risk in Communities study (ARIC), a prospective, community-based cohort that enrolled participants aged 45-64 years from four US communities (Washington County, MD; Forsyth County, NC; Jackson, MS; and selected suburbs of Minneapolis, MI) at ARIC visit 1 (1987-1989). Participants were followed through 2018-2019. We used Cox proportional hazards models to estimate hazard ratios, then quantified PAFs, of dementia by age 80 and 90 from hypertension assessed at ages of 45-54 (ARIC visit 1), 55-64 (ARIC visits 1 and 4), 65-74 (ARIC visits 4 and 5), and 75-84 (ARIC visit 5). Results: Hypertension was assessed among 7,572 participants aged 45-54; 12,033 aged 55-64; and 6,561 aged 65-74. By age 80 the number identified as having incident dementia was 711, 910, and 372, respectively. Relative to normotension, hypertension in each age category was associated with hazard ratios (HRs) greater than 1.0 for dementia from hypertension by age 80. The PAF for dementia by age 80 from hypertension measured at age 45-54 was 15.3% (95% CI = 6.9, 22.3%), 19.1% (95% CI = 9.9, 26.9%) at ages 55-64, and 19.9% (95% CI = -4.4, 38.5%) at ages 65-74. By age 90, the number of incident dementia cases were 958; 2,302; and 1,327, respectively; and, among the 2,086 participants aged 75-84, 400 incident dementia cases. HRs were slightly smaller than those by age 80, while hypertension assessed in the 75-84 age group was not significant. The PAFs for dementia by age 90 from hypertension at age 45-54 was 13.8% (95% CI = 6.6, 20.0%), 12.9% (95% CI = 7.0, 18.2%) at ages 55-64, 10.9% (95% CI = 0.02, 21.0%) at ages 65-74, and non-significant at ages 75-84. Conclusions: Public health interventions targeting hypertension in midlife through early late-life might reduce a sizeable proportion of dementia cases.

AbstractINTRODUCTIONThe fraction of dementia attributable to hypertension might vary depending on the age of the population considered and the age through which dementia occurs.METHODSIn the Atherosclerosis Risk in Communities study, we quantified population attributable fractions (PAF) of dementia by age 80 and 90 from hypertension assessed at ages of 45–54 (n = 7572), 55–64 (n = 12,033), 65–74 (n = 6561), and 75–84 (n = 2086).RESULTSThe PAF for dementia by age 80 from all non‐normal blood pressure at ages 45–54 was 15.3% (95% confidence interval [CI] = 6.9%–22.3%), 19.1% (95% CI = 9.9%–26.9%) at ages 55–64, and 19.9% (95% CI = −4.4%–38.5%) at ages 65–74. The strongest PAFs were from stage 2 hypertension (11.9%–21.3%). For dementia by age 90, PAFs from non‐normal blood pressure up through age 75 were smaller (10.9%–13.8%), and non‐significant by age 75–84.DISCUSSIONInterventions targeting hypertension even in early late life might reduce a sizeable proportion of dementia.Highlights We estimated prospective population attributable risks of dementia for hypertension. 15%–20% of dementia cases by age 80 are from non‐normal blood pressure (BP). Associations between hypertension and dementia persisted through age 75. Midlife to early late‐life BP control might reduce a large proportion of dementia.

Abstract Hearing loss is a risk factor for dementia; whether this association differs by race is unknown. Although hearing loss is less prevalent in Blacks than Whites, we hypothesized the hearing loss-dementia relationship is stronger in Blacks. All-cause dementia and mild cognitive impairment (MCI) were adjudicated using longitudinal cognitive data. Hearing was measured using pure tone better-ear thresholds (0.5-4 kHz). Cox proportional hazards models adjusted for demographic and clinical covariates and included an interaction term between hearing and race. In 3,605 participants from a population-based cohort (68-89 years, 23% Black, 59% female), estimates for 7-year dementia risk per 10 decibels increase in hearing loss were stronger in Blacks (hazard ratio [HR]:1.24, 95% Confidence Interval (CI):1.07,1.43) than Whites (HR:1.07; 95%CI:0.96,1.19). Hearing loss is a risk factor for dementia in Black Americans. These findings emphasize the need to address existing racial disparities in hearing healthcare.

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.