Deal, Jennifer A.

AbstractBackgroundAlthough both age‐related and highly prevalent, little is known regarding the prevalence of hearing loss among persons with dementia (PwD). Current understanding is based on convenience samples primarily from specialized memory clinics. The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS) is a large, prospective study of a population‐based cohort from 4 U.S. community sites with audiometric and neurocognitive testing and bi‐racial representation. We examined the prevalence of hearing loss and hearing aid use among older adults with cognitive impairment and whether cognitive status influences hearing aid use.MethodWe analyzed audiometric and hearing care data from ARIC‐NCS Visit 6 (2016‐2018). Participants underwent a full neurocognitive battery and audiometric evaluation at Visit 6. Participants with complete audiometric data and an adjudicated diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia were included in the analytical cohort (N=3,385). Differences in participant characteristics by cognitive status were descriptively compared using Chi‐square tests or one‐way ANOVAs. We performed a series of logistic regression models to estimate the odds of hearing aid non‐use by cognitive status.ResultPrevalence of hearing loss was greater with increasing cognitive impairment (cognitively normal:64.7%; MCI:71.3%; dementia:83.3%). Prevalence of hearing aid use among those with hearing loss and cognitive impairment varied by race (African Americans 7.2%; whites 32.8%). In a multivariable‐adjusted model, cognitive impairment was independently associated with higher odds of non‐use of hearing aids (MCI odds ratio (OR):1.4 (95%CI:1.0‐1.8); dementia OR:1.8 (95%CI:1.2‐2.9) versus cognitively normal). The strongest risk factor for non‐use of hearing aids was race, where African Americans have almost a 5 times higher odds of not using hearing aids compared to whites (95% CI:2.9‐7.4).ConclusionHearing loss is highly prevalent but vastly untreated among older adults with cognitive impairment, particularly African Americans, and cognitive impairment is independently associated with hearing aid use. These estimates are some of the first population‐based estimates of audiometric hearing loss among diverse older adults with adjudicated diagnoses of MCI or dementia. With increased calls to address ethnic/racial disparities, we must include hearing loss, as one of the most common co‐morbidities, in order to optimize health and well‐being among all PwD.

AbstractIntroductionAs hearing loss has been identified as an important risk factor for dementia, we aimed to assess the association between hearing loss and microstructural integrity of the brain.MethodsA total of 1086 dementia‐free participants (mean age = 75.2 [standard deviation: 4.9], 61.4% female) of the population‐based Atherosclerosis Risk in Communities (ARIC) study underwent hearing assessment (2016–2017) and magnetic resonance imaging of the brain (2011–2013). Microstructural integrity was determined with diffusion tensor imaging. Multivariable linear regression was used to investigate associations between hearing loss and microstructural integrity of different brain regions and white matter (WM) tracts.ResultsHearing loss was associated with lower WM microstructural integrity in the temporal lobe, lower gray matter integrity of the hippocampus, and with lower WM microstructural integrity of the limbic tracts and the uncinate fasciculus.ConclusionOur results demonstrate that hearing loss is indepedently associated with lower microstructural integrity in brain regions that are important for different cognitive processes.

Introduction: Cerebrovascular small vessel disease, seen on brain imaging as lacunes and white matter hyperintensities (WMH), is a substrate for dementia in older adults. Diffusion tensor imaging (DTI) is thought to provide early signs of loss of white matter (WM) integrity due to microvascular disease and predicts WM hyperintensity volume. Retinal fundus photography provides surrogate measures of cerebral microvasculature. No studies have quantified the long-term association between retinal signs and DTI measures. Hypothesis: Microvascular retinal signs measured in midlife are associated with small vessel disease measured on brain magnetic resonance imaging (MRI) 18 years later, including reduced WM microstructural integrity (lower fractional anisotrophy [FA] and greater mean diffusivity [MD] by DTI), greater WM hyperintensity volume and greater lacune prevalence. Methods: In a biracial prospective cohort study, retinal signs were measured using fundus photography (1993-1995) with 3-T magnetic resonance imaging conducted in 2011-13. Multivariable-adjusted linear regression was used to quantify the relationships of retinal signs with WM measures. Prevalence of lacunar infarcts by retinal sign status was estimated using log binomial regression. Analyses were adjusted for age [linear and quadratic terms], education, sex, race, intracranial volume, body mass index, smoking, diabetes, hypertension, and ≥1 APOE ε4 alleles. Results: In 1829 men and women (60% [N=1100] female, 27% [N=489] black race, aged 50-72 years when retinal signs were measured), a binary measure comprised of two retinal signs suggestive of arteriolar damage due to hypertension (focal arteriolar narrowing and/or arteriovenous nicking) was associated with worse (lower) FA (standardized β=-0.19, 95% confidence interval [CI]=-0.35, -0.02), worse (higher) MD (β=0.15, 95% CI=0.00, 0.30), greater WM hyperintensity volume (β=0.15, 95% CI=0.01, 0.30), and greater prevalence of lacunes (prevalence ratio=1.33, 95% CI: 0.99, 1.80). Generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles) was associated with worse FA (β=-0.13, 95% CI=-0.24, -0.01) and worse MD (β=0.12, 95% CI=0.01, 0.23). Results did not differ by sex, race, hypertension status or APOE ε4 genotype. No associations were found for retinopathy, but only 56 participants had retinopathy. Conclusions: Consistent with prior work, and as expected based on a common underlying pathology, retinal signs predicted WM disease and lacunar infarcts 18 years later. Novel to this study, we found that retinal signs related to arteriolar damage also predicted loss of white matter microvascular integrity measured using DTI.

Purpose The purpose of this study was to investigate associations between performance on a clinical speech-in-noise measure with a comprehensive neurocognitive battery of tests. Method A group of older adults ( N = 250, M age = 77 years, age range: 67.3–89.1 years) enrolled in the Atherosclerosis Risk in Communities Neurocognitive Study took part in the hearing pilot study (2013) that included testing for audiometric thresholds and speech-in-noise performance (Quick Speech-in-Noise Test; Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004). This research study analyzed the associations between domain-specific cognitive function and speech-in-noise performance after adjusting for hearing thresholds and other demographic and cardiovascular factors. Results Multivariable-adjusted associations were found between all cognitive domains and speech-in-noise performance in the full sample, but the observed associations varied when participants with varying levels of moderate to moderately severe hearing loss were excluded from the analysis. Conclusions The findings are discussed in terms considering the cognitive status of older adults in relation to their speech-in-noise performance during audiological evaluation and implications for aural rehabilitation.

Abstract Although APOE ε4 is an established risk factor for dementia, it is unclear whether it is associated with elevated risk or earlier symptom onset. Longitudinal study of 10,400 white-race individuals in the ARIC cohort followed from age 60 to incident dementia diagnosis, death, or censoring. All-cause dementia was defined using standardized algorithms incorporating longitudinal cognitive change, proxy report, and hospital or death certificate dementia codes. Death was ascertained via the National Death Index and death certificates. We used a parametric mixture of generalized gamma distributions to simultaneously estimate the distribution of event times and the proportion of individuals who experience each outcome (i.e., dementia and its competing risk, dementia-free death) by APOE ε4 status (≥ 1 allele vs. no alleles). Age-adjustment was through use of age as the time scale. APOE ε4 carrier status was associated with a doubling of the overall frequency of dementia incidence to 25% compared to 13% (p < 0.001) in non- ε4 carriers. The distributions of time to dementia was modified by APOE ε4 status (p=0.007): median time to dementia onset among APOE ε4 carriers was 81.9 years compared to 83.3 years in non-APOE ε4 carriers (p = 0.005). No differences in results were found by sex. APOE ε4 carrier status is associated with both elevated risk and earlier time to dementia onset. These findings clarify the causal role of APOE in dementia etiology, could help better identify at-risk subgroups, and may help facilitate better research recruitment.

Background Central arterial stiffening and increased pulsatility, with consequent cerebral hypoperfusion, may result in structural brain damage and cognitive impairment. Methods and Results We analyzed a cross‐sectional sample of ARIC ‐ NCS (Atherosclerosis Risk in Communities–Neurocognitive Study) participants (aged 67–90 years, 60% women) with measures of cognition (n=3703) and brain magnetic resonance imaging (n=1255). Central arterial hemodynamics were assessed as carotid‐femoral pulse wave velocity and pressure pulsatility (central pulse pressure). We derived factor scores for cognitive domains. Brain magnetic resonance imaging using 3‐Tesla scanners quantified lacunar infarcts; cerebral microbleeds; and volumes of white matter hyperintensities, total brain, and the Alzheimer disease signature region. We used logistic regression, adjusted for demographics, apolipoprotein E ɛ4, heart rate, mean arterial pressure, and select cardiovascular risk factors, to estimate the odds of lacunar infarcts or cerebral microbleeds. Linear regression, additionally adjusted for intracranial volume, estimated the difference in log‐transformed volumes of white matter hyperintensities , total brain, and the Alzheimer disease signature region. We estimated the mean difference in cognitive factor scores across quartiles of carotid‐femoral pulse wave velocity or central pulse pressure using linear regression. Compared with participants in the lowest carotid‐femoral pulse wave velocity quartile, participants in the highest quartile of carotid‐femoral pulse wave velocity had a greater burden of white matter hyperintensities ( P =0.007 for trend), smaller total brain volumes (−18.30 cm 3 ; 95% CI , −27.54 to −9.07 cm 3 ), and smaller Alzheimer disease signature region volumes (−1.48 cm 3 ; 95% CI , −2.27 to −0.68 cm 3 ). These participants also had lower scores in executive function/processing speed (β=−0.04 z score; 95% CI , −0.07 to −0.01 z score) and general cognition (β=−0.09 z score; 95% CI , −0.15 to −0.03 z score). Similar results were observed for central pulse pressure . Conclusions Central arterial hemodynamics were associated with structural brain damage and poorer cognitive performance among older adults.

AbstractIntroductionThe easily‐imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia.MethodsIn a population‐based study of 12,482 adults aged 50‐73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993‐1995) with incident all‐cause dementia (1993‐1995 to 2011‐2013) and with etiologic subtype of dementia/mild cognitive impairment (2011‐13).ResultsA total of 1259 (10%) participants developed dementia over a mean 15.6 years. Moderate/severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.36–2.55) and central retinal arteriolar equivalent (narrowest quartile vs. widest three quartiles; HR, 1.26; 95% CI: 1.09–1.45) were associated with all‐cause dementia. Results were qualitatively stronger (but not statistically significantly different) in participants with diabetes. Retinopathy was associated with a joint outcome of cerebrovascular‐related, but not Alzheimer's disease–related, dementia/mild cognitive impairment (HR, 2.29; 95% CI: 1.24–4.23).DiscussionExploration of measures in the eye may provide surrogate indices of microvascular lesions relevant to dementia.

Abstract Introduction We tested the hypotheses that higher levels of and persistence of midlife leisure‐time physical activity (LTPA) are associated long‐term with lower cognitive decline and less incident dementia. Methods A total of 10,705 participants (mean age: 60 years) had LTPA (no, low, middle, or high) measured in 1987‐1989 and 1993‐1995. LTPA was assessed in relation to incident dementia and 14‐year change in general cognitive performance. Results Over a median follow‐up of 17.4 years, 1063 dementia cases were observed. Compared with no LTPA, high LTPA in midlife was associated with lower incidence of dementia (hazard ratio [95% confidence interval], 0.71 [0.61, 0.86]) and lower declines in general cognitive performance (−0.07 standard deviation difference [−0.12 to −0.04]). These associations were stronger when measured against persistence of midlife LTPA over 6 years. Discussion LTPA is a readily modifiable factor associated inversely with long‐term dementia incidence and cognitive decline.

AbstractIntroductionWe tested the hypothesis that poor sense of smell is associated with lower cognitive function and higher mild cognitive impairment (MCI) prevalence.MethodsOlfaction, measured by the Sniffin' Sticks test, was categorized as olfactory impairment (OI) (score ≤6) or no OI (score >6). MCI was adjudicated based on review of a neuropsychological examination. Linear regression estimated the mean difference in cognitive factor scores, and log‐binomial regression quantified MCI prevalence among participants with versus without OI.ResultsParticipants with OI had lower mean factor scores (memory: −0.27 standard deviation [SD], 95% confidence interval [CI]: −0.35 to −0.19; language: −0.24 SD, 95% CI: −0.30 to −0.17; executive function/processing speed: −0.09 SD, 95% CI: −0.12 to −0.06; and general cognitive performance: −0.25 SD, 95% CI: −0.30 to −0.20). OI was also associated with MCI (n = 204; prevalence ratio = 1.56, 95% CI: 1.37, 1.78).DiscussionAn impaired sense of smell may serve as a readily accessible early marker of neurodegeneration and improve upon the prevailing delayed diagnoses and underascertainment of MCI/dementia.