Effect of Neurotoxin Exposure on Blood Biomarkers of Neurodegeneration and Alzheimer Disease.

AIM: To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology. METHODS: Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aß) 40 and Aß42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aß42/Aß40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome. RESULTS: In women, higher cadmium and lead levels were associated with higher baseline TTau concentrations. A higher baseline cadmium level was associated with lower baseline Aß42/Aß40 in both men and women. In age-sex-adjusted models, a doubling in baseline cadmium level was associated with a 0.2% (95% CI: 0.0, 0.3) higher increase per year in NfL concentrations. In men, a doubling of baseline lead level was associated with a 0.9% (95% CI: 0.1, 1.7) higher increase per year in TTau concentration. CONCLUSIONS: Participants with relatively higher levels of cadmium and lead had blood biomarker concentrations consistent with more neuronal damage and Alzheimer disease pathology. Environmental exposure to neurotoxins may contribute to neurodegeneration.

Age-associated changes in electroretinography measures in companion dogs.

PURPOSE: To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging. METHODS: Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinography was performed using a handheld device, with mydriasis and topical anaesthesia. Partial least squares effect screening analysis was performed to determine the effect of age, sex, body weight and use of anxiolytic medication on log-transformed ERG peak times and amplitudes; age and anxiolytic usage had significant effects on multiple ERG outcomes. Mixed model analysis was performed on data from dogs not receiving anxiolytic medications. RESULTS: In dogs not receiving anxiolytics, median age was 118 months (interquartile range 72-140 months, n = 77, 44 purebred, 33 mixed breed dogs). Age was significantly associated with prolonged peak times of a-waves (dark-adapted 3 and 10 cds/m2 flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01 cds/m2 flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.005) and b-waves (light-adapted 3 cds/m2 flash p < 0.0001, dark-adapted 0.01 cds/m2 flash p = 0.0004, 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.007) and flicker (light-adapted 30 Hz 3 cds/m2 p = 0.0004). Within the Golden Retriever breed, these trends were matched in a cross-sectional analysis of 6 individuals that received no anxiolytic medication. CONCLUSIONS: Aged companion dogs have slower and reduced amplitude responses in both rod- and cone-mediated ERG. Consideration of anxiolytic medication use should be made when conducting ERG studies in dogs.

Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

BACKGROUND: Age-related declines in cognitive function may begin in midlife. PURPOSE: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment. METHODS: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors. RESULTS: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/µL) were associated with 5-year cognitive decline. CONCLUSIONS: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

The Associations of Hearing Sensitivity and Different Cognitive Functions with Perception of Speech-in-Noise.

OBJECTIVES: Impaired speech-in-noise perception affects individuals' daily lives and is a frequent symptom of age-related hearing loss, which is a common disabling condition and a health concern in aging populations. The relative impact of hearing sensitivity loss and different cognitive functions on speech-in-noise perception is not well understood. We aimed to assess to what extent hearing sensitivity and different cognitive functions were associated with sentence-in-noise performance across the adult lifespan. DESIGN: This study is based on data of 2585 participants of the Rhineland Study, which is a German community-based cohort study of persons of age 30 years and older. We assessed speech-in-noise with a sentence-in-noise test (Göttinger Satztest), hearing sensitivity thresholds (air conduction pure-tone audiometry [PTA] average of 0.5, 1, 2, and 4 kHz), and the following cognitive domains: crystallized intelligence (German Mehrfachwahl-Wortschatz-Intelligenztest, MWT-B), executive functioning (Trail Making Test B, TMT), working memory (Digit Span forward, DS), and long-term memory (Verbal Learning and Memory Test delayed recall; VLMT). We examined the association between hearing sensitivity and cognitive functions with sentence-in-noise perception using a multivariable linear regression model adjusted for age, sex, and multiple potential confounders. RESULTS: Better hearing sensitivity was associated with better speech-in-noise perception (0.25 signal noise ratio [SNR] dB HL decrease per 5 dB HL decrease in PTA; 95% confidence interval [CI]: 0.20 to 0.25; p < 0.001). Better cognitive performance was also associated with better speech-in-noise perception, but to a lesser extent. Crystallized intelligence (MWT-B) showed an effect size of -0.10 SNR dB HL decrease per SD (95% CI: -0.14 to -0.06; p < 0.001), executive functioning (TMT) of -0.08 SNR dB HL decrease per SD (95% CI: -0.13 to -0.03; p = 0.002), working memory (DS) of -0.04 SNR dB HL decrease per SD (95% CI: -0.08 to -0.003; p = 0.03), and long-term memory (VLMT) of -0.03 SNR dB HL decrease per SD (95% CI: -0.07 to 0.01; p = 0.12). The standardized effect of hearing sensitivity (ß = 0.34) on speech-in-noise perception was four to five times larger than the effects of crystallized intelligence (ß = -0.08) and executive functioning (ß = -0.06). CONCLUSIONS: Hearing sensitivity was the strongest determinant of sentence-in-noise perception in adults above the age of 30. We determined the relative effect of different cognitive functions on sentence-in-noise perception. Crystallized intelligence and executive functions showed stronger associations while working and long-term memory functions had much smaller independent effects. Our results contribute to the understanding of determinants of speech-in-noise perception in aging adults.

The pupil constriction to light is associated with cognitive measures in middle-aged and older adults.

AIMS: The evidence relating the pupil light reflex (PLR) and cognition have been inconsistent. In this cross-sectional study, we evaluated the association between the PLR and cognition in community-dwelling middle-aged and older individuals. METHODS: Pupil reactivity was recorded in a subgroup of 403 participants (mean age 60.7 years, 57.3% females) in an epidemiologic study of aging. Ten pupil parameters were calculated to describe pupil constriction to light stimuli. A principal component analysis (PCA) score was used to calculate an overall performance over four cognitive testings. Linear regression was used to assess the association between pupil parameters and PCA scores, adjusting for age, sex, education, medications, health-related quality of life questionnaire, and systemic and ocular comorbidities. RESULTS: The PCA scores decreased by 0.039 [95% CI (- 0.050, - 0.028)] per year increase in age and were lower in males than females by 0.76 [95% CI (- 0.96, - 0.55)] (p < 0.001). Pupil constriction amplitude in millimeters and the duration from stimulus onset to maximal constriction velocity were significantly associated with cognition after adjusting for (1) age and sex and (2) age, sex, and multiple covariates (p < 0.05). CONCLUSIONS: In this study, we provided moderate evidence suggesting the association between PLR and neuropsychological cognitive measures. The findings suggest the potential of pupil reactivity to serve as a biomarker of brain aging and warrant further longitudinal study to assess if changes in the PLR can predict cognitive decline over time.

Factors Associated with the Macular Ganglion Cell-Inner Plexiform Layer Thickness in a Cohort of Middle-aged U.S. Adults.

SIGNIFICANCE: The macular ganglion cell-inner plexiform layer (mGCIPL) may serve as a quick and easily obtained measure of generalized neurodegeneration. Investigating factors associated with this thickness could help to understand neurodegenerative processes. PURPOSE: This study aimed to characterize and identify associated factors of the mGCIPL thickness in a Beaver Dam Offspring Study cohort of middle-aged U.S. adults. METHODS: Baseline examinations occurred from 2005 to 2008, with follow-up examinations every 5 years. Included participants had baseline data and measured mGCIPL at 10-year follow-up (N = 1848). The mGCIPL was measured using the Cirrus 5000 HD-OCT Macular Cube Scan. Associations between mean mGCIPL thickness and thin mGCIPL, defined as 1 standard deviation (SD) below the population mean, and baseline risk factors were investigated using generalized estimating equations. RESULTS: Participants (mean [SD] baseline age, 48.9 [9.3] years; 54.4% women) had mean (SD) mGCIPL thicknesses of 78.4 (8.1) µm in the right eye and 78.1 (8.5) µm in the left (correlation coefficient = 0.76). In multivariable models, age (-1.07 µm per 5 years; 95% confidence interval [CI], -1.28 to -0.86 µm), high alcohol consumption (-1.44 µm; 95% CI, -2.72 to -0.16 µm), higher interleukin 6 levels (50% increase in level: -0.23 µm; 95% CI, -0.45 to 0.00 µm), myopia (-2.55 µm; 95% CI, -3.17 to -1.94 µm), and glaucoma (-1.74 µm; 95% CI, -2.77 to -0.70 µm) were associated with thinner mGCIPL. Age (per 5 years: odds ratio [OR], 1.38; 95% CI, 1.24 to 1.53), diabetes (OR, 1.89, 95% CI, 1.09 to 3.27), myopia (OR, 2.11; 95% CI, 1.63 to 2.73), and increasing and long-term high C-reactive protein (ORs, 1.46 [95% CI, 1.01 to 2.11] and 1.74 [95% CI, 1.14 to 2.65], respectively) were associated with increased odds of thin mGCIPL. CONCLUSIONS: Factors associated cross-sectionally with mGCIPL thickness, older age, high alcohol consumption, inflammation, diabetes, myopia, and glaucoma may be important to neural retina structure and health and neuronal health system-wide.

Midlife sensory and motor functions improve prediction of blood-based measures of neurodegeneration and Alzheimer's disease in late middle-age.

INTRODUCTION: We assessed whether midlife sensory and motor functions added to prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS) improve risk predictions of 10-year changes in biomarkers of neurodegeneration and Alzheimer's disease. METHODS: Longitudinal data of N = 1529 (mean age 49years) Beaver Dam Offspring Study participants from baseline, 5-year, and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function measures improves CAIDE or FRS risk predictions of 10-year incidence of biomarker positivity of serum-based neurofilament light chain (NfL) and amyloid beta (Aß)42/Aß40 using logistic regression. RESULTS: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved NfL and Aß42/Aß40 positivity predictions in adults above the age of 55. DISCUSSION: Including midlife sensory and motor function improved long-term biomarker positivity predictions. Non-invasive sensory and motor assessments could contribute to cost-effective screening tools that identify individuals at risk for neurodegeneration early to target interventions and preventions. Highlights: Sensory and motor measures improve risk prediction models of neurodegenerative biomarkersSensory and motor measures improve risk prediction models of AD biomarkersPrediction improvements were strongest in late midlife (adults >55 years of age)Sensory and motor assessments may help identify high-risk individuals early.

Midlife sensory and motor functions improve long-term predictions of cognitive decline and incidence of cognitive impairment.

INTRODUCTION: We aimed to assess whether midlife sensory and motor functions improve risk prediction of 10-year cognitive decline and impairment when added to risk prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS). METHODS: Longitudinal data of N = 1529 (mean age 49 years; 54% women) Beaver Dam Offspring Study (BOSS) participants from baseline, 5 and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk predictions of 10-year cognitive decline or cognitive impairment incidence using logistic regressions. RESULTS: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved areas under the curve for cognitive decline and impairment models. DISCUSSION: Including midlife sensory and motor function improved risk predictions of long-term cognitive decline and impairment in middle-aged to older adults. Sensory and motor assessments could contribute to cost-effective and non-invasive screening tools that identify high-risk individuals earlier to target intervention and prevention strategies. Highlights: Sensory and motor measures improve risk prediction models of cognitive decline.Sensory and motor measures improve risk prediction models of cognitive impairment.Prediction improvements were strongest in midlife (adults < 55 years of age).Sensory and motor changes may help identify high-risk individuals early.

Associations of Dietary Intake With Self-Reported Hearing Loss: Findings From the Survey of the Health of Wisconsin.

PURPOSE: The purpose of this study was to evaluate associations of dietary intake components with hearing loss. METHOD: Participants were from the population-based Survey of the Health of Wisconsin. The Block food frequency questionnaire measured dietary intake of carbohydrates, fiber, protein, free (added) sugars, fruits, vegetables, saturated and trans fats, and glycemic index. Intake was categorized into quintiles (Q). Hearing loss was self-reported. Logistic regression models were used to evaluate associations of dietary determinants with hearing loss. Results are presented as odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Final models were adjusted for age, sex, total energy intake, race/ethnicity, education, smoking, and regular physical activity. RESULTS: There were 2,839 participants (56% women; Mage = 48.2 [SD = 14.5] years) included. Higher consumption of trans fat (Q5: OR = 1.83, 95% CI [1.27, 2.64]) and higher glycemic index (Q5: OR = 1.34, 95% CI [1.00, 1.80]) were associated with increased odds of hearing loss. Hearing loss was associated with fruit, saturated- and trans-fat intake in women, and trans-fat intake and glycemic index in men. CONCLUSIONS: Dietary intake was associated with self-reported hearing loss. Research on mechanistic pathways of associations and public health interventions to prevent hearing loss is needed.

Lifestyle and factors of vascular and metabolic health and inflammation are associated with sensorineural-neurocognitive aging in older adults.

This study's aim was to identify risk factors associated with sensorineural and neurocognitive function (brain aging) in older adults. In N = 1,478 Epidemiology of Hearing Loss Study participants (aged 64-100 years, 59% women), we conducted sensorineural and cognitive tests, which were combined into a summary measure using Principal Component Analysis (PCA). Participants with a PCA score <-1 standard deviation (SD) were considered to have brain aging. Incident brain aging was defined as PCA score <-1 SD at 5-year follow-up among participants who had a PCA score ≥-1 SD at baseline. Logistic regression and Poisson models were used to estimate associations between baseline risk factors of lifestyle, vascular and metabolic health, and inflammation and prevalent or incident brain aging, respectively. In an age-sex adjusted multivariable model, not consuming alcohol (odds ratio(OR) = 1.77, 95% confidence Interval (CI) = 1.18,2.66), higher interleukin-6 levels (OR = 1.30, 95% CI = 1.03,1.64), and depressive symptoms (OR = 2.44, 95% CI = 1.63,3.67) were associated with a higher odds of having brain aging, while higher education had protective effects (OR = 0.55, 95% CI = 0.33,0.94). A history of stroke, arterial stiffness, and obesity were associated with an increased risk of developing brain aging during the five years of follow-up. Lifestyle, vascular, metabolic and inflammatory factors were associated with brain aging in older adults, which adds to the evidence of shared pathways for sensorineural and neurocognitive declines in aging. Targeting these shared central processing etiological factors with interventions may lead to retention of better neurological function, benefiting multiple systems, i.e., hearing, smell, and cognition, ultimately helping older adults retain independence and higher quality of life longer.

Association of Central Retinal Arteriolar and Venular Equivalents with Brain-aging and Macular Ganglion Cell-inner Plexiform Layer Thickness.

INTRODUCTION: Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration. METHODS: Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005-2008) age 21-84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010-2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015-2017, were also investigated. RESULTS: Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively. DISCUSSION: The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.

Associations of Midlife Lifestyle and Health Factors with Long-Term Changes in Blood-Based Biomarkers of Alzheimer's Disease and Neurodegeneration.

BACKGROUND: Pathological biomarkers of Alzheimer's disease (AD) and other dementias can change decades before clinical symptoms. Lifestyle and health factors might be relevant modifiable risk factors for dementia. Many previous studies have been focusing on associations of lifestyle and health-related factors with clinical outcomes later in life. OBJECTIVE: We aimed to determine to what extent midlife factors of lifestyle, inflammation, vascular, and metabolic health were associated with long-term changes in blood-based biomarkers of AD (amyloid beta (Aß)) and neurodegeneration (neurofilament light chain (NfL); total tau(TTau)). METHODS: In 1,529 Beaver Dam Offspring Study (BOSS) participants (mean age 49 years, standard deviation (SD) = 9; 54% were women), we applied mixed-effects models with baseline risk factors as determinants and 10-year serum biomarker change as outcomes. RESULTS: We found that education and inflammatory markers were associated with levels and/or change over time across all three markers of AD and neurodegeneration in the blood. There were baseline associations of measures of cardiovascular health with lower Aß42/Aß40. TTau changed little over time and was higher in individuals with diabetes. Individuals with lower risk in a number of cardiovascular and metabolic risk factors, including diabetes, hypertension, and atherosclerosis had slower accumulation of neurodegeneration over time, as determined by NfL levels. CONCLUSION: Various lifestyle and health factors, including education and inflammation, were associated with longitudinal changes of neurodegenerative and AD biomarker levels in midlife. If confirmed, these findings could have important implications for developing early lifestyle and health interventions that could potentially slow processes of neurodegeneration and AD.

Psychological distress and well-being among sensory impaired individuals during COVID-19 lockdown measures.

PURPOSE: Hearing and vision impairment are prevalent chronic conditions associated with poorer mental health. Limitations of in-person contacts during COVID-19-related lockdown measures may affect those with sensory impairments more severely exacerbating mental health problems. We aimed to determine whether hearing and/or visual impairment were associated with more psychological distress during a time of lockdown measures in Spring/Summer 2020 in Wisconsin. METHODS: We included 1341(64% women, aged 20-92 years) Survey of the Health of Wisconsin COVID-19 survey participants (May 2020-July,2020). We assessed self-reported current mental health and well-being and vision and hearing impairment. Logistic regression models with sensory impairments as determinants and mental health outcomes were adjusted for age, gender, race, education, heart disease, hypertension, hyperlipidemia, and diabetes. RESULTS: Vision impairment was associated with increased odds of generalized anxiety disorder (odds ratio = 2.10; 95% confidence interval = 1.32-3.29) and depressive symptoms (2.57;1.58-4.11), greater likelihood to report loneliness (1.65;1.00-2.64) and hopelessness (1.45;1.01-2.08). Hearing impaired individuals reported more loneliness (1.80;1.05-2.98) and hopelessness (1.42;0.99-2.03). Exploratory analyses revealed that sensory impaired individuals less often chose walking as a coping strategy during the pandemic. CONCLUSIONS: Individuals with sensory impairment may represent a particularly vulnerable population during the COVID-19 pandemic. Future research should determine underlying reasons and interventions to mitigate this populations' disadvantages.

Subjective vision assessment in companion dogs using dogVLQ demonstrates age-associated visual dysfunction.

Introduction: Dim light vision as assessed by proxy and clinical tools is commonly impaired in older humans and impacts quality of life. Although proxy visual assessment tools have been developed for dogs, it is unclear if they are sensitive enough to detect subtle visual dysfunction in older dogs. We sought to determine if a newly designed proxy visual function questionnaire could detect age-associated differences in visual behaviors in varying lighting conditions in dogs. Methods: A 27-item questionnaire (the dog variable lighting questionnaire, dogVLQ) was designed to assess visual behavior in dogs in different lighting settings. We conducted the dogVLQ, a previously validated visual function questionnaire the dog vision impairment score and performed light- and dark-adapted electroretinography (ERG) on a subset of dogs. Questionnaire scores were analyzed for dog age associations using correlation analysis. Results: Questionnaire responses from 235 dog owners were obtained (122 female, 112 male dogs), 79 of which underwent ERG (43 female, 36 male dogs). Bright light visual behavior was significantly associated with light-adapted bright flash ERG amplitudes, visual behavior in near darkness was associated with dark-adapted ERG amplitudes. The dogVLQ identified worse vision in older dogs in bright light, dim light, and darkness; predicted onset was younger for vision in near darkness. Older dogs had more difficulty navigating transitions between lighting conditions. Discussion: Subjective dog owner assessment of visual function associates with objective measurement of retinal function in dogs and supports reduced vision-mediated behaviors in older dogs.

Associations of Hearing Loss and Hearing Aid Use With Cognition, Health-Related Quality of Life, and Depressive Symptoms.

ObjectivesDetermine associations of hearing loss (HL) and hearing aid (HA) use with cognition, health-related quality of life (HRQoL), and depressive symptoms. Methods: Participants were from the Epidemiology of Hearing Loss Study or Beaver Dam Offspring Study. HL was defined as pure-tone average (.5-4.0 kHz) > 25 dB. A principal component analysis of 5 cognitive tasks measured cognition. The SF-12 measured mental and physical HRQoL. The Centers for Epidemiological Studies Depression Scale measured depressive symptoms (score ≥ 16). Regression models returned beta (B) coefficients or odds ratios (OR) with 95% confidence intervals. Results: This study included 3574 participants. HL (vs. none) was associated with poorer cognition (B-.12 [-.18, -.06]), mental (B-.99 [-1.65, -.33]) and physical (B-.76 [-1.50, -.03]) HRQoL, and increased odds of depressive symptoms (OR 1.49 [1.16, 1.91]). HA users had better cognition than non-users. Discussion: HL likely impacts cognition and well-being. HA use may have cognitive benefits.

Better cognitive function in younger generations - Insights from two cohort studies of middle-aged to older adults in Wisconsin.

BACKGROUND: Understanding generational trends in dementia and cognitive decline is essential to quantify future healthcare needs and may help identify interventions and preventions. We aimed to determine whether individuals from more recent generations showed better neurocognitive function. METHODS: This cross-sectional study combined data from 4439 participants (mean age 64 years (SD = 13); 57% were women) from the Epidemiology of Hearing Loss Study and Beaver Dam Offspring Study. We assessed participants' birth cohort (1901-1924, Greatest Generation; 1925-1945, Silent Generation; 1946-1964, Baby Boom Generation; 1965-1984, Generation X) and neurocognition (Trail-Making Tests A and B, Digit Symbol Substitution Test, Auditory Verbal Learning Test, Verbal Fluency Test). Multivariable linear regression models were utilized. RESULTS: Adjusted for age, sex, education, and known risk factors for cognitive decline, more recent generations showed better processing speed, executive function, attention, and verbal fluency than the Greatest Generation. Largest benefits were found in the Baby Boom Generation. Compared with the Greatest Generation, individuals from the Baby Boom Generation performed better on Trail-Making Tests A (-0.21 ln(time in s); 95% confidence interval (CI) -0.29, -0.13) and B (-0.31 ln(time in s); 95% CI -0.40, -0.22), Digit Symbol Substitution Test (6.07 numbers correct; 95% CI 3.61, 8.52) and Verbal Fluency Test (8.75 numbers correct; 95% CI 5.07, 12.42 in women; 5.28 numbers correct; 95% CI 0.79, 9.78 in men), with effect sizes similar to effects of 11-15 years of less aging. CONCLUSIONS: This indicates that some benefits of younger generations might be related to yet unknown and potentially modifiable environmental, health-related or lifestyle factors and motivates research of such underlying factors to promote healthy cognitive aging.

Prevalence of Self-Reported Hearing Loss and Associated Risk Factors: Findings From the Survey of the Health of Wisconsin.

PURPOSE: The purpose of this study was to determine the prevalence of self-reported hearing loss and associated risk factors in a representative population-based study of Wisconsin residents. METHOD: Survey of the Health of Wisconsin participants with data on self-reported hearing loss were included. We reported prevalence of self-reported hearing loss with corresponding 95% confidence intervals (CIs), overall, and stratified by age and sex. Age- and sex-adjusted and multivariable logistic regression models were used to evaluate determinants of self-reported hearing loss, and results are presented as odds ratios with corresponding 95% CIs. RESULTS: There were 2,767 participants (50.7% men) with a mean age of 46 years (range: 21-74) in this study. Prevalence of self-reported hearing loss was 26.8% (24.4, 28.4) and was higher in men (30.3% [27.1, 33.4]) than in women (22.5% [19.9, 25.0]). Prevalence increased with age. After multivariable adjustment, age (per +1 year increase; 1.05 [1.04, 1.06]), male sex (1.57 [1.18, 2.08]), having two chronic diseases (vs. 0; 1.93 [1.16, 3.23]), occupational (2.47 [1.91, 3.19]) and recreational (1.58 [1.22, 2.04]) noise exposure, and poor diet (1.88 [1.28, 2.78]) were associated with higher odds of self-reported hearing loss. CONCLUSIONS: Hearing loss is a highly prevalent public health concern and may be at least partially modifiable via interventions to reduce noise exposure and promote health. Statewide prevalence and risk factor data can be used to inform public health practice and promote hearing loss prevention. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19661130.

Effect of Long-Term Storage on the Reliability of Blood Biomarkers for Alzheimer's Disease and Neurodegeneration.

BACKGROUND: Stored blood samples from longitudinal cohort studies may be useful for studying biomarkers of preclinical Alzheimer's disease. OBJECTIVE: This study aimed to determine the reliability of amyloid-ß40 and amyloid-ß42 (Aß40, Aß42), total tau (TTau), and neurofilament light (NfL) concentrations measured in blood samples stored long-term at -80°C. METHODS: Aß40, Aß42, TTau, and NfL were measured in serum and plasma samples from two longitudinal cohort studies. Serum samples had been stored at -80°C for 5 (n = 24), 14 (n = 24), and 20 years (N = 78) and plasma samples had been stored for 16 years (N = 78). Biomarker concentrations were measured in duplicate using a single molecule array assay (Simoa; Quanterix, Billerica, MA). Replicate samples for each sample type and storage length were included. RESULTS: The concentrations of Aß40, Aß42, TTau, and NfL were within expected ranges. Some serum TTau concentrations were below the limit of detection. The average intra-assay coefficients of variation (CV) for duplicate measures were 2-7% for all assays except for serum TTau, which were higher (CVs 13% and 17%). Mean differences in original replicate pair Aß40, Aß42, and NfL concentrations were slightly greater in samples stored for longer versus shorter time periods. CONCLUSION: Aß40, Aß42, TTau, and NfL can be measured in serum and plasma samples that have been stored up to 20 years at -80°C. Long-term storage may be associated with small increases in the variability of concentrations in samples stored 14 or more years.

Associations of sensory and motor function with blood-based biomarkers of neurodegeneration and Alzheimer's disease in midlife.

Pathological biomarkers of dementia and Alzheimer's disease (AD) change decades before clinical symptoms. Common sensory and motor changes in aging adults may be early markers of neurodegeneration. We investigated if midlife sensory and motor functions in Beaver Dam Offspring Study (BOSS) participants (N = 1529) were associated with longitudinal changes in blood-based biomarkers of neurodegeneration (neurofilament light chain (NfL); total tau (TTau)) and AD (amyloid beta (Aß)). Mixed-effects models with baseline sensory and motor function as determinants and 10-year biomarker change as outcome were used. Participants with hearing impairment and worse motor function (among women) showed faster increases in NfL level over time (0.8% per year; 0.3% per year, respectively). There were no significant associations with TTau or Aß. We found consistent relationships between worse baseline hearing and motor function with a faster increase in neurodegeneration, specifically serum NfL level. Future studies with longer follow-up should determine if sensory and motor changes are more reflective of general neurodegeneration than AD-specific pathology and whether sensory and motor tests may be useful screening tools for neurodegeneration risk.

The Association of Psychological Well-Being With Sensory and Cognitive Function and Neuronal Health in Aging Adults.

OBJECTIVES: Psychological well-being (PWB) may be a potential modifiable risk factor of age-related diseases. We aimed to determine associations of PWB with sensorineural and cognitive function and neuronal health in middle-aged adults. METHODS: This study included 2039 Beaver Dam Offspring Study participants. We assessed PWB, hearing, visual acuity, contrast sensitivity impairment, olfactory impairment, cognition, and retinal (macular ganglion cell inner-plexiform layer, mGCIPL) thickness. Age-sex-education-adjusted multivariable linear, logistic regression, and generalized estimating equation models were used and then further adjusted for health-related confounders. RESULTS: Individuals with higher PWB had better hearing functions, visual acuity, and thicker mGCIPL and reduced odds for hearing, contrast sensitivity and olfactory impairment in age-sex-education-adjusted models. Effects on mGCIPL and visual and olfactory measures decreased with adjustment. Higher PWB was associated with better cognition, better combined sensorineural-cognitive function, and decreased cognitive impairment. DISCUSSION: Psychological well-being was associated with sensorineural-cognitive health indicating a potential of PWB interventions for healthy aging.