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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.
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Doença de Alzheimer , Masculino , Humanos , Feminino , Doença de Alzheimer/patologia , Chumbo , Peptídeos beta-Amiloides , Neurotoxinas , Cádmio , Proteínas tau , BiomarcadoresRESUMO
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.
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Disfunção Cognitiva , Neurotoxinas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inflamação/epidemiologia , Estudos Longitudinais , Disfunção Cognitiva/epidemiologia , Biomarcadores , Fatores de RiscoRESUMO
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.
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Cognição/fisiologia , Pupila/fisiologia , Reflexo Pupilar , Fatores Etários , Idoso , Constrição , Estudos Transversais , Feminino , Humanos , Luz , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Qualidade de Vida , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
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.
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Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de Risco , Tomografia de Coerência Óptica , Adulto JovemRESUMO
BACKGROUND: Relationships between brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present). METHODS: Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. BDNF, IGF-1, and aldosterone were measured in serum collected in 1998 to 2000. RESULTS: There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low BDNF was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low BDNF was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline. CONCLUSION: Low levels of serum BDNF and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.
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Envelhecimento/fisiologia , Biomarcadores/sangue , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Fatores de Proteção , Idoso , Aldosterona/análise , Aldosterona/sangue , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/sangue , Feminino , Humanos , Fator de Crescimento Insulin-Like I/análise , Estudos Longitudinais , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Estudos Prospectivos , Estados UnidosRESUMO
OBJECTIVES: The Dichotic Digits test (DDT) has been widely used to assess central auditory processing but there is limited information on observed DDT performance in a general population. The purpose of the study was to determine factors related to DDT performance in a large cohort spanning the adult age range. DESIGN: The study was cross-sectional and subjects were participants in the Epidemiology of Hearing Loss Study (EHLS), a population-based investigation of age-related hearing loss, or the Beaver Dam Offspring Study (BOSS), a study of aging in the adult offspring of the EHLS members. Subjects seen during the 4th EHLS (2008 to 2010) or the 2nd BOSS (2010 to 2013) examination were included (N = 3655 participants [1391 EHLS, 2264 BOSS]; mean age = 61.1 years, range = 21 to 100 years). The free and right ear-directed recall DDTs were administered using 25 sets of triple-digit pairs with a 70 dB HL presentation level. Pure-tone audiometric testing was conducted and the pure-tone threshold average (PTA) at 0.5, 1, 2, and 4 kHz was categorized using the worse ear: no loss = PTA ≤ 25 dB HL; mild loss = 25 < PTA ≤ 40 dB HL; moderate or marked loss = PTA > 40 dB HL. Cognitive impairment was defined as a Mini-Mental State Examination score < 24 (maximum = 30) or a self- or proxy-reported history of dementia or Alzheimer's disease. Demographic information was self-reported. General linear models were fit and multiple linear regression was performed. RESULTS: The mean total free recall DDT score was 76.7% (range = 21.3 to 100%). Less than 10% of the participants had a total free recall score below 60% correct. The mean right ear-directed recall score was 98.4% with 69% of the participants scoring 100% and another 15.5% scoring 98.7% (1 incorrect digit). In multivariable modeling of the total free recall scores, the predicted mean free recall score was 1 percentage point lower for every 5-year increase in age, 2.3 percentage points lower in males than females, 8.7 percentage points lower in participants with less than a high school degree than in those with college degrees, 6.8 percentage points lower in participants with a moderate or marked hearing loss compared with no hearing loss, and 8.3 percentage points lower in participants with cognitive impairment compared with those without cognitive impairment. These 5 factors were independently and significantly related to performance and accounted for 22.7% of the total variability in free recall scores. CONCLUSIONS: Substantial variation in the total free recall DDT scores but very little variation in the right ear-directed recall DDT scores was observed. Age, sex, education, hearing loss severity, and cognitive impairment were found to be significantly related to DDT scores but explained less than 25% of the total variability in total free recall scores. The right ear-directed recall DDT by itself may not be of benefit in assessing central auditory processing in a general population because of its limited variability but further evaluation of factors potentially related to free recall DDT variability may prove useful.
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Percepção Auditiva , Testes com Listas de Dissílabos , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Audiometria de Tons Puros , Estudos de Coortes , Estudos Transversais , Estudos Epidemiológicos , Feminino , Transtornos da Audição/diagnóstico , Transtornos da Audição/epidemiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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.
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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.
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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.
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Envelhecimento , Vasos Retinianos , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Masculino , Envelhecimento/fisiologia , Retina , Arteríolas , EncéfaloRESUMO
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)â=â9; 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.
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Doença de Alzheimer , Humanos , Feminino , Masculino , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Biomarcadores , Inflamação , Estilo de Vida , Proteínas tauRESUMO
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.
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Auxiliares de Audição , Perda Auditiva , Humanos , Depressão/epidemiologia , Depressão/psicologia , Qualidade de Vida , Perda Auditiva/psicologia , CogniçãoRESUMO
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 (nâ=â24), 14 (nâ=â24), and 20 years (Nâ=â78) and plasma samples had been stored for 16 years (Nâ=â78). 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.
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Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Manejo de Espécimes , Temperatura , Idoso , Coleta de Amostras Sanguíneas , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/sangue , Fragmentos de Peptídeos , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
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.
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Transtornos Cognitivos , Disfunção Cognitiva , Idoso , Cognição , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Wisconsin/epidemiologiaRESUMO
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.
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Doença de Alzheimer , Doenças Neurodegenerativas , Feminino , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Biomarcadores , Proteínas de Neurofilamentos , Proteínas tau , Doenças Neurodegenerativas/patologia , Sensação , Pessoa de Meia-Idade , Destreza MotoraRESUMO
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.
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Disfunção Cognitiva , Transtornos do Olfato , Envelhecimento/psicologia , Cognição , Humanos , Pessoa de Meia-Idade , Acuidade VisualRESUMO
PURPOSE: To assess how health-related quality of life (HRQoL) varies by body mass index (BMI) category among gender and racial subgroups using nine HRQoL measures. METHODS: Among 3,710 US adults, we evaluated self-reported height, weight, and HRQoL that was measured by six indexes (EQ-5D; HUI2; HUI3; SF-6D; QWB-SA; HALex) and three summary measures (theta; PCS; MCS). Mean HRQoL was estimated by weighted regression for normal, overweight, and obese subgroups (BMI: 18.5-24.9 kg/m(2); 25-29.9; and 30-50). RESULTS: HRQoL was significantly lower (P < 0.0001) with increasing BMI category except for MCS. Obese individuals were 5.3 units lower on PCS (1-100 scale) and 0.05-0.11 lower on the HRQoL indexes (0-1 scale) than those with normal weight. MCS scores were significantly lower for obese than normal-weight among women (P = 0.04) but not men (P = 0.11). Overweight blacks had higher HRQoL than blacks in other BMI categories (P = 0.033). CONCLUSIONS: Six commonly used HRQoL indexes and two of three health status summary measures indicated lower HRQoL with obesity and overweight than with normal BMI, but the degree of decrement varied by index. The association appeared driven primarily by physical health, although mental health also played a role among women. Counter to hypotheses, blacks may have highest HRQoL when overweight.
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Obesidade/psicologia , Qualidade de Vida/psicologia , Grupos Raciais , Autorrelato , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Estatística como Assunto , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
Importance: Olfactory impairment is common in older adults. Identification of modifiable risk factors for olfactory impairment at midlife has the potential to reduce the burden of olfactory impairment at older ages. Objective: To determine the 10-year cumulative incidence of olfactory impairment and evaluate potentially modifiable risk factors for impairment including exposure to cadmium, lead, and tobacco smoke. Design, Setting, and Participants: Data from the Beaver Dam Offspring Study, a longitudinal cohort study of sensory health and aging in a general population, were available from examinations at baseline (2005-2008), 5 years (2010-2013), and 10 (2015-2017) years. A total of 2312 participants without olfactory impairment at baseline and with olfaction data available at the 5- and/or 10-year examination were included. The present study was conducted from April 28, 2020, to January 8, 2021. Main Outcomes and Measures: Olfactory impairment was measured by the San Diego Odor Identification Test. Cox discrete-time proportional hazards analyses were used to model associations between baseline covariates, including blood cadmium and lead levels and tobacco smoke exposure, and the 10-year cumulative incidence of olfactory impairment. Results: Of the 2312 participants, 1269 (54.9%) were women; mean age was 49 years (range, 22-84 years) at baseline. The 10-year cumulative incidence of olfactory impairment was 4.6% (95% CI, 3.7%-5.6%) and increased with age. Because of high collinearity, cadmium and tobacco smoke exposure were modeled separately. In a multivariable adjusted model, higher blood cadmium level (hazard ratio [HR], 1.70; 95% CI, 1.05-2.74) was associated with the 10-year cumulative incidence of olfactory impairment. Substituting tobacco smoke exposure for cadmium in the model, high exposure to tobacco smoke as a current smoker (HR, 2.94; 95% CI, 1.63-5.29, smoker vs no exposure) or from environmental tobacco smoke (HR, 2.65; 95% CI, 1.24-5.63, high vs no exposure) was also associated with an increased risk for developing olfactory impairment. Blood lead levels were not associated with olfactory impairment. Conclusions and Relevance: Results of this longitudinal cohort study suggest that modifiable environmental exposures may contribute to olfactory impairment that occurs with aging. Identification of modifiable risk factors for olfactory impairment may lead to prevention strategies that have the potential to reduce the burden of olfactory impairment at older ages.
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Cádmio/efeitos adversos , Exposição Ambiental , Chumbo/efeitos adversos , Transtornos do Olfato/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Wisconsin/epidemiologiaRESUMO
PURPOSE: To determine if incidence of contrast sensitivity (CS) impairment differs by generation and identify factors to explain these differences. METHODS: The Beaver Dam Eye Study (BDES) and Beaver Dam Offspring Study (BOSS) are cohort studies of aging adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 (BDES) and 2005-2008 (BOSS). Follow-up examinations occurred in five-year intervals. CS testing was conducted with Pelli-Robson letter sensitivity charts; Incident impairment was a log CS score <1.55 in either eye at follow-up. Associations of incidence with generation were investigated using estimated hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Participants (N = 3185) had a mean age of 51.9 years at baseline (standard deviation = 9.9) and 51.9% were female. Ten-year cumulative incidence of CS impairment was 40.1%, was higher among women (41.7%) than men (38.8%), and increased by age group. The risk of incident CS impairment decreased by 39% per generation. In multivariable models, the Baby Boom Generation (HR = 0.42, 95%CI = 0.31, 0.58) and Generation X (HR = 0.56, 95%CI = 0.34, 0.91) had a significantly decreased risk of CS impairment compared to the Greatest Generation. Results were similar in sensitivity analyses excluding those with cataract, age-related macular degeneration, or visual acuity impairment. CONCLUSION: The risk of incident CS impairment decreased by birth cohort, with the greatest reduction in the Baby Boom Generation. The difference in risk suggests that there are unknown modifiable risk factors that may help to further explain the etiology of CS impairment and provide potential pathways for prevention in the future.
Assuntos
Sensibilidades de Contraste , Transtornos da Visão , Envelhecimento , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Fatores de Risco , Acuidade Visual , Wisconsin/epidemiologiaRESUMO
Importance: Age-adjusted prevalence of hearing impairment (HI) decreased across generations in the 20th century, suggesting that HI is partially preventable. It is not known whether HI incidence differs by generation. Objectives: To examine whether HI incidence and change in pure-tone average (PTA) differ by generation and identify factors underlying these differences. Design, Setting, and Participants: This cohort study used data from the Epidemiology of Hearing Loss Study (EHLS) and Beaver Dam Offspring Study (BOSS), a pair of studies of adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 in the EHLS and 2005 to 2008 in BOSS, with two 5-year follow-up examinations in each cohort. This longitudinal cohort study assessed 3651 participants without HI at baseline who had follow-up data. Main Outcomes and Measures: The primary outcome was incident HI measured by pure-tone audiometry, defined as PTA greater than 25-dB hearing level (dB HL) in either ear. Associations of 5-year incidence were estimated by relative risks (RRs) and 10-year cumulative incidence with generation, as categorized by commonly used sociodemographic descriptors of year of birth, by hazard ratios (HRs). The 10-year change in PTA was investigated using a generation × time interaction term in generalized estimating equation models. Results: Among the 3651 participants (mean [SD] age at baseline 53.1 [10.6] years; 2255 [61.8%] female; and 3567 [97.7%] non-Hispanic White), the 5-year HI incidence was 14.1% (95% CI, 13.0%-15.3%) and the 10-year cumulative incidence was 26.0% (95% CI, 24.6%-27.6%). The incidence increased with age. The risk of 5-year incident HI decreased by generation (RR, 0.80; 95% CI, 0.66-0.97) when adjusting for multiple covariates. The decreased risk was similar in the 10-year period (HR, 0.86; 95% CI, 0.73-1.01). The PTA change rate (per 5 years of follow-up) decreased by generation, with the Greatest Generation (born 1901-1924) experiencing the highest rate (7.03 dB HL). The rates were all significantly lower for the other generations (Silent Generation [born 1925-1945], 3.30 dB HL; Baby Boom Generation [born 1946-1964], 3.36 dB HL; and Generation X [born 1965-1984], 2.33 dB HL). Conclusions and Relevance: This study suggests that the risk of HI and rate of PTA change is lower for the Silent Generation and Baby Boom Generation compared with the Greatest Generation. Part of this lower risk is likely associated with changes in modifiable factors. A potential continued benefit may exist for Generation X. Combined with the reduced risk of HI for the Silent Generation and Baby Boom Generation, this finding implies that the future HI burden may be lower than current estimates suggest.
Assuntos
Envelhecimento/fisiologia , Audiometria de Tons Puros , Perda Auditiva/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Wisconsin/epidemiologiaRESUMO
Purpose The dichotic digits test (DDT) is commonly administered in clinical and research settings, but it is not well understood how performance changes in aging. The purpose of this study is to determine the 5-year change on the free recall task and right ear advantage (REA) in a population-based cohort and factors associated with change. Method Participants in the population-based Epidemiology of Hearing Loss Study, who completed the DDT during the fourth (2009-2010) and fifth (2013-2016) examination periods were included (n = 865, M age = 72.8 years at baseline). Free recall DDT was administered using 25 sets of triple-digit pairs presented at 70 dB HL. The REA was calculated by subtracting the score in the left ear from the score in the right ear. Results In 5 years, most participants (62.4%) declined on free recall performance (mean decline = 3.0% [4.5 digits], p < .01). In age-sex-adjusted models, higher baseline scores, hearing impairment, and lower education were significantly associated with increased risk of decline. An REA at baseline (76.8%) and follow-up (77.9%) was common. Half of participants (50.6%) had a 5-year REA widening (M = 1.9% [1.4 digits], p = .01). Older age, but not hearing impairment, was associated with increased risk of REA widening. Conclusions The 5-year decline on free recall recognition performance was not associated with age but was associated with hearing impairment, whereas the 5-year widening of REA was associated with age but not hearing impairment. These results indicate that the REA may be a more sensitive measure of aging of the central auditory system than free recall performance.