Ronald Klein

Narrower retinal arteriolar caliber is linked to ~2-fold higher odds of LV concentric remodeling.

Narrower retinal arterioles linked to ~34% higher long-term CHD mortality.

1120: Patterns of Nat Recognition in Young Children: A Single-Center Report

KleinJournal of Exposure Science & Environmental Epidemiology

Evaluation and comparison of tools used to quantify aggregate PFAS exposure: Extractable organic fluorine, PFAS burden scores and summed PFAS concentrations

BACKGROUND: Bioaccumulation, widespread usage, and adverse human health effects emphasize per- and polyfluoroalkyl substances (PFAS) as an important public health concern. There is a need for an aggregate PFAS exposure measure due to the increasing diversity of structures. Aggregate measures are important for informing clinical care, biomonitoring, and research standardization. Current approaches for human biomonitoring of PFAS include targeting and quantifying a limited number of molecules and estimating exposure based on summed concentrations or statistical modeling. Extractable organofluorine (EOF) has been proposed as an aggregate PFAS biomarker that quantifies the total organically bound fluorine in a sample, encompassing PFAS regardless of knowing the exact chemical structures. However, EOF in human biomonitoring studies or environmental epidemiology is limited. OBJECTIVE: The objective of this study is to comprehensively assess human studies that measure EOF and target PFAS in the same sample by conducting a literature search, data extraction, and secondary data analysis. METHODS: We assessed the correlation of three aggregate PFAS exposure metrics with each other: EOF, adjusted summed concentrations of PFAS identified by the National Academies of Science Engineering and Medicine (NASEM), and PFAS burden scores. RESULTS: Across 8 published studies from US, Asia and Europe with 163 samples, EOF concentrations were higher than NASEM summed PFAS concentrations, and EOF was strongly associated with PFAS burden scores and NASEM sum. EOF does not identify or differentiate non-PFAS sources of fluorine which limits identification of individual molecules and their potential toxicity. SIGNIFICANCE: Correlations between EOF, summed targeted PFAS concentrations, and PFAS burden scores demonstrated that EOF is a practical tool for estimating PFAS exposure and identifying individuals with high exposure to PFAS. Thus, EOF could be utilized for identifying individuals or sub-populations with high aggregate PFAS exposure. Practical considerations in laboratory analyses, including instrumentation, sample matrix, and sample extraction procedure, remain potential barriers to widespread implementation of EOF as a biomonitoring tool. IMPACT: This study highlights the potential of extractable organofluorine (EOF) as a comprehensive biomarker for assessing aggregate PFAS exposure in human populations. By analyzing data from eight studies across the US, Asia, and Europe, we found that EOF concentrations were higher than summed PFAS concentrations and correlated strongly with PFAS burden scores. Although EOF does not identify specific fluorine sources, its strong associations suggest it is a practical tool for detecting high PFAS exposure. While EOF offers promise for identifying at-risk populations, practical challenges in laboratory analyses may limit its widespread use in biomonitoring programs.

Genome-Wide Association Study of Quantitative Kidney Function in 52,531 Individuals with Diabetes Identifies Five Diabetes-Specific Loci

Key Points Comprehensive genome-wide association study of eGFR in diabetes, accounting for diabetes duration, kidney disease, and known modifiers, identified novel genetic effects. Incorporation of various kidney multi-omics data provides supporting evidence for the role of novel genome-wide association study loci in diabetic kidney disease. Background Diabetic kidney disease (DKD) is a serious diabetes complication caused by both environmental and genetic risk factors. Previous genome-wide association studies (GWAS) have identified several loci associated with kidney function and kidney disease in the general population and, to a lesser extent, in diabetes. Methods To uncover the genetic factors driving diabetes-induced kidney function, we conducted a series of GWAS meta-analyses of eGFR in 17,267 individuals with type 1 diabetes and 35,264 with type 2 diabetes (52,531 total), using multiple well-characterized cohorts of type 1 diabetes DKD and data from the UK Biobank and SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools (SUMMIT) consortium. We further accounted for DKD case/control status, diabetes duration and subtype, body mass index, glycated hemoglobin levels, and the relationship between eGFR and albuminuria. Results GWAS identified 13 loci associated with eGFR ( P < 5×10 −8 ), with five loci (candidate genes: HIPK3 , TRIM5 , RORA , ERBB4 , and BCL6 / LPP ) not associated with or were in opposite directions as compared with eGFR in the general population. Four candidate genes ( HIPK3 , BCL6, LPP , and RORA ) demonstrated evidence of differential expression in kidney compartments and cells among subgroups with DKD or diabetes versus controls. Lead single-nucleotide polymorphisms rs8027829 ( RORA ) and rs76300256 ( BCL6/LPP ) were methylation quantitative trait loci in whole blood and kidney tissue, respectively, and rs76300256 and its related CpGs all cluster in a kidney enhancer. Conclusions Our integrated approach identified candidate genes with diabetes-specific effects on kidney function.

Quantitative insights into the efficacy of genome-resolved surveys of microbial communities through ribosomal protein phylogeography and EcoPhylo

The increasing availability of microbial genomes is essential to gain insights into microbial ecology and evolution that can propel biotechnological and biomedical advances. Recent advances in genome recovery have significantly expanded the catalogue of microbial genomes from diverse habitats. However, the ability to explain how well a set of genomes account for the diversity in a given environment remains challenging for individual studies or biome-specific databases. Here we present EcoPhylo, a computational workflow to characterize the phylogeography of any gene family through integrated analyses of genomes and metagenomes, and apply this approach to ribosomal proteins to quantify phylogeny-aware genome recovery rates in two genome-resolved investigations of the human gut and oral cavity. Our results demonstrate that EcoPhylo reveals highly resolved, reference-free, multi-domain phylogenies in conjunction with distribution patterns of individual clades across environments, providing a means to assess genome recovery in individual studies and benchmark genome collections.

Brachial Plexus Anatomy of Sprague Dawley Rat Compared to Human

Brachial plexus injury (BPI) occurs when the brachial plexus (BP) is compressed, stretched, or avulsed. A mild BPI results in acute arm pain, tingling, or numbness, while more severe injuries can lead to permanent muscle weakness or loss of function of the extremity if left untreated. Many BPI treatments developed in small animal models fail to translate effectively to human clinical trials. Furthermore, there is a lack of comparative studies exploring the anatomical differences between BPs in different species. The objective of this study is to compare the BP anatomy between humans and Sprague–Dawley (SD) rats to determine if the SD rat is a suitable model for studying BPI mechanisms and treatments. Four human BPs were compared to five SD rat BPs. Gross anatomical analysis revealed mild similarities in the branching patterns of SD rat and human BP. Histological results indicated that SD rats had significantly smaller musculocutaneous (p = 0.0095), median (p < 0.0001), and ulnar (p < 0.0001) nerves compared to humans. Additionally, SD rats had significantly fewer axons than humans in the musculocutaneous (p = 0.0190), median (p < 0.0001), and ulnar nerves (p < 0.0001). Due to the anatomical and histological differences between the two species, therapeutic interventions for BPIs developed in rats should be further tested in a larger animal model, such as the Wisconsin Miniature Swine, before progressing to human clinical trials.

Treatment of subclinical hyperthyroidism in patients older than 50 years: a randomized controlled study

Objective Subclinical hyperthyroidism (SCH) is common and associated with atrial fibrillation (AF) risk in the elderly. Current guidelines rely on a low level of evidence. Methods Randomized clinical trial including patients 50 years and older, with thyroid-stimulating hormone (TSH) <0.4 mU/L and normal thyroid hormone concentrations. All patients showed autonomy on thyroid scan. They were randomized either to receive radioiodine (I-131) or to be monitored and treated only if they underwent AF or evolved toward overt hyperthyroidism. Primary outcome was the onset of new AF. Secondary outcomes were treatment-induced hypothyroidism rate and health-related quality of life. Results One hundred forty-four patients (mean age: 65.3 ± 8.9 years, 76% females) were randomized, 74 to surveillance and 70 to treatment. Four patients in the surveillance group and one in the treatment group developed AF ( P = 0.238). However, the patient who developed AF in the treatment group maintained TSH <0.4 mU/L at AF onset. A post-hoc analysis was carried out and showed that when normalization of TSH was considered, the risk of AF was significantly reduced ( P = 0.0003). In the surveillance group, several patients showed no classical characteristics associated with AF risk, including age >65 years or TSH < 0.1mU/L. Of 94 patients treated using radioiodine, 25% developed hypothyroidism during follow-up. Conclusion Due to recruitment difficulties, this study failed to demonstrate that SCH treatment can significantly reduce the incidence of AF in patients older than 50 years with thyroid autonomy even if all the patients who developed AF maintained TSH <0.4 mU/L. This result must be balanced with the increased risk of radioiodine-induced hypothyroidism.

Coauthoring with Undergraduate Students

his article focuses on the coauthoring experience of fifteen undergraduate college students and their English professor to write this article. We focus on figured world theory to explain the power dynamics we have encountered through our research about undergraduate coauthoring and how those power dynamics have come into play in writing this article. We also discuss what has worked well for us and what challenges we have faced.

Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi‐Ethnic Study of Atherosclerosis (MESA)

Association of macular pigment optical density with retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma

We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG.

Prevalence, Progression, and Modifiable Risk Factors for Diabetic Retinopathy in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study

Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes.

Association of Dietary Nitrate and a Mediterranean Diet With Age-Related Macular Degeneration Among US Adults

Importance: Low dietary nitrate intake has previously been suggested to be a risk factor for age-related macular degeneration (AMD) progression; however, this finding has not been replicated in other cohorts or adjusted for dietary patterns. Objective: To determine whether there is an association between dietary nitrate intake and AMD progression. Design, Setting, and Participants: This cohort study analyzed data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and their extended follow-up studies, which were conducted in multicenter outpatient retinal practices. Participants in both trials had non-late AMD in at least 1 eye. Data were analyzed from March 1, 2020, to September 30, 2022. Exposure: Dietary nitrate intake. Main Outcomes and Measures: Association between dietary nitrate intake and development of late AMD (neovascular AMD [nAMD] or geographic atrophy [GA]) or large drusen. The interactions of dietary patterns, with common at-risk single-nucleotide polymorphisms, were also assessed. Results: In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants [110 of whom participated in both studies]), there were 13 511 eligible eyes. The combined cohort comprised 4396 women (56%) and 3392 men (44%), and the combined mean (SD) age was 71.1 (6.6) years. Dietary nitrate intake was associated with a decreased risk of progression to late AMD in the combined AREDS/AREDS2 cohort (hazard ratio [HR], 0.77 [95% CI, 0.69-0.86] for quartile 4 vs quartile 1 of intake) and a decreased risk of GA (HR, 0.71 [95% CI, 0.61-0.83]) and nAMD (HR, 0.85 [95% CI, 0.73-0.99]). In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD (HR, 0.77 [95% CI, 0.65-0.91]) and GA (HR, 0.80 [95% CI, 0.65-0.97]) but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD (HR, 0.90 [95% CI, 0.80-1.02]) or nAMD (HR, 0.93 [95% CI, 0.78-1.11]). There was a correlation between Mediterranean dietary patterns and dietary nitrate intake (r = 0.52, P < .001). Conclusions and Relevance: The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. These results are subject to potential bias and are hypothesis-generating in nature; therefore, they are insufficient to support new clinical recommendations. Previously described associations between dietary nitrate intake and AMD may in fact represent overall dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.

Association between cognitive function and large optic nerve cupping, accounting for cup-disc-ratio genetic risk score

PURPOSE: To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. DESIGN: This was a retrospective study using data from the Women's Health Initiative. METHODS: Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. RESULTS: Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). CONCLUSIONS: Independent of the CDR GRS, women with large CDR had a lower cognitive function.

ChewJAMA Ophthalmology

Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression

Importance: After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. Objective: To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). Design, Setting, and Participants: This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. Interventions: During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Main Outcomes and Measures: Self-reported lung cancer and late AMD validated with medical records. Results: This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Conclusions and Relevance: Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

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.

Larger baseline CRVE is linked to ~10% higher risk of incident depressive symptoms per SD.

Association between Cognitive Function and Large Optic Nerve Cupping, Accounting for Cup-Disc-Ratio Genetic Risk Score

Purpose To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. Design This was a retrospective study using data from the Women’s Health Initiative. Methods Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. Results Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). Conclusions Independent of the CDR GRS, women with large CDR had a lower cognitive function.

Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes

Significance Statement Genetic differences are possible contributing factors to the substantial unexplained variability in rates of renal function loss in type 1 diabetes. Gene-based testing of protein coding genetic variants in whole-exome scans of individuals with type 1 diabetes with advanced kidney disease, as opposed to genome-wide SNP analyses, revealed that carriers of rarer, disruptive alleles in HSD17B14 experienced net protection against loss of kidney function and development of ESKD. HSD17B14 encodes hydroxysteroid 17- β dehydrogenase 14, which regulates sex steroid hormone metabolism. Paradoxically, proximal tubules from patients and mouse models had high levels of expression of the gene and protein, with downregulation in the presence of kidney injury. Hydroxysteroid 17- β dehydrogenase 14 may therefore be a druggable therapeutic target. Background Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of ESKD in individuals with type 1 diabetes at advanced kidney disease stage. Methods Gene-based exome array analyses of 15,449 genes in five large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time to ESKD, testing the top gene in a sixth cohort ( n =2372/1115 events all cohorts) and replicating in two retrospective case-control studies ( n =1072 cases, 752 controls). Deep resequencing of the top associated gene in five cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models. Results Protein coding variants in the hydroxysteroid 17- β dehydrogenase 14 gene ( HSD17B14 ), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance ( n =4196; P value=3.3 × 10 −7 ). The HSD17B14 gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed HSD17B14 gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other CKD-associated renal pathologies. Conclusions HSD17B14 gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.

Benefit of Musical Training for Speech Perception and Cognition Later in Life

Purpose The aim of this study was to determine the long-term associations of musical training with speech perception in adverse conditions and cognition in a longitudinal cohort study of middle-age to older adults. Method This study is based on Epidemiology of Hearing Loss Study participants. We asked participants at baseline (1993-1995) about their musical training. Speech perception (word recognition in competing message; Northwestern University Auditory Test Number 6), cognitive function (cognitive test battery), and impairment (self-report or surrogate report of Alzheimer's disease or dementia, and/or a Mini-Mental State Examination score ≤ 24) were assessed up to 5 times over the 20-year follow-up. We included 2,938 Epidemiology of Hearing Loss Study participants who had musical training data and at least one follow-up of speech perception and/or cognitive assessment. We used linear mixed-effects models to determine associations between musicianship and decline in speech perception and cognitive function over time and Cox regression models to evaluate associations of musical training with 20-year cumulative incidence of speech perception and cognitive impairment. Models were adjusted for age, sex, and occupation and repeated with additional adjustment for health-related confounders and education. Results Musicians showed less speech perception decline over time with stronger effects in women (0.16% difference, 95% confidence interval [CI] [0.05, 0.26]). Among men, musicians had, on average, better speech perception than nonmusicians (3.41% difference, 95% CI [0.62, 6.20]) and were less likely to develop a cognitive impairment than nonmusicians (hazard ratio = 0.58, 95% CI [0.37, 0.91]). Conclusions Musicians showed an advantage in speech perception abilities and cognition later in life and less decline over time with different magnitudes of effect sizes in men and women. Associations remained with further adjustment, indicating that some degree of the advantage of musical training is independent of socioeconomic or health differences. If confirmed, these findings could have implications for developing speech perception intervention and prevention strategies. Supplemental Material https://doi.org/10.23641/asha.14825454.