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We examined the associations between lung function and incident dementia and cognitive decline in 12,688 participants in the ARIC Study who provided lung function measurements in 1990-1992. Cognitive tests were administered up to 7 times, and dementia was ascertained through 2019. We used shared parameter models to jointly fit proportional hazard models and linear mixed-effect models to estimate lung-function-associated dementia rate and cognitive change, respectively. Higher forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were associated with reduced dementia (n = 2,452 persons developed dementia); hazard ratios per 1-L increase in FEV1 and FVC were 0.79 (95% confidence interval (CI): 0.71, 0.89) and 0.81 (95% CI: 0.74, 0.89), respectively. Each 1-L increase in FEV1 and FVC was associated with a 0.08-standard deviation (SD) (95% CI: 0.05, 0.12) and a 0.05-SD (95% CI: 0.02, 0.07) attenuation of 30-year cognitive decline, respectively. A 1% increase in FEV1/FVC ratio was associated with 0.008-SD (95% CI: 0.004, 0.012) less cognitive decline. We observed statistical interaction between FEV1 and FVC, suggesting that cognitive declines depended on values of specific FEV1 and FVC (as compared with FEV1, FVC, or FEV1/FVC ratio models that suggested linear incremental associations). Our findings may have important implications for reducing the burden of cognitive decline that is attributable to environmental exposures and associated lung function impairment.
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Aterosclerose , Disfunção Cognitiva , Demência , Humanos , Pulmão , Volume Expiratório Forçado , Aterosclerose/epidemiologia , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Demência/etiologiaRESUMO
BACKGROUND: Dream-enacting behavior is a characteristic feature of rapid eye movement sleep behavior disorder, the most specific prodromal marker of synucleinopathies. Pesticide exposure may be associated with dream-enacting behaviors, but epidemiological evidence is limited. OBJECTIVES: To examine high pesticide exposure events in relation to dream-enacting behaviors among farmers in the Agricultural Health Study. METHODS: We conducted multivariable logistic regression analyses to examine high pesticide exposure events reported from 1993 to 1997 in relation to dream-enacting behaviors assessed from 2013 to 2015 among 11,248 farmers (age 47 ± 11 years). RESULTS: A history of dream-enacting behaviors was reported by 939 (8.3%) farmers. Compared with farmers who did not report any high pesticide exposure event, those who reported were more likely to endorse dream-enacting behaviors 2 decades later (odds ratio = 1.75; 95% confidence interval [CI], 1.49-2.05). The association appeared stronger when there was a long delay in washing with soap and water after the event (2.63 [95% CI, 1.62-4.27] for waiting >6 hours vs. 1.71 [95% CI, 1.36-2.15] for washing within 30 minutes) and when the exposure involved the respiratory or digestive tract (2.04 [95% CI, 1.62-2.57] vs. 1.58 [95% CI, 1.29-1.93] for dermal contact only). In the analyses of specific pesticides involved, we found positive associations with two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), four organophosphate insecticides (phorate, ethoprop, terbufos, and parathion), two herbicides (alachlor and paraquat), and fungicides as a group. CONCLUSIONS: This study provides the first epidemiological evidence that high pesticide exposures may be associated with a higher risk of dream-enacting behaviors. © 2022 International Parkinson and Movement Disorder Society.
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Inseticidas , Exposição Ocupacional , Praguicidas , Adulto , Agricultura , Fazendeiros , Humanos , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversosRESUMO
OBJECTIVES: Pyrethroid insecticides have been linked with multiple health outcomes. One study reported an association with increased all-cause and cardiovascular mortality. Given the widespread use of pyrethroids, these findings warrant confirmation. We explored associations of permethrin/pyrethroid use with overall and cause-specific mortality among 50 665 licensed pesticide applicators in the Agricultural Health Study. METHODS: At enrolment (1993-1997), participants self-reported information on permethrin/pyrethroid use. Information on causes of death came from linkage with death registries through 2016. We used Cox proportional hazards models to estimate HRs and 95% CIs with adjustment for potential confounders. RESULTS: Over an average 21 years of follow-up, 19.6% (9,955) of the cohort died. We found no clear evidence that ever-use of permethrin/pyrethroid was associated with elevated overall mortality or with mortality from most causes examined. There was suggestive evidence, based on a small number of deaths among those exposed, for elevated pyrethroid-associated mortality from some neurological, respiratory and genitourinary diseases in the overall sample and from lung cancer among never-smokers. CONCLUSION: Although based on mortality, which is also affected by survival, rather than incidence, these findings are biologically plausible, and future investigations in other populations may be warranted.
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Inseticidas , Exposição Ocupacional , Praguicidas , Piretrinas , Agricultura , Humanos , Inseticidas/efeitos adversos , Exposição Ocupacional/efeitos adversos , Permetrina/efeitos adversos , Piretrinas/efeitos adversosRESUMO
BACKGROUND: Pesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction. OBJECTIVE: We evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study. METHODS: Serum creatinine was measured in 1545 BEEA participants and estimated glomerular filtration rate (eGFR) was calculated with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Using reported information on lifetime use of 41 pesticides, multivariable linear and logistic regression was used to examine associations with eGFR modeled continuously and with CKD (eGFR <60 mL/min/1.73 m2), respectively. Models were adjusted for possible confounding factors related to kidney function and correlated pesticides. RESULTS: Lower eGFR was observed among pesticide applicators who ever used the herbicides pendimethalin (-3.7%, 95% confidence interval (CI): 5.8%, -1.5%), atrazine (-3.7%, 95% CI: 6.9%, -0.4%), and dicamba (-2.8%, 95% CI: 5.3%, -0.2%) compared with never users of each pesticide. Ever use of pendimethalin (odds ratio (OR)=1.6, 95% CI: 1.1, 2.2) and atrazine (OR=1.8, 95% CI: 1.0, 3.0) was also associated with elevated odds of CKD, with an exposure-response association between intensity-weighted lifetime days of pendimethalin use and CKD among active farmers (N=1302; ptrend=0.04). Atrazine use within the last year was associated with lower eGFR and elevated odds of CKD when compared with never users, and we observed exposure-response associations with intensity-weighted lifetime days among recent users. Use of several other pesticides was associated with higher eGFR. DISCUSSION: These results suggest that two widely used herbicides, pendimethalin and atrazine, may be associated with altered kidney function among pesticide applicators. Our findings for these herbicides are consistent with observed associations with end-stage renal disease in the Agricultural Health Study.
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Exposição Ocupacional , Praguicidas , Agricultura , Biomarcadores , Fazendeiros , Humanos , Rim , Masculino , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidadeRESUMO
OBJECTIVES: Pesticide exposure may impair human olfaction, but empirical evidence is limited. We examined associations between occupational use of 50 specific pesticides and olfactory impairment, both self-reported, among 20 409 participants in the Agricultural Health Study, a prospective cohort of pesticide applicators (mostly farmers, 97% male). METHODS: We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between pesticide use at enrolment (1993-1997) and olfactory impairment reported two decades later (2013-2016), adjusting for baseline covariates. RESULTS: About 10% of participants reported olfactory impairment. The overall cumulative days of any pesticide use at enrolment were associated with a higher odds of reporting olfactory impairment (OR (highest vs lowest quartile): 1.17 (95% CI: 1.02 to 1.34), p-trend = 0.003). In the analyses of 50 specific pesticides, ever-use of 20 pesticides showed modest associations with olfactory impairment, with ORs ranging from 1.11 to 1.33. Of these, higher lifetime days of use of 12 pesticides were associated with higher odds of olfactory impairment compared with never use (p-trend ≤ 0.05), including two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), two organophosphate insecticides (diazinon and malathion), permethrin, the fungicide captan and six herbicides (glyphosate, petroleum distillates, 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid and metribuzin), although many of these did not exhibit clear, monotonic exposure-response patterns. CONCLUSION: Overall, we found relatively broad associations between pesticides and olfactory impairment, involving many individual pesticides and covering several chemical classes, suggesting that pesticides could affect olfaction through multiple pathways. Future epidemiological studies with objective measurement of olfaction are required to confirm these findings.
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BACKGROUND: Extensive literature suggests an association between general pesticide use and Parkinson's disease (PD). However, with few exceptions, little is known about associations between specific pesticides and PD. OBJECTIVE: We evaluated use of pesticides and incident PD in 38,274 pesticide applicators and 27,836 of their spouses in the Agricultural Health Study cohort followed over 20 years. METHODS: We used self-reported information on ever-use of 50 specific pesticides as of enrollment for both applicators and spouses, and considered intensity-weighted lifetime days (IWLD) reported at enrollment and through the first 5-year follow-up among applicators. We estimated covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. We also examined heterogeneity in associations by history of head injury and chemical resistant glove use. RESULTS: A total of 373 applicators and 118 spouses self-reported incident doctor-diagnosed PD. Ever-use of the insecticide terbufos (HR:1.31, 95%CI:1.02-1.68) and the herbicides trifluralin (HR:1.29, 95%CI: 0.99-1.70) and 2,4,5-T (HR:1.57, 95%CI:1.21-2.04) was associated with elevated PD risk. On the other hand, diazinon (HR:0.73, 95%CI: 0.58-0.94) and 2,4,5-TP (HR:0.39, 95%CI:0.25-0.62) were associated with reduced risk. We observed heterogeneity in ever-use associations by head injury and chemical-resistant glove use for some pesticides, with higher risk among those who reported a history of head injury, or who did not use gloves. PD risk was also elevated for applicators in the highest category of IWLD for dichlorvos, permethrin (animal use), and benomyl. CONCLUSIONS: We found evidence of increased PD risk for some pesticides. Our results also suggest higher susceptibility for pesticide-associated PD among individuals with head injury as well as protection with use of chemical resistant gloves, although further research is needed to understand the impact of head injury. Research on current and newer pesticides, including mechanisms relevant to PD, is important given widespread pesticide use.
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Exposição Ocupacional , Doença de Parkinson , Praguicidas , Agricultura , Estudos de Coortes , Fazendeiros , Humanos , Iowa , North Carolina , Exposição Ocupacional/efeitos adversos , Doença de Parkinson/epidemiologia , Doença de Parkinson/etiologia , Praguicidas/toxicidade , CônjugesRESUMO
PURPOSE: To evaluate cancer incidence in the Agricultural Health Study (AHS), a cohort of private pesticide applicators, their spouses, and commercial applicators, based on 12,420 cancers, adding 5,989 cancers, and 9 years of follow-up since last evaluation. METHODS: We calculated age, year, sex, and race-adjusted standardized incidence ratios (SIR) and 95% confidence intervals (CI) for cancer sites in the AHS relative to the general population. RESULTS: Overall AHS cancer incidence was lower than the general population (SIRprivate = 0.91, CI 0.89-0.93; SIRspouse = 0.89, CI 0.86-0.92; SIRcommercial = 0.83, CI 0.76-0.92), with notable deficits across applicators and spouses for oral cavity, pancreas, and lung cancers. Cancer excesses included prostate cancer, lip cancer, certain B-cell lymphomas (e.g., multiple myeloma), acute myeloid leukemia (AML), thyroid cancer, testicular cancer, and peritoneal cancer. The lung cancer deficit was strongest among applicators reporting potential exposure to endotoxin at study enrollment (tasks such as raising animals and handling stored grain). CONCLUSIONS: Although an overall deficit in cancer was observed, there were notable exceptions, including newly observed excesses for AML, thyroid, testicular, and peritoneal cancers. Furthermore, endotoxin exposure may, in part, account for observed lung cancer incidence deficits. Cancer incidence patterns in the AHS suggest farm exposures' relevance to cancer etiology.
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Neoplasias/epidemiologia , Exposição Ocupacional/efeitos adversos , Praguicidas , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cônjuges/estatística & dados numéricosRESUMO
OBJECTIVES: Lower mortality rates compared with the general population have been reported for Agricultural Health Study (AHS) participants (enrolled 1993-1997) followed through 2007. We extended analysis of mortality among AHS participants (51 502 private pesticide applicators, their 31 867 spouses and 4677 commercial pesticide applicators from North Carolina and Iowa) through 2015 and compared results using several analytical approaches. METHODS: We calculated standardised mortality ratios (SMRs), causal mortality ratios (CMR) and relative SMRs (rSMR) using state-specific mortality rates of the general populations as the referent. RESULTS: Over the average 16 years of follow-up (1999-2015), 9305 private applicators, 3384 spouses and 415 commercial applicators died. SMRs and CMRs, with expected deaths calculated using the person-time among the cohort and the general population, respectively, indicated lower overall mortality in all study subgroups (SMRs from 0.61 to 0.69 and CMRs from 0.74 to 0.89), although CMRs indicated elevated mortality in private applicators from North Carolina and in ever-smokers. In SMR analyses, there were fewer than expected deaths from many causes, but deaths from some external causes including transportation-related injuries and mechanical forces were elevated in private applicators. CMRs indicated higher than expected deaths from prostate cancer, lymphohaematopoietic cancers, Parkinson's and Alzheimer's disease, and chronic glomerulonephritis in private applicators, and non-Hodgkin's lymphoma in spouses (from 1.19 to 1.53). rSMR results were generally elevated, similar to CMR findings. CONCLUSIONS: AHS participants experienced lower overall mortality than the general population.Mortality from a few specific causes was increased in private applicators, specifically when CMR and rSMR approaches were used.
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Doenças dos Trabalhadores Agrícolas/mortalidade , Mortalidade , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Praguicidas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fazendeiros , Feminino , Humanos , Iowa/epidemiologia , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Cônjuges , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
BACKGROUND: Few studies have evaluated associations between pesticides and hyperthyroidism. OBJECTIVE: We evaluated associations between specific pesticides and incident hyperthyroidism in private pesticide applicators in the Agricultural Health Study. METHODS: We used Cox proportional hazards models to estimate HRs and 95% CIs for associations between pesticide use at enrolment and hyperthyroidism (n=271) in 35 150 applicators (mostly men), adjusting for potential confounders. RESULTS: Ever use of several pesticides (organophosphate insecticide malathion, fungicide maneb/mancozeb, herbicides dicamba, metolachlor, and atrazine in overall sample and chlorimuron ethyl among those ≤62 years) was associated with reduced hyperthyroidism risk, with HRs ranging from 0.50 (95% CI 0.30 to 0.83) for maneb/mancozeb to 0.77 (95% CI 0.59 to 1.00) for atrazine. Hyperthyroidism risk was lowest among those with higher intensity-weighted lifetime days of using carbofuran and chlorpyrifos (ptrend ≤0.05). CONCLUSIONS: Observed associations between pesticides and decreased risk of hyperthyroidism warrant further investigation.
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Hipertireoidismo/etiologia , Praguicidas/efeitos adversos , Adulto , Idoso , Agricultura/instrumentação , Agricultura/métodos , Humanos , Hipertireoidismo/epidemiologia , Hipertireoidismo/metabolismo , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/metabolismo , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
PURPOSE: Perfluoroalkyl substances (PFASs) are environmentally persistent amphiphilic compounds. Exposure to two PFASs, perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) is linked to specific occupations and industries. This study examines the contribution of past occupational PFAS exposure to serum PFOS and PFOA levels among 154 older adults in New York State. METHODS: Serum PFOS and PFOA levels were compared to data from the National Health and Nutrition Examination Survey (NHANES). Potential occupational exposure to any PFAS was determined from work histories, reviewed by an industrial hygienist, and assessed in relation to current serum PFOS and PFOA levels using exposure probability, duration and cumulative exposure. RESULTS: We observed 25% higher serum PFOS and 80% higher PFOA levels in study participants compared to NHANES. No participants reported PFAS chemical manufacturing work, but n = 68 reported work in occupations and industries known to use PFASs. We found that participants with high cumulative workplace exposure had 34% higher serum PFOS levels compared to participants without occupational exposure, adjusted for age, sex and income. Serum PFOS levels were 26% higher for participants with longer occupational exposure durations. The probability of occupational PFAS exposure metric was not associated with serum PFOS. Serum PFOA was not associated with any measure of occupational exposure. CONCLUSION: Occupational exposure may contribute to total PFOS body burden in this study population, even among workers not directly involved in manufacturing PFASs. PFAS exposure assessments should evaluate the workplace as a potential source, even when workplace exposures are assumed to be low or moderate.
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Ácidos Alcanossulfônicos/sangue , Caprilatos/sangue , Exposição Ambiental/análise , Fluorocarbonos/sangue , Inquéritos Nutricionais/estatística & dados numéricos , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York , Exposição Ocupacional/análise , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos , Fatores de TempoRESUMO
BACKGROUND: Low vitamin D levels are common among patients with Parkinson's disease (PD). Experimental evidence further suggests that vitamin D may be protective against PD. The objective of this study was to prospectively assess the association between serum 25-hydroxyvitamin D and PD among 12,762 participants of the Atherosclerosis Risk in Communities Study cohort. METHODS: Serum samples were collected in 1990-1992, and 25-hydroxyvitamin D was measured by liquid chromatography mass spectrometry. A total of 67 incident PD cases were identified through December 31, 2008. The median length of follow-up was 17 years. We used Cox proportional hazards models to obtain hazard ratios and 95% confidence intervals, adjusting for age, sex, and race. We did not find any association between serum 25-hydroxyvitamin D concentrations and PD risk, regardless of how serum 25-hydroxyvitamin D was modeled. Compared with participants with serum 25-hydroxyvitamin D < 20 ng/mL, the hazards ratio for PD was 1.05 (95% confidence interval, 0.58-1.90) for 20-30 ng/mL and 1.14 (95% confidence interval, 0.59- 2.23) for ≥30 ng/mL. Similar results were obtained in sensitivity analyses that included white participants only and that were stratified by the length of follow-up. CONCLUSION: This prospective study lends no support to the hypothesis that vitamin D may reduce the risk of PD. © 2016 International Parkinson and Movement Disorder Society.
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Doença de Parkinson/sangue , Vitamina D/análogos & derivados , Assistência ao Convalescente , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Vitamina D/sangueRESUMO
Study Objectives: Retinal microvascular pathology (RMP) and obstructive sleep apnea (OSA) are both cardiovascular disease risk factors. Limited data exists on their interrelationship. We tested the hypotheses that OSA and nocturnal hypoxemia would be associated with RMP and vessel calibers. Methods: We conducted a quasi-cross-sectional analysis of 1625 participants in the Atherosclerosis Risk in Communities Sleep Heart Health Study. Participants completed in-home polysomnography monitoring (1996-1998) and were categorized by OSA severity (apnea-hypopnea index: <5, 5-14.9, and ≥15) and proportion of total sleep time with oxygen saturationâ <â 90% (T90). Retinal photography (1993-1995) was used to assess RMP and measure vascular diameters (central retinal arteriolar equivalent [CRAE] and central retinal venular equivalent [CRVE]). Logistic and linear models were adjusted for demographics, behaviors, and BMI. Results: Of the participants, 19% had OSA (AHIâ >â 15) and 4% had RMP. Severe OSA was not associated with RMP [OR (95% CI): 1.08 (0.49 to 2.38)] or CRAE in adjusted models. OSA severity showed a positive linear relationship with CRVE; adjusted mean CRVE for those with OSA was 195.8 µm compared to 193.2 µm for those without OSA (Ptrendâ =â 0.03). T90 was strongly associated with CRVE, but not with RMP or CRAE. Adjusted mean CRVE for T90â ≥â 5% was 199.0 and 192.9 for T90â <â 1% (ptrendâ <â 0.0001). Conclusions: OSA and T90 were not associated with RMP or CRAE. However, both OSA and T90â ≥â 5% were associated with wider venules, which may be early and indicative changes of increased inflammation and future risk of stroke and CHD.
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Background: Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke. Objective: We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations. Methods: Lung function was measured at participants' midlife in 1990-1992 (mean ageâ=â56±5 years) and later-life in 2011-2013 (mean ageâ=â76±5 years), and brain MRI was performed in 2011-2013. Linear regression models were used to examine the associations of lung function with brain and white matter hyperintensity (WMH) volumes, and logistic regression models were used for cerebral infarcts and microbleeds, adjusting for potential confounders. Results: In cross-sectional analysis (i.e., examining later-life lung function and MRI markers, nâ=â1,223), higher forced-expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with larger brain and lower WMH volumes [e.g., 8.62 (95% CI:2.54-14.71) cm3 greater total brain volume per one-liter higher FEV1]. No association was seen with microbleeds in the overall sample, but higher FVC was associated with lower odds of microbleeds in never-smokers and higher odds in ever-smokers. In the cross-temporal analysis (i.e., associations with midlife lung function, nâ=â1,787), higher FVC levels were significantly associated with lower later-life brain volumes. Conclusions: Our results support modest associations of better lung function with less neurodegenerative and cerebrovascular pathology, although findings for microbleeds were unexpected in ever-smokers.
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Encéfalo , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Aterosclerose/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Pulmão/patologia , Testes de Função Respiratória , Capacidade Vital , Idoso de 80 Anos ou maisRESUMO
IMPORTANCE: Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. OBJECTIVE: To identify the genetic loci associated with olfactory dysfunction in the general population. DESIGN SETTING AND PARTIICIPANTS: This genome-wide association study meta-analysis (GWMA) included participants of European ancestry (N = 22,730) enrolled in four different large population-based studies, followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). The data analysis was performed from March 2023 through June 2024. EXPOSURES: Genome-wide single nucleotide polymorphisms. MAIN OUTCOMES AND MEASURES: Olfactory dysfunction was the outcome and assessed using a 12-item smell identification test. RESULTS: GWMA revealed a novel genome-wide significant locus (tagged by rs11228623 at 11q12) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes. CONCLUSIONS: These findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health. Question: What is the genetic basis of olfactory dysfunction, and is it causally related to adverse health outcomes? Findings: This genome-wide association study meta-analysis (GWMA) of 22,730 European and 1,030 African participants identified a novel genomic locus, enriched for olfactory receptor genes, robustly associated with olfactory dysfunction. Two-sample Mendelian Randomization analyses provided evidence for causal associations of olfactory dysfunction with biochemical, anthropometric and cardiovascular health outcomes. Meaning: These findings provide new insights into the genetic architecture of olfaction and implicate olfactory dysfunction as a causal risk factor for many aspects of human health.
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At visit 3 (1993-1995) of the ARIC Study, 1.5T brain MRI was completed in 1,881 stroke-free participants (Mean ageâ=â62.9±4.9, 50% Black). Cox regression examined associations between infarct group [infarct-free (referent; nâ=â1,611), smaller only (<3âmm; nâ=â50), larger only (≥3âmm but <20âmm; nâ=â185), both (nâ=â35)] and up to 25-year incident dementia (nâ=â539). Participants with both infarcts were over 2.5 times more likely to develop dementia [HRâ=â2.61; 95% CIâ=â1.44, 4.72]. Smaller only (HRâ=â1.22; 95% CIâ=â0.70, 2.13) and larger only (HRâ=â1.27; 95% CIâ=â0.92, 1.74) groups showed associations with wide confidence intervals, unsupported statistically. A late midlife infarct profile including smaller and larger infarcts may represent particular vulnerability to dementia risk.
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Aterosclerose , Demência , Acidente Vascular Cerebral , Humanos , Idoso , Fatores de Risco , Demência/diagnóstico por imagem , Demência/epidemiologia , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Quantitative olfactory assessment has demonstrated clinical utility for the evaluation of a range of neurologic, psychiatric, and sinonasal conditions. Here, we provide age, sex, race, and education-specific normative data for the 12-item Sniffin Sticks Odor Identification Test (SSOIT-12) in older Black and White U.S. adults without preclinical or clinical dementia or sinonasal disease. METHOD: A sample of 2,224 Atherosclerosis Risk in Communities study participants aged 66-89 years were included. A normative regression equation was developed using a linear model for the association of age, sex, race, and education with odor identification score. Regression-based normative mean scores and percentiles were generated by age, sex, race, and education groups. RESULTS: Participants (mean age = 74 years, 59% women, 20% Black, 48% > high school education) had a mean SSOIT-12 score of 9.8. Age, sex, race, and education were all associated with odor identification performance (all ps < .05). A linear regression model for the predicted SSOIT-12 score was developed for use with an individual's actual SSOIT-12 score in order to calculate the Z-score and corresponding percentile for a specific age, sex, race, and education group. Data are also reported in tabular format. CONCLUSIONS: Our study provides SSOIT-12 normative data obtained from a large population of White and Black older adults without preclinical or clinical dementia or sinonasal disease living in the USA. These findings can aid clinicians in assessing the degree of olfactory loss, establishing concordance with a person's perception of olfactory difficulties and quantitatively monitoring changes in olfactory performance over time.
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Olfactory function has significant implications for human health, but few risk factors for olfactory decline have been identified. We examined the factors associated with olfactory status and decline over five years in the Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study. A 12-item odor identification test was used to assess olfaction in 6053 participants in 2011-2013 (ARIC visit 5, mean age: 75.6, 41% male, 23% Black race) and in 3235 participants in 2016-2017 (visit 6). We used Poisson regression models to examine cross-sectional associations of a range of potential factors with the total odor identification errors (mean errors: 2.8 ± 2.4) in visit 5 participants. We used mixed-effect Poisson regression to examine associations with olfactory decline between visits 5 and 6. We also examined associations with visit 5 anosmia prevalence (847 cases, 14%) and incident anosmia between the two visits (510 cases, 16%) using Poisson models. Older age, male sex, lower education, Black race, APOE ε4 alleles, and diabetes were associated with higher odor identification errors and higher anosmia prevalence, and greater physical activity and hypertension with better olfaction. Age, male sex, lower education, Black race, APOE ε4 allele, and vitamin B12 levels were associated with incident anosmia over 5 years. Older age was associated with faster olfactory decline. Future studies with longer follow-ups are warranted.
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Aterosclerose , Olfato , Masculino , Humanos , Idoso , Pré-Escolar , Feminino , Anosmia , Apolipoproteína E4 , Estudos TransversaisRESUMO
BACKGROUND AND OBJECTIVES: Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study. METHODS: Participants were selected from a prospective cohort study of community-dwelling adults; selection criteria included the following: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by 2 diffusion tensor imaging (DTI) measures, fractional anisotropy (FA) and mean diffusivity (MD), and olfaction by a 12-item odor identification test at the same visit. Higher FA and MD values indicate better and worse microstructural integrity, respectively, and higher odor identification scores indicate better olfaction. We used brain region-specific linear regression models to examine associations between DTI measures and olfaction, adjusting for potential confounders. RESULTS: Among 1,418 participants (mean age 76 ± 5 years, 41% male, 21% Black race, 59% with normal cognition), the mean olfaction score was 9 ± 2.3. Relevant to olfaction, higher MD in the medial temporal lobe (MTL) regions, namely the hippocampus (ß -0.79 [95% CI -0.94 to -0.65] units lower olfaction score per 1 SD higher MD), amygdala, entorhinal area, and some white matter (WM) tracts connecting to these regions, was associated with olfaction. We also observed associations with MD and WM FA in multiple atlas regions that were not previously implicated in olfaction. The associations between MD and olfaction were particularly stronger in the MTL regions among individuals with mild cognitive impairment (MCI) compared with those with normal cognition (e.g., ßhippocampus -0.75 [95% CI -1.02 to -0.49] and -0.44 [95% CI -0.63 to -0.26] for MCI and normal cognition, respectively, p interaction = 0.004). DISCUSSION: Neuronal microstructural integrity in multiple brain regions, particularly the MTL (the regions known to be affected in early Alzheimer disease), is associated with odor identification ability. Differential associations in the MTL regions among cognitively normal individuals compared with those with MCI may reflect the earlier vs later effects of the dementia pathogenesis. It is likely that some of the associated regions may not have any functional relevance to olfaction.
Assuntos
Aterosclerose , Demência , Substância Branca , Masculino , Humanos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Imagem de Tensor de Difusão/métodos , Olfato , Estudos Transversais , Estudos Prospectivos , Vida Independente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Demência/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , AnisotropiaRESUMO
Importance: Traumatic brain injury has been associated with short-term olfactory dysfunction, but the association of number of prior head injuries and head injury severity with both subjective and objective long-term olfactory function is less clear. Objective: To investigate the associations of prior head injury, number of prior head injuries, and head injury severity with subjective and psychophysical (objective) olfactory function in older adults and to examine concordance between subjective and objective olfactory function among individuals with and without head injury. Design, Setting, and Participants: This prospective cohort study included 5951 participants who attended Atherosclerosis Risk in Communities (ARIC) Study visit 5 (2011 through 2013). Data analysis was performed between November 2021 and May 2022. Exposures: Head injury was defined by self-report and International Classification of Diseases codes. Main Outcomes and Measures: Self-reported subjective olfactory dysfunction was assessed by the question, "Do you suffer from smell loss or a significantly decreased sense of smell?" Objective olfactory performance was assessed using the 12-item Sniffin' Sticks odor identification test. Results: Overall, the 5951 participants were a mean (SD) age of 75.6 (5.2) years, 3501 (58.8%) were female, 1356 (22.8%) were of Black race, and 1666 (28.0%) had a history of head injury. Participants with prior head injury were more likely than individuals without prior head injury to report subjective olfactory dysfunction (24% vs 20%; difference, 4%; 95% CI, 1% to 6%) and have objective anosmia (15% vs 13%; difference, 2%; 95% CI, 0.1% to 4%) but had lower concordance between subjective and objective assessment (72% vs 77%; difference, -5%; 95% CI, -8% to -3%). In logistic regression models adjusted for sociodemographics and medical comorbidities including cognitive status, participants with a history of prior head injury, particularly individuals with 2 or more prior head injuries and more severe head injuries, were more likely to self-report subjective olfactory dysfunction and were more likely to be found to have objective anosmia compared with participants with no history of head injury. Conclusions and Relevance: Findings of this cohort study provide evidence supporting the association between head injury and olfactory dysfunction, particularly among individuals who experienced multiple prior head injuries and among individuals with more severe head injury. The findings also suggest that individuals with prior head injury were more likely to both under-self-report and over-self-report deficits compared with objective olfactory testing; therefore, it may be important to consider objective olfactory testing in this patient population.
Assuntos
Aterosclerose , Traumatismos Craniocerebrais , Transtornos do Olfato , Idoso , Anosmia , Estudos de Coortes , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/epidemiologia , Feminino , Humanos , Masculino , Transtornos do Olfato/epidemiologia , Estudos Prospectivos , OlfatoRESUMO
Medicare Fee for Service (FFS) claims data, including inpatient (Part A) and outpatient (Part B) services, provide a valuable resource for research on older adults (≥65 year) in linked U.S. cohorts. Here we describe our experience linking the Agricultural Health Study cohort, including 47,501 licensed pesticide applicators and spouses from North Carolina (NC) and Iowa (IA) to Medicare claims data from 1999 to 2016. Given increased Part C (i.e., managed care/Medicare Advantage) enrollment during this period, and a resulting lack of available Part C claims data prior to 2015, we also explored potential for informative missingness. We compared those with partial or limited/no FFS to those with complete FFS coverage (i.e., ≥11 months per year parts AB, but not C, throughout Medicare enrollment) in relation to baseline farm size, general pesticide use, and mortality, in logistic regression models adjusted for age, sex, race, education, and smoking, and stratified by state. While 46,689 participants (98%) were linked to Medicare IDs, only 33,487 (70%) had complete FFS, 9353 (20%) had partial FFS (≥1 year FFS but not complete), and 3849 (8%) had limited/no FFS (Part A or Part C-only). Incomplete FFS was more common in NC, mostly due to Part C, and was associated with farm characteristics, pesticide use, and mortality. These findings indicate that, in addition to reduced sample size in analyses limited to complete FFS, missingness may not be random. The potential impact of incomplete FFS data and changes in coverage type need to be considered when planning linked analyses and interpreting results.