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Jun 10, 2024

Associação do ritmo circadiano com comprometimento cognitivo leve entre homens trabalhadores com pneumoconiose em Hong Kong: um cruzamento

Scientific Reports volume 13, Artigo número: 1650 (2023) Citar este artigo

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Os ritmos de atividade circadiana (CARs) enfraquecidos foram associados ao comprometimento cognitivo leve (MCI) na população em geral. No entanto, ainda não está claro entre pacientes com pneumoconiose. Nosso objetivo era abordar essa lacuna de conhecimento. Este estudo transversal incluiu 186 pacientes do sexo masculino com pneumoconiose (71,3 ± 7,8 anos) e 208 homens saudáveis ​​da comunidade. A actigrafia foi utilizada para determinar os parâmetros do CAR (porcentagem de ritmo, amplitude, MESOR e acrofase). Valores abaixo das medianas correspondentes dos parâmetros dos CARs representaram CARs enfraquecidos. A versão cantonesa do Mini Exame do Estado Mental (CMMSE) foi usada para avaliar a função cognitiva, o MCI e o resultado composto do MCI mais o comprometimento cognitivo. Em comparação com os referentes da comunidade, os pacientes com pneumoconiose apresentaram pior cognição e redução dos CARs. Em comparação com os referentes da comunidade ou pacientes com pneumoconiose com ritmo circadiano robusto, os pacientes com pneumoconiose com ritmo circadiano enfraquecido foram consistentemente associados ao aumento do risco de CCL e ao desfecho composto. No entanto, associação significativa foi observada apenas entre MESOR e o desfecho composto (OR ajustado = 1,99, 95%: 1,04–3,81). Uma fase tardia de CARs foi associada de forma insignificante ao MCI e ao desfecho composto. Nossas descobertas mostraram que CARs enfraquecidos estavam associados a pior função cognitiva entre trabalhadores do sexo masculino com pneumoconiose. A intervenção na melhoria dos CARs pode mitigar a deterioração cognitiva em trabalhadores do sexo masculino com pneumoconiose.

Pneumoconiosis is the most common interstitial occupational lung disease, mainly including silicosis, asbestosis, and coal workers' pneumoconiosis1. Globally, 251,299 workers died from pneumoconiosis in 1990, and the death toll slightly rose to 259,700 in 20132. In Hong Kong, silicosis has been ranked as the top third occupational disease, which along with asbestosis, has constantly contributed to 19.4% of overall prescribed occupational diseases over the last decade (2009 ~ 2019) (2019)." href="/articles/s41598-023-28832-5#ref-CR3" id="ref-link-section-d63416991e483"> 3. O desenvolvimento de fibrose pulmonar pode continuar mesmo após a cessação da exposição ao pó durante muitos anos. Alguns trabalhadores com pneumoconiose podem sofrer de hipoxemia – inflamação, estresse oxidativo – parênquima cerebral e alterações vasculares4. Evidências da população idosa em geral e de pacientes com doenças pulmonares obstrutivas crônicas (DPOC) mostraram que essas alterações patológicas estavam associadas ao desenvolvimento de atrofia do hipocampo e a um nível elevado de proteína β-amilóide no cérebro5,6, que são marcadores evidentes de declínio cognitivo e comprometimento cognitivo7.

Enquanto isso, como a pneumoconiose é uma doença pulmonar restritiva típica, os trabalhadores com pneumoconiose também podem encontrar distúrbios do sono e má qualidade do sono resultantes da tosse noturna e dificuldades respiratórias relacionadas. A interrupção do sono pode fazer com que os pacientes com pneumoconiose fiquem expostos a mais luz durante a noite e à inatividade física, perturbando o ritmo circadiano. O ritmo circadiano é crucial para que os mamíferos mantenham a sincronia entre a fisiologia interna, o comportamento e o ambiente flutuante externo8. A perda desta sincronia pode causar desalinhamento circadiano e levar ainda a uma série de resultados adversos para a saúde, incluindo doenças cardiometabólicas9, doenças inflamatórias10, cancro11 e doenças neurodegenerativas12. Pesquisas recentes na população idosa em geral suscitaram grande interesse numa associação positiva entre perturbação do ritmo circadiano e comprometimento cognitivo13,14,15. Intervenções destinadas a melhorar os ritmos circadianos, como a fototerapia16, o suplemento de melatonina17 e a promoção do exercício físico18, demonstraram potenciais efeitos benéficos na prevenção do declínio cognitivo.

 6 years. Marital status was classified as single/divorced/widowed or married/cohabitating. Employment status was categorized as retired or employed. Smoking status was categorized as never smoker, former smoker, and current smoker. A never smoker referred to one who had never smoked as much as 20 packs of cigarettes or 12 oz of tobacco in a lifetime, or 1 cigarette a day or 1 cigar a week for 1 year. If a smoker had quit smoking for 1 year or more, he was considered a former smoker 21; otherwise, he was considered a current smoker. Alcohol drinking was classified as never drinker, former drinker, and current drinker. A never drinker referred to one who had never drunk as much as once per month and had been lasting over half a year. A drinker was defined if he or she drank alcohol at least once per month and had been lasting over half a year. If the drinker had quit drinking for 1 year or more, he was considered a former drinker; otherwise, he was a current drinker. Participants who drank tea or coffee more than twice weekly for at least 6 months were defined as tea drinkers or coffee drinkers, respectively. Anxious and depressive symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS)22. Both anxiety and depression were categorized as normal (0–7), borderline abnormal (8–10), and abnormal (11–21). Physical activity was assessed with the short interviewer-administrated International Physical Activity Questionnaire (IPAQ) and was categorized as low, moderate, and high23. Subjective sleep quality was examined by the Pittsburgh Sleep Quality Index (PSQI), and a poor sleeper was defined if his/her PSQI score was > 524. Waist circumference was measured at the midpoint between the lowest rib and the iliac crest25. Handgrip strength was measured by the hydraulic hand dynamometer (Jamar; Lafayette, USA). The maximal handgrip strength measurement from a single trial on either hand was included in the analyses26./p>

Mild cognitive impairment (MCI) is a cognitive decline greater than expected for an individual's age and education level but without notable interference in daily activities27. It is a preclinical status between normal cognition to cognitive impairment. The CMMSE was used to measure the cognitive function of the study participants. The CMMSE has been translated and validated by Chiu et al. to assess dementia among Hong Kong Chinese28, which contains 30 items to measure various cognitive domains, including orientation, registration, attention and calculation, immediate and short-term recall, and language, with a score ranging from 0 to 30. A lower CMMSE score indicates a worse cognitive function of the participant. We adopted the cut-off levels of CMMSE proposed in a previous study (2012)." href="/articles/s41598-023-28832-5#ref-CR29" id="ref-link-section-d63416991e625"29 to define the cognitive status, i.e., 27–30, 21–26, 0–20 were mutually exclusively categorized as normal cognition, MCI, and cognitive impairment (which also means "moderate-severe cognitive impairment"), respectively./p> 7th, 7th-2nd, and ≤ 2nd percentile was determined as normal cognition, MCI, and cognitive impairment, respectively32. Since no percentile cutoff scores were reported for subjects < 65 years old in the manual, subjects in this age stratum were referred to the percentile scores of the 65–69 age stratum in this study./p>

Each pneumoconiosis worker and community subject continuously wore a GENEActiv Original (Activinsights Company, UK) device on his non-dominant wrist for 168 h without removal, even during sleep or bathing (measurement frequency 100 Hz, sampling rate corresponding to 1 min). The assessment of circadian rhythm parameters had been described previously33. The actigraphy detects and records movements in three mutually vertical axes (x, y, and z) and real-time skin temperature. A gravity-subtracted sum of vector magnitudes (SVM) was automatically calculated with data of the three axes (x, y, and z) and a formula defined by the manufacturer: SVMg s = [(x2 + y2 + z2)½—1 g]." href="/articles/s41598-023-28832-5#ref-CR34" id="ref-link-section-d63416991e665"34. Non-wearing time was determined by reviewing the activity records outputted from the GENEActiv software and self-reported by the interviewees. The non-wearing periods should present low and steady SVM readings. For each participant, the data of non-wearing periods were excluded from the calculation of their parameters. The recordings lasted from 5 to 7 consecutive days, including a weekend. If the sum length of wearing was less than 120 h (5/7 of 168 h), the wearing was considered incomplete, and its data were not analyzed./p> 5), waist circumference, and handgrip strength. The covariates were selected based on the conceptual definition of confounding and referred to previous literature with similar study purposes./p>

This study has several limitations. First, the cross-sectional design of this study may limit us from causal inference. However, this study added value to the scientific literature as evidence of circadian rhythm and the cognitive outcome is very limited in pneumoconiosis patients. Second, sixty community subjects in the study were recruited between June 23 to July 09, 2020, just after the 2nd wave of the COVID-19 outbreak in Hong Kong (2020)." href="/articles/s41598-023-28832-5#ref-CR46" id="ref-link-section-d63416991e4184"46. The possible physical inactivity due to sustained quarantine and social distancing47 may adversely influence participants' circadian rhythm. We performed a sensitivity analysis excluding the community subjects recruited within this period. A significantly decreased amplitude was observed in pneumoconiosis patients compared to that of the community subjects (as shown in Supplementary Table S2). Thus, the overall circadian activity of the community referents may be underestimated. However, we expected this would have biased our findings toward the null. Third, we used medians as cut-offs for each circadian rhythm parameter because there are no standard criteria to define weak and robust circadian rhythm. Meanwhile, the sample size restricted us from further dividing participants into tertiles or quartiles of circadian rhythm parameters to investigate the biological gradient (dose–response) of circadian disruption. According to their self-reported disease history, there were no patients with any lung diseases in our community referents. Thus, we could not compare the major outcomes between community residents with or without other lung diseases. We used the composite outcome of MCI plus cognitive impairment as the primary outcome to improve statistical power. Finally, all our study participants were men, so the generalization to the whole population, including women, could be limited./p> (2019)./p>

(2012)./p>./p> (2020)./p>

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