Associazione del ritmo circadiano con lieve deterioramento cognitivo tra i lavoratori maschi affetti da pneumoconiosi a Hong Kong: una croce

Rapporti scientifici volume 13, numero articolo: 1650 (2023) Citare questo articolo

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L’indebolimento dei ritmi di attività circadiana (CAR) è stato associato a un lieve deterioramento cognitivo (MCI) nella popolazione generale. Tuttavia, rimane poco chiaro tra i pazienti affetti da pneumoconiosi. Il nostro obiettivo è colmare questa lacuna di conoscenza. Questo studio trasversale comprendeva 186 pazienti maschi affetti da pneumoconiosi (71,3 ± 7,8 anni) e 208 uomini sani della comunità. L'attigrafia è stata utilizzata per determinare i parametri dei CAR (ritmo percentuale, ampiezza, MESOR e acrofase). I valori inferiori alle mediane corrispondenti dei parametri CAR rappresentavano CAR indeboliti. La versione cantonese del Mini-Mental State Examination (CMMSE) è stata utilizzata per valutare la funzione cognitiva, il MCI e l'esito composito del MCI più il deterioramento cognitivo. Rispetto ai referenti della comunità, i pazienti affetti da pneumoconiosi avevano condizioni cognitive peggiori e CAR attenuati. Rispetto ai referenti della comunità o ai pazienti con pneumoconiosi con ritmo circadiano robusto, i pazienti con pneumoconiosi con ritmo circadiano indebolito erano costantemente associati ad un aumento del rischio di MCI e all’esito composito. Tuttavia, è stata osservata un'associazione significativa solo tra MESOR e l'esito composito (OR aggiustato = 1,99, 95%: 1,04–3,81). Una fase ritardata dei CAR era associata in modo insignificante al MCI e all’esito composito. I nostri risultati hanno mostrato che i CAR indeboliti erano associati a una peggiore funzione cognitiva tra i lavoratori maschi affetti da pneumoconiosi. L’intervento nel miglioramento dei CAR può mitigare il deterioramento cognitivo nei lavoratori maschi affetti da pneumoconiosi.

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. Lo sviluppo della fibrosi polmonare potrebbe continuare anche dopo che l'esposizione alla polvere è cessata da molti anni. Alcuni operatori affetti da pneumoconiosi possono soffrire di ipossiemia (infiammazione, stress ossidativo), alterazioni del parenchima cerebrale e vascolari4. Le prove provenienti dalla popolazione anziana generale e dai pazienti con malattie polmonari croniche ostruttive (BPCO) hanno dimostrato che questi cambiamenti patologici erano associati allo sviluppo di atrofia dell'ippocampo e a un livello elevato di proteina amiloide-β nel cervello5,6, che sono evidenti marcatori di Declino cognitivo e deterioramento cognitivo7.

Nel frattempo, poiché la pneumoconiosi è una tipica malattia polmonare restrittiva, i lavoratori affetti da pneumoconiosi possono anche riscontrare disturbi del sonno e una scarsa qualità del sonno derivanti dalla tosse notturna e dalle difficoltà respiratorie correlate. L’interruzione del sonno può causare ai pazienti affetti da pneumoconiosi un’esposizione a più luce durante la notte e all’inattività fisica, interrompendo il loro ritmo circadiano. Il ritmo circadiano è fondamentale per i mammiferi per mantenere la sincronia tra la fisiologia interna, il comportamento e le fluttuazioni dell'ambiente esterno8. La perdita di questa sincronia potrebbe causare un disallineamento circadiano e portare ulteriormente a una serie di esiti avversi per la salute, tra cui malattie cardiometaboliche9, malattie infiammatorie10, cancro11 e malattie neurodegenerative12. Recenti ricerche sulla popolazione anziana generale hanno suscitato grande interesse per un'associazione positiva tra interruzione del ritmo circadiano e deterioramento cognitivo13,14,15. Gli interventi mirati a migliorare i ritmi circadiani, come la terapia della luce16, l'integrazione di melatonina17 e la promozione dell'esercizio fisico18, hanno mostrato potenziali effetti benefici sulla prevenzione del declino 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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Associazione del ritmo circadiano con lieve deterioramento cognitivo tra i lavoratori maschi affetti da pneumoconiosi a Hong Kong: una croce