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INTRODUCTION: Diabetes is linked to neurodegenerative diseases (NDs), but data in type 1 diabetes are scarce. Our aim was to assess the standardized incidence ratios (SIRs) of different NDs in type 1 diabetes, and to evaluate the impact of diabetic vascular complications and age at diabetes onset. RESEARCH DESIGN AND METHODS: In this observational cohort study, we included 4261 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy study, and 11 653 matched population-based controls without diabetes. NDs were identified from registers until the end of 2017. Diabetic complications were assessed at the baseline study visit. SIRs were calculated from diabetes onset, except for impact of complications that was calculated from baseline study visit. RESULTS: The SIRs for NDs were increased in type 1 diabetes: any dementia 2.24 (95% CI 1.79 to 2.77), Alzheimer's disease 2.13 (95% CI 1.55 to 2.87), vascular dementia 3.40 (95% CI 2.08 to 5.6), other dementias 1.70 (95% CI 1.22 to 2.31), and Parkinson's disease 1.61 (95% CI 1.04 to 2.37). SIR showed a twofold increased incidence already in those without albuminuria (1.99 (1.44-2.68)), but further increased in presence of diabetic complications: kidney disease increased SIR for Alzheimer's disease, while cardiovascular disease increased SIR for both Alzheimer's disease and other dementias. Diabetes onset <15 years, compared with ≥15 years, increased SIR of Alzheimer's disease, 3.89 (2.21-6.35) vs 1.73 (1.16-2.48), p<0.05, but not the other dementias. CONCLUSIONS: ND incidence is increased 1.7-3.4-fold in type 1 diabetes. The presence of diabetic kidney disease and cardiovascular disease further increased the incidence of dementia.
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Diabetes Mellitus Tipo 1 , Enfermedades Neurodegenerativas , Humanos , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Finlandia/epidemiología , Masculino , Femenino , Incidencia , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/complicaciones , Persona de Mediana Edad , Adulto , Estudios de Seguimiento , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Factores de Riesgo , Nefropatías Diabéticas/epidemiologíaRESUMEN
BACKGROUND: Long-term exposure to ambient air pollution has been linked with all-cause mortality and cardiovascular and respiratory diseases. Suggestive associations between ambient air pollutants and neurodegeneration have also been reported, but due to the small effect and relatively rare outcomes evidence is yet inconclusive. Our aim was to investigate the associations between long-term air pollution exposure and mortality from neurodegenerative diseases. METHODS: A Dutch national cohort of 10.8 million adults aged ≥30 years was followed from 2013 until 2019. Annual average concentrations of air pollutants (ultra-fine particles (UFP), nitrogen dioxide (NO2), fine particles (PM2.5 and PM10) and elemental carbon (EC)) were estimated at the home address at baseline, using land-use regression models. The outcome variables were mortality due to amyotrophic lateral sclerosis (ALS), Parkinson's disease, non-vascular dementia, Alzheimer's disease, and multiple sclerosis (MS). Hazard ratios (HR) were estimated using Cox models, adjusting for individual and area-level socio-economic status covariates. RESULTS: We had a follow-up of 71 million person-years. The adjusted HRs for non-vascular dementia were significantly increased for NO2 (1.03; 95% confidence interval (CI) 1.02-1.05) and PM2.5 (1.02; 95%CI 1.01-1.03) per interquartile range (IQR; 6.52 and 1.47 µg/m3, respectively). The association with PM2.5 was also positive for ALS (1.02; 95%CI 0.97-1.07). These associations remained positive in sensitivity analyses and two-pollutant models. UFP was not associated with any outcome. No association with air pollution was found for Parkinson's disease and MS. Inverse associations were found for Alzheimer's disease. CONCLUSION: Our findings, using a cohort of more than 10 million people, provide further support for associations between long-term exposure to air pollutants (PM2.5 and particularly NO2) and mortality of non-vascular dementia. No associations were found for Parkinson and MS and an inverse association was observed for Alzheimer's disease.
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Contaminantes Atmosféricos , Contaminación del Aire , Exposición a Riesgos Ambientales , Enfermedades Neurodegenerativas , Material Particulado , Humanos , Países Bajos/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Masculino , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Enfermedades Neurodegenerativas/mortalidad , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/epidemiología , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Exposición a Riesgos Ambientales/efectos adversos , Anciano , Material Particulado/análisis , Material Particulado/efectos adversos , AdultoRESUMEN
BACKGROUND AND OBJECTIVES: Accumulating evidence connects diverse components of body composition (e.g., fat, muscle, and bone) to neurodegenerative disease risk, yet their interplay remains underexplored. This study examines the associations between patterns of body composition and the risk of neurodegenerative diseases, exploring the mediating role of cardiovascular diseases (CVDs). METHODS: This retrospective analysis used data from the UK Biobank, a prospective community-based cohort study. We included participants free of neurodegenerative diseases and with requisite body composition measurements at recruitment, who were followed from 5 years after recruitment until April 1, 2023, to identify incident neurodegenerative diseases. We assessed the associations between different components and major patterns of body composition (identified by principal component analysis) with the risk of neurodegenerative diseases, using multivariable Cox models. Analyses were stratified by disease susceptibility, indexed by polygenetic risk scores for Alzheimer and Parkinson diseases, APOE genotype, and family history of neurodegenerative diseases. Furthermore, we performed mediation analysis to estimate the contribution of CVDs to these associations. In addition, in a subcohort of 40,790 participants, we examined the relationship between body composition patterns and brain aging biomarkers (i.e., brain atrophy and cerebral small vessel disease). RESULTS: Among 412,691 participants (mean age 56.0 years, 55.1% female), 8,224 new cases of neurodegenerative diseases were identified over an average follow-up of 9.1 years. Patterns identified as "fat-to-lean mass," "muscle strength," "bone density," and "leg-dominant fat distribution" were associated with a lower rate of neurodegenerative diseases (hazard ratio [HR] = 0.74-0.94) while "central obesity" and "arm-dominant fat distribution" patterns were associated with a higher rate (HR = 1.13-1.18). Stratification analysis yielded comparable risk estimates across different susceptibility groups. Notably, 10.7%-35.3% of the observed associations were mediated by CVDs, particularly cerebrovascular diseases. The subcohort analysis of brain aging biomarkers corroborated the findings for "central obesity," "muscle strength," and "arm-dominant fat distribution" patterns. DISCUSSION: Our analyses demonstrated robust associations of body composition patterns featured by "central obesity," "muscle strength," and "arm-dominant fat distribution" with both neurodegenerative diseases and brain aging, which were partially mediated by CVDs. These findings underscore the potential of improving body composition and early CVD management in mitigating risk of neurodegenerative diseases.
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Composición Corporal , Enfermedades Cardiovasculares , Enfermedades Neurodegenerativas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Neurodegenerativas/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Biobanco del Reino Unido , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. METHODS: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. RESULTS: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. CONCLUSIONS: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.
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Benzodiazepinas , Demencia , Humanos , Femenino , Demencia/epidemiología , Demencia/inducido químicamente , Masculino , Anciano , Benzodiazepinas/efectos adversos , Benzodiazepinas/administración & dosificación , Persona de Mediana Edad , Imagen por Resonancia Magnética , Países Bajos/epidemiología , Anciano de 80 o más Años , Neuroimagen , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/patología , Estudios Prospectivos , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/inducido químicamente , Hipnóticos y Sedantes/efectos adversos , Factores de RiesgoRESUMEN
The health and well-being of retired rugby union and league players, particularly regarding the long-term effects of concussions, are of major concern. Concussion has been identified as a major risk factor for neurodegenerative diseases, such as Alzheimer's and Amyotrophic Lateral Sclerosis (ALS), in athletes engaged in contact sports. This study aimed to assess differences in specific biomarkers between UK-based retired rugby players with a history of concussion and a non-contact sports group, focusing on biomarkers associated with Alzheimer's, ALS, and CTE. We randomly selected a sample of male retired rugby or non-contact sport athletes (n = 56). The mean age was 41.84 ± 6.44, and the mean years since retirement from the sport was 7.76 ± 6.69 for participants with a history of substantial concussions (>5 concussions in their career) (n = 30). The mean age was 45.75 ± 11.52, and the mean years since retirement was 6.75 ± 4.64 for the healthy controls (n = 26). Serum biomarkers (t-tau, RBP-4, SAA, Nf-L, and retinol), plasma cytokines, and biomarkers associated with serum-derived exosomes (Aß42, p-tau181, p-tau217, and p-tau231) were analyzed using validated commercial ELISA assays. The results of the selected biomarkers were compared between the two groups. Biomarkers including t-tau and p-tau181 were significantly elevated in the history of the substantial concussion group compared to the non-contact sports group (t-tau: p < 0.01; p-tau181: p < 0.05). Although between-group differences in p-tau217, p-tau231, SAA, Nf-L, retinol, and Aß42 were not significantly different, there was a trend for higher levels of Aß42, p-tau217, and p-tau231 in the concussed group. Interestingly, the serum-derived exosome sizes were significantly larger (p < 0.01), and serum RBP-4 levels were significantly reduced (p < 0.05) in the highly concussed group. These findings indicate that retired athletes with a history of multiple concussions during their careers have altered serum measurements of exosome size, t-tau, p-tau181, and RBP-4. These biomarkers should be explored further for the prediction of future neurodegenerative outcomes, including ALS, in those with a history of concussion.
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Atletas , Biomarcadores , Conmoción Encefálica , Fútbol Americano , Enfermedades Neurodegenerativas , Jubilación , Humanos , Biomarcadores/sangre , Masculino , Conmoción Encefálica/sangre , Conmoción Encefálica/epidemiología , Persona de Mediana Edad , Reino Unido/epidemiología , Fútbol Americano/lesiones , Adulto , Enfermedades Neurodegenerativas/sangre , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/etiología , Rugby , Proteínas tau/sangre , Factores de Riesgo , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Traumatismos en Atletas/sangre , Traumatismos en Atletas/epidemiologíaRESUMEN
Importance: Vision and eye conditions are associated with increased risk for Alzheimer disease and related dementias (ADRDs), but the nature of the association and the underlying biological pathways remain unclear. If causal, vision would be an important modifiable risk factor with viable population-level interventions. Objective: To evaluate potentially causal associations between visual acuity, eye conditions (specifically cataracts and myopia), neuroimaging outcomes, and ADRDs. Design, Setting, and Participants: A cohort and 2-sample bidirectional mendelian randomization (MR) study was conducted using UK Biobank participants and summary statistics from previously published genome-wide association studies on cataract, myopia, and AD. The participants included in the analysis were aged 55 to 70 years without dementia at baseline (calendar years 2006 to 2010), underwent genotyping, and reported on eye conditions; a subset completed visual acuity examinations (n = 69 852-71 429) or brain imaging (n = 36â¯591-36 855). Data were analyzed from August 15, 2022, through November 28, 2023. Exposure: Self-reported cataracts, visual acuity, and myopia measured by refraction error. Main Outcomes and Measures: ADRD, AD, and vascular dementia were identified from electronic medical records. Total and regional brain volumes were determined using magnetic resonance imaging. Results: The sample included 304â¯953 participants (mean [SD] age, 62.1 (4.1) years; 163â¯825 women [53.72%]); 14â¯295 (4.69%) had cataracts and 2754 (3.86%) had worse than 20/40 vision. Cataracts (hazard ratio [HR], 1.18; 95% CI, 1.07-1.29) and myopia (HR, 1.35; 95% CI, 1.06-1.70) were associated with a higher hazard of ADRD. In MR analyses to estimate potential causal effects, cataracts were associated with increased risk of vascular dementia (inverse variance-weighted odds ratio [OR], 1.92; 95% CI, 1.26-2.92) but were not associated with increased dementia (OR, 1.21; 95% CI, 0.98-1.50). There were no associations between myopia and dementia. In MR for potential reverse causality, AD was not associated with cataracts (inverse variance-weighted OR, 0.99; 95% CI, 0.96-1.01). Genetic risk for cataracts was associated with smaller total brain (ß = -597.43 mm3; 95% CI, -1077.87 to -117.00 mm3) and gray matter (ß = -375.17 mm3; 95% CI, -680.10 to -70.24 mm3) volumes, but not other brain regions. Conclusions and Relevance: In this cohort and MR study of UK Biobank participants, cataracts were associated with increased risk of dementia, especially vascular dementia, and reduced total brain volumes. These findings lend further support to the hypothesis that cataract extraction may reduce the risk for dementia.
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Catarata , Demencia , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Catarata/epidemiología , Demencia/epidemiología , Demencia/genética , Miopía/epidemiología , Miopía/genética , Factores de Riesgo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiología , Trastornos de la Visión/epidemiología , Análisis de la Aleatorización Mendeliana , Reino Unido/epidemiología , Estudios de Cohortes , Agudeza Visual , Estudio de Asociación del Genoma Completo , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/genéticaRESUMEN
Several studies have demonstrated a correlation between neurodegenerative diseases (NDDs) and myocardial infarction (MI), yet the precise causal relationship between these remains elusive. This study aimed to investigate the potential causal associations of genetically predicted Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and multiple sclerosis (MS) with MI using two-sample Mendelian randomization (TSMR). Various methods, including inverse variance weighted (IVW), weighted median (WM), MR-Egger regression, weighted mode, and simple mode, were employed to estimate the effects of genetically predicted NDDs on MI. To validate the analysis, we assessed pleiotropic effects, heterogeneity, and conducted leave-one-out sensitivity analysis. We identified that genetic predisposition to NDDs was suggestively associated with higher odds of MI (OR_IVW=1.07, OR_MR-Egger=1.08, OR_WM=1.07, OR_weighted mode=1.07, OR_simple mode=1.10, all P<0.05). Furthermore, we observed significant associations of genetically predicted DLB with MI (OR_IVW=1.07, OR_MR-Egger=1.11, OR_WM=1.09, OR_weighted mode=1.09, all P<0.05). However, there was no significant causal evidence of genetically predicted PD and MS in MI. Across all MR analyses, no horizontal pleiotropy or statistical heterogeneity was observed (all P>0.05). Additionally, results from MRPRESSO and leave-one-out sensitivity analysis confirmed the robustness of the causal effect estimations for genetically predicted AD, DLB, PD, and MS on MI. This study provides further support for the causal effects of AD on MI and, for the first time, establishes robust causal evidence for the detrimental effect of DLB on the risk of MI. Our findings emphasize the importance of monitoring the cardiovascular function of the elderly experiencing neurodegenerative changes.
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Predisposición Genética a la Enfermedad , Análisis de la Aleatorización Mendeliana , Infarto del Miocardio , Enfermedades Neurodegenerativas , Humanos , Infarto del Miocardio/genética , Infarto del Miocardio/epidemiología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/epidemiología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiología , Factores de Riesgo , Polimorfismo de Nucleótido Simple , CausalidadRESUMEN
Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.
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Demencia , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Estudios Retrospectivos , China/epidemiología , Persona de Mediana Edad , Anciano , Demencia/epidemiología , Demencia/etiología , Progresión de la Enfermedad , Enfermedad de Alzheimer/epidemiología , Neurosífilis/epidemiología , Neurosífilis/complicaciones , Síndrome de Creutzfeldt-Jakob/epidemiología , Demencia Frontotemporal/epidemiología , Encefalitis/epidemiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Anciano de 80 o más Años , Enfermedades Neurodegenerativas/epidemiologíaRESUMEN
This scoping review aims at giving an overview of the possible influence of neurodevelopmental disorders (NDDs) on cognitive-behavioral neurodegenerative diseases (CBNDs). Based on the PRISMA-ScR checklist, it details the methods of NDDs screening, the identified NDDs-CBNDs associations, as well as the criteria and types of association. The last literature search was performed in June 2023. In the final study, 32 articles were included. Analysis first showed that NDDs were mainly detected through medical records screening. Second, the association of specific learning disorders and major or mild neurocognitive disorder due to Alzheimer's disease was the most investigated. Third, associations were mostly based on prevalence comparisons. Finally, 66â¯% of studies reported a positive association between NDDs and CBNDs. Notably, up to 67â¯% of positive associations were observed with atypical forms of certain CBNDs. Authors' interpretations suggest that NDDs could constitute a risk factor for CBNDs. However, the influence of NDDs on CBNDs still lacks evidence and biological support, possibly due to the heterogeneity of methods and criteria employed. Developing validated assessment tools for all NDDs and conducting cohort studies could be beneficial for research, and clinical practice. Indeed, this review also underlines the importance of adopting a life-span approach regarding CBNDs.
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Enfermedades Neurodegenerativas , Trastornos del Neurodesarrollo , Humanos , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/psicología , Enfermedades Neurodegenerativas/diagnóstico , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/diagnósticoRESUMEN
Background: Aging has always been considered as a risk factor for neurodegenerative diseases, but there are individual differences and its mechanism is not yet clear. Epigenetics may unveil the relationship between aging and neurodegenerative diseases. Methods: Our study employed a bidirectional two-sample Mendelian randomization (MR) design to assess the potential causal association between epigenetic aging and neurodegenerative diseases. We utilized publicly available summary datasets from several genome-wide association studies (GWAS). Our investigation focused on multiple measures of epigenetic age as potential exposures and outcomes, while the occurrence of neurodegenerative diseases served as potential exposures and outcomes. Sensitivity analyses confirmed the accuracy of the results. Results: The results show a significant decrease in risk of Parkinson's disease with GrimAge (OR = 0.8862, 95% CI 0.7914-0.9924, p = 0.03638). Additionally, we identified that HannumAge was linked to an increased risk of Multiple Sclerosis (OR = 1.0707, 95% CI 1.0056-1.1401, p = 0.03295). Furthermore, we also found that estimated plasminogen activator inhibitor-1(PAI-1) levels demonstrated an increased risk for Alzheimer's disease (OR = 1.0001, 95% CI 1.0000-1.0002, p = 0.04425). Beyond that, we did not observe any causal associations between epigenetic age and neurodegenerative diseases risk. Conclusion: The findings firstly provide evidence for causal association of epigenetic aging and neurodegenerative diseases. Exploring neurodegenerative diseases from an epigenetic perspective may contribute to diagnosis, prognosis, and treatment of neurodegenerative diseases.
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Envejecimiento , Epigénesis Genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedades Neurodegenerativas , Humanos , Envejecimiento/genética , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/epidemiología , Predisposición Genética a la Enfermedad , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiología , Inhibidor 1 de Activador Plasminogénico/genética , Factores de Riesgo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/epidemiologíaRESUMEN
Objective: Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders. Methods: We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model. Results: The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001). Interpretation: These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden. Systematic Review Registration: PROSPERO (CRD42023437553).
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Enfermedades Inflamatorias del Intestino , Enfermedades Neurodegenerativas , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/etiología , Estudios Longitudinales , Factores de Riesgo , Estudios ProspectivosRESUMEN
Background: People are living longer but an increasing number of older people experience chronicity and disability in the latest years of their life. The Marche region is one of the Italian regions where people live the longest lives; therefore, the number of people with age-related chronic diseases is expected to be at least similar, if not higher, compared to the rest of Italy. The identification of the aging trajectories is of huge interest in the arena of public health. Administrative healthcare databases represent valuable reservoirs for reconstructing the trajectories of aging. Here, we present the protocol for a study (TREND project) aimed to integrate existing administrative databases into a Marche regional dataset in order to estimate the prevalence and incidence rates of age-related neurodegenerative diseases (ND), with a specific focus on Parkinsonism and Dementia. Methods: The TREND Project is a retrospective cross-sectional study. The source population includes permanent residents in the Marche region aged 40 years and older. A minimal dataset has been built up linking data on drug prescriptions, outpatient services, and diagnosis for hospital admission, from 2014 to 2021 in the Marche Region. Data on clinical outcomes (re-hospitalization, mortality, comorbidities), and therapeutic approaches (drugs and medicines) have been integrated with state-of-the-art statistical methods to define patients into different risk clusters and to analyze the aging trend by assessing the Comorbidity Index (CI) as a proxy for chronicity. Discussion: Our research contributes to the integration of existing administrative databases on ND to create a Marche regional ND database, support regional health policy, and better understand patients' needs and their aging trajectories. This approach could be implemented also at the National level. Moreover, by linking different administrative data sources, this study sheds light on important issues related to ND, such as early-onset dementia; ethical aspects such as anticipated wills; problems of dementia in patients still in the job market, etc. The results of this study will contribute to the successful implementation of integrated care for patients affected by ND at regional or national levels.
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Envejecimiento , Bases de Datos Factuales , Enfermedades Neurodegenerativas , Humanos , Italia/epidemiología , Enfermedades Neurodegenerativas/epidemiología , Anciano , Estudios Transversales , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedad Crónica/epidemiología , Masculino , Adulto , Anciano de 80 o más Años , Prevalencia , Incidencia , Demencia/epidemiologíaRESUMEN
OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.
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Neoplasias , Enfermedades no Transmisibles , Exposición Profesional , Humanos , Exposición Profesional/efectos adversos , Exposición Profesional/estadística & datos numéricos , Exposición Profesional/análisis , Enfermedades no Transmisibles/epidemiología , Neoplasias/epidemiología , Neoplasias/etiología , Factores de Riesgo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/etiología , Exposoma , Trastornos Mentales/epidemiología , Trastornos Mentales/etiologíaRESUMEN
BACKGROUND: Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths. METHODS: This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. RESULTS: During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. CONCLUSION: Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Ácido Úrico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/epidemiología , Estudios de Cohortes , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/sangre , Enfermedades Neurodegenerativas/epidemiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/epidemiología , Estudios Prospectivos , Biobanco del Reino Unido , Reino Unido/epidemiología , Ácido Úrico/sangreRESUMEN
Background: Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer's disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and management difficulties. Objective: This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods: A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results: Psychosis is a frequently observed phenomenon during the course of ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6-78.3%) and visual hallucinations (50-69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1-60.3% and 3.10-41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions: Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues.
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Trastornos Psicóticos , Humanos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/psicología , Enfermedades Neurodegenerativas/diagnóstico , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/psicología , Enfermedad por Cuerpos de Lewy/epidemiología , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/epidemiología , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/complicaciones , Deluciones/diagnóstico , Deluciones/epidemiología , Deluciones/etiología , Demencia/epidemiología , Demencia/diagnósticoRESUMEN
BACKGROUND: Neurodegenerative diseases are a group of unexplained disorders of the central nervous system, and studies have shown that a large number of genetic and environmental factors are associated with these diseases. Since these diseases show significant gender differences in epidemiology, sex hormones are thought to be strongly associated with these diseases. In this study, we used Mendelian randomization to explore the causal relationship between sex hormones and the risk of developing neurodegenerative diseases. METHODS: We obtained genetic instrumental variables for sex hormones (sex hormone-binding globulin [SHBG], estradiol levels [EL], and bioavailable testosterone [BT]) separately through the Integrative Epidemiology Unit (IEU) database (https://gwas.mrcieu.ac.uk/). We analyzed the causal relationship of each with the risk of developing neurodegenerative diseases (Amyotrophic Lateral Sclerosis [ALS], Parkinson's disease [PD], and Alzheimer's disease [AD]) using inverse variance weighted (IVW) in Mendelian randomization. Data were then analyzed for sensitivity. RESULTS: BT was negatively associated with the risk of developing ALS (odds ratio [OR] = 0.794; 95% confidence interval [95% CI] = 0.672-0.938; p = 0.006). EL and SHBG were not associated with a risk for developing neurodegenerative diseases (ALS, PD, AD). CONCLUSIONS: Elevated BT is associated with a reduced risk of developing ALS. Further research is needed to investigate the underlying mechanisms of action for this correlation and how it can be used as a potential target of action to reduce the risk of developing ALS.
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Análisis de la Aleatorización Mendeliana , Enfermedades Neurodegenerativas , Globulina de Unión a Hormona Sexual , Humanos , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/genética , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangre , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Estradiol/sangre , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/epidemiología , Hormonas Esteroides Gonadales/sangre , Hormonas Esteroides Gonadales/metabolismo , Femenino , MasculinoRESUMEN
The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer's disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson's disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as Porphyromonas gingivalis. Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged.
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Enfermedades Neurodegenerativas , Periodontitis , Humanos , Periodontitis/complicaciones , Periodontitis/epidemiología , Factores de Riesgo , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/etiología , Enfermedad de Parkinson/epidemiología , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/epidemiologíaRESUMEN
The following commentary discusses a review by Cressot et al. entitled: 'Psychosis in Neurodegenerative Dementias: A Systematic Comparative Review'. The authors describe the epidemiology and phenomenology of psychosis across neurodegenerative dementias. Dementia with Lewy bodies had the highest reported prevalence of psychosis at 74% followed by Alzheimer's disease, 54% and frontotemporal degeneration, 42%. Detailed characterization of psychosis shows differences in the types of hallucinations and delusions by dementia type. These findings suggest that different types of dementia related pathology are associated with high rates of psychosis with more specific symptom profiles than previously appreciated. Understanding the differences and variety of psychotic experiences across dementia types may have diagnostic and therapeutic implications for treating hallucinations and delusions in populations suffering from neurodegenerative diseases.
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Demencia , Enfermedades Neurodegenerativas , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/psicología , Trastornos Psicóticos/complicaciones , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/psicología , Demencia/epidemiología , Demencia/psicología , Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/psicología , Enfermedad por Cuerpos de Lewy/epidemiología , Deluciones/epidemiología , Deluciones/psicología , Deluciones/etiología , Alucinaciones/epidemiología , Alucinaciones/etiología , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/complicaciones , NeurobiologíaRESUMEN
Novel means are needed to identify individuals and subpopulations susceptible to and afflicted by neurodegenerative diseases (NDDs). This study aimed to utilize geographic distribution of heavy metal sources and sinks to investigate a potential human health risk of developing NDDs. Known or hypothesized environmental factors driving disease prevalence of Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS) are heavy metals, including arsenic (As), cadmium (Cd), manganese (Mn) and mercury (Hg). Lead (Pb) has been associated with AD and ALS. Analyzable mediums of human exposure to heavy metals (i.e., toxic metals and metalloids), or proxies thereof, include infant blood, topsoil, sewage sludge, and well water. U.S. concentrations of heavy metals in topsoil, sewage sludge, well water, and infant blood were mapped and compared to prevalence rates of major NDDs. Data from federal and state agencies (i.e., CDC, EPA, and the US Geological Survey) on heavy metal concentrations, age distribution, and NDD prevalence rates were geographically represented and statistically analyzed to quantify possible correlations. Aside from an expected significant association between NDD prevalence and age (p < 0.0001), we found significant associations between the prevalence of the sum of three major NDDs with: Pb in topsoil (p = 0.0433); Cd (p < 0.0001) and Pb (p < 0.0001) in sewage sludge; Pb in infant blood (p < 0.0001). Concentrations in sewage sludge of Cd and Pb were significantly correlated with NDD prevalence rates with an odds ratio of 2.91 (2.04, 4.225 95%CI) and 4.084 (3.14, 5.312 95%CI), respectively. The presence of toxic metals in the U.S. environment in multiple matrices, including sewage sludge, was found to be significantly associated with NDD prevalence. This is the first use of sewage sludge as an environmental proxy matrix to infer risk of developing NDDs.
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Exposición a Riesgos Ambientales , Metales Pesados , Enfermedades Neurodegenerativas , Metales Pesados/análisis , Humanos , Estados Unidos/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Prevalencia , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/inducido químicamente , Monitoreo del AmbienteRESUMEN
BACKGROUND: Exposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions. OBJECTIVES: To explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases. METHODS: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence. RESULTS: PM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45-2.27; 1.78; 95% CI, 1.37-2.32; and 1.99; 95% CI, 1.54-2.57 for the second, third, and fourth quartiles, respectively). CONCLUSIONS: Long-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals. ENVIRONMENTAL IMPLICATION: PM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.