Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals
Abstract Background Immune system dysregulation plays a vital role in the pathogenesis of neurodegenerative diseases, even considered to be as important as classical pathological protein aggregation assumption. However, the associations of immune-mediated diseases with incident dementia are unclear...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-09-01
|
| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-022-01072-x |
| _version_ | 1797995008468451328 |
|---|---|
| author | Ya-Ru Zhang Liu Yang Hui-Fu Wang Bang-Sheng Wu Shu-Yi Huang Wei Cheng Jian-Feng Feng Jin-Tai Yu |
| author_facet | Ya-Ru Zhang Liu Yang Hui-Fu Wang Bang-Sheng Wu Shu-Yi Huang Wei Cheng Jian-Feng Feng Jin-Tai Yu |
| author_sort | Ya-Ru Zhang |
| collection | DOAJ |
| description | Abstract Background Immune system dysregulation plays a vital role in the pathogenesis of neurodegenerative diseases, even considered to be as important as classical pathological protein aggregation assumption. However, the associations of immune-mediated diseases with incident dementia are unclear and need to be clarified in prospective studies with a large population and long follow-up time. Methods We investigated the relationship between any or individual immune-mediated diseases and incident dementia based on a prospective cohort UK Biobank. The risk for dementia was assessed with multivariable hazard ratio (HR) and 95% confidence interval (CI) after adjusting for various potential confounders using time-varying Cox proportional hazards regression. We also performed the subgroup Cox analysis stratified by time since immune-mediated diseases and gender. Causal mediation analyses with 1000 bootstrapped iterations were conducted to explore the mediation effects of peripheral immune cells on the associations of immune-mediated diseases with dementia. Results A total of 375,894 participants were included in the study, among which 5291 developed dementia during a median follow-up of 9.08 years. Immune-mediated diseases were associated with an increased risk of dementia (HR, 1.10; 95% CI, 1.00–1.21), and the risk was highest between 1 and 2 years after immune-mediated diseases onset (HR, 2.74; 95% CI, 1.86–4.04). Females who suffered from immune-mediated diseases were more prone to AD, while males were more susceptible to VD. Four of the individual immune-mediated diseases including type I diabetes mellitus (HR, 2.49; 95% CI, 1.97–3.15), rheumatic fever or rheumatic heart diseases (HR, 1.36; 95% CI, 1.05–1.77), multiple sclerosis (HR, 2.87; 95% CI, 1.92–4.30), and necrotizing vasculopathies (HR, 1.71; 95%CI, 1.03–2.85) were significantly related to higher dementia incidence. The relationship between immune-mediated diseases and dementia was partially mediated by peripheral immune cells including neutrophils and lymphocytes. Conclusions In this large cohort study, immune-mediated diseases were proven to be significantly associated with an increased risk of incident dementia, especially for type I diabetes mellitus which was observed to be related to the higher incidence of all types of dementia. Our findings could provide new sights on dementia pathogenesis and intervention from the perspective of systemic immunology and immune-mediated diseases. |
| first_indexed | 2024-04-11T09:53:37Z |
| format | Article |
| id | doaj.art-05f187f11b9546469afddf532a5cdb8a |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-04-11T09:53:37Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-05f187f11b9546469afddf532a5cdb8a2022-12-22T04:30:41ZengBMCAlzheimer’s Research & Therapy1758-91932022-09-0114111010.1186/s13195-022-01072-xImmune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individualsYa-Ru Zhang0Liu Yang1Hui-Fu Wang2Bang-Sheng Wu3Shu-Yi Huang4Wei Cheng5Jian-Feng Feng6Jin-Tai Yu7Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological DisordersDepartment of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological DisordersDepartment of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological DisordersDepartment of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological DisordersDepartment of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological DisordersInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityDepartment of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological DisordersAbstract Background Immune system dysregulation plays a vital role in the pathogenesis of neurodegenerative diseases, even considered to be as important as classical pathological protein aggregation assumption. However, the associations of immune-mediated diseases with incident dementia are unclear and need to be clarified in prospective studies with a large population and long follow-up time. Methods We investigated the relationship between any or individual immune-mediated diseases and incident dementia based on a prospective cohort UK Biobank. The risk for dementia was assessed with multivariable hazard ratio (HR) and 95% confidence interval (CI) after adjusting for various potential confounders using time-varying Cox proportional hazards regression. We also performed the subgroup Cox analysis stratified by time since immune-mediated diseases and gender. Causal mediation analyses with 1000 bootstrapped iterations were conducted to explore the mediation effects of peripheral immune cells on the associations of immune-mediated diseases with dementia. Results A total of 375,894 participants were included in the study, among which 5291 developed dementia during a median follow-up of 9.08 years. Immune-mediated diseases were associated with an increased risk of dementia (HR, 1.10; 95% CI, 1.00–1.21), and the risk was highest between 1 and 2 years after immune-mediated diseases onset (HR, 2.74; 95% CI, 1.86–4.04). Females who suffered from immune-mediated diseases were more prone to AD, while males were more susceptible to VD. Four of the individual immune-mediated diseases including type I diabetes mellitus (HR, 2.49; 95% CI, 1.97–3.15), rheumatic fever or rheumatic heart diseases (HR, 1.36; 95% CI, 1.05–1.77), multiple sclerosis (HR, 2.87; 95% CI, 1.92–4.30), and necrotizing vasculopathies (HR, 1.71; 95%CI, 1.03–2.85) were significantly related to higher dementia incidence. The relationship between immune-mediated diseases and dementia was partially mediated by peripheral immune cells including neutrophils and lymphocytes. Conclusions In this large cohort study, immune-mediated diseases were proven to be significantly associated with an increased risk of incident dementia, especially for type I diabetes mellitus which was observed to be related to the higher incidence of all types of dementia. Our findings could provide new sights on dementia pathogenesis and intervention from the perspective of systemic immunology and immune-mediated diseases.https://doi.org/10.1186/s13195-022-01072-xDementiaAlzheimer’s diseaseImmune-mediated diseasesNeutrophilsLymphocytes |
| spellingShingle | Ya-Ru Zhang Liu Yang Hui-Fu Wang Bang-Sheng Wu Shu-Yi Huang Wei Cheng Jian-Feng Feng Jin-Tai Yu Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals Alzheimer’s Research & Therapy Dementia Alzheimer’s disease Immune-mediated diseases Neutrophils Lymphocytes |
| title | Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals |
| title_full | Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals |
| title_fullStr | Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals |
| title_full_unstemmed | Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals |
| title_short | Immune-mediated diseases are associated with a higher incidence of dementia: a prospective cohort study of 375,894 individuals |
| title_sort | immune mediated diseases are associated with a higher incidence of dementia a prospective cohort study of 375 894 individuals |
| topic | Dementia Alzheimer’s disease Immune-mediated diseases Neutrophils Lymphocytes |
| url | https://doi.org/10.1186/s13195-022-01072-x |
| work_keys_str_mv | AT yaruzhang immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT liuyang immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT huifuwang immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT bangshengwu immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT shuyihuang immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT weicheng immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT jianfengfeng immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals AT jintaiyu immunemediateddiseasesareassociatedwithahigherincidenceofdementiaaprospectivecohortstudyof375894individuals |