A large-scale population-based cohort study has revealed a concerning association between primary Sjögren’s syndrome (pSS) and an elevated risk of developing dementia. The research, published in The Korean Journal of Internal Medicine, analyzed data from the Health Insurance Review and Assessment database between 2008 and 2020, providing crucial findings into the long-term neurological risks faced by individuals with pSS.
The study examined 20,160 patients diagnosed with pSS who had no prior history of dementia. A control group, composed of age- and sex-matched individuals without autoimmune disease or dementia, was used for comparison. The results indicated a higher incidence of dementia among pSS patients, with 0.68 cases per 100 person-years, compared to 0.58 cases per 100 person-years in the control group. After adjusting for age, sex, and comorbidities, the hazard ratio (HR) for developing dementia was found to be 1.16 times higher in pSS patients than in controls, highlighting a modest but significant increased risk.
The study also assessed the potential impact of hydroxychloroquine (HCQ) on dementia risk. Patients who initiated HCQ treatment within 180 days of their pSS diagnosis did not exhibit a significantly increased risk of dementia, with an adjusted HR of 1.07. Conversely, those who did not use HCQ had a 1.22 times higher risk of developing dementia compared to the control group. Within the pSS cohort, HCQ users showed a lower dementia risk than non-users, with an adjusted HR of 0.82, suggesting a potential neuroprotective effect of the medication.
Supporting these findings, a systematic review and meta-analysis examined the relationship between systemic rheumatic diseases (SRDs) and dementia. The study analyzed data from 17 observational studies involving 17,717,473 participants. The results demonstrated an increased dementia risk among individuals with osteoarthritis, systemic lupus erythematosus, and Sjögren’s syndrome, with pooled risk ratios (RRs) of 1.31, 1.43, and 1.26, respectively. However, rheumatoid arthritis (RA) did not show a significant association with dementia risk (pooled RR: 0.98). These findings reinforce the need for greater awareness of cognitive impairment in patients with pSS and other SRDs.
The precise mechanisms leading to cognitive impairment and increased dementia risk in pSS patients remain incompletely understood. However, several hypotheses have been proposed. Chronic systemic inflammation characteristic of pSS may extend to the central nervous system, leading to neuronal damage and cognitive deficits. Vascular abnormalities, including small vessel vasculitis, might contribute to subcortical brain lesions observed in some pSS patients, potentially affecting cognitive functions. Additionally, the presence of specific autoantibodies, such as anti-NR2 antibodies, has been linked to cognitive dysfunction in pSS, suggesting a direct autoimmune effect on neuronal tissues. These proposed mechanisms highlight the complex interplay between immune-mediated processes and neurological manifestations in pSS.
These findings underscore the need for increased vigilance regarding cognitive decline in patients with pSS. Early detection of cognitive impairment, along with proactive management strategies, could be essential in reducing the long-term burden of dementia in this vulnerable population. The potential neuroprotective role of HCQ in reducing dementia risk warrants further investigation to establish definitive clinical guidelines. Future research should focus on elucidating the underlying mechanisms linking pSS to dementia and evaluating targeted interventions to improve cognitive outcomes in affected individuals.
References
- Lee KA, Jeon H, Kim HS, Choi K, Seo GH. Increased risk of dementia in patients with primary Sjogren’s syndrome: a nationwide population-based cohort study. Korean J Intern Med. 2025 Feb 21.
- Wang YC, Lin MS, Huang AP, Wu CC, Kung WM. Association between systemic rheumatic diseases and dementia risk: A meta-analysis. Front Immunol. 2022 Nov 9;13:1054246.