Multimorbidity (the presence of two or more long-term conditions [LTCs]) was suggested to exacerbate the neuronal injuries. The impact of multimorbidity on dementia has not been fully elucidated. We aimed to investigate the association between multimorbidity and dementia risk. We used the prospective data from 245,483 UK Biobank participants during a 9-year follow-up. Multimorbidity status was evaluated based on the LTC counts and multimorbidity patterns. Cox regression models adjusted for potential confounders were used to examine the associations of multimorbidity status with all-cause dementia (ACD), Alzheimer’s disease (AD) and vascular dementia (VD). Participants with multimorbidity at baseline had higher risks of ACD and VD, and the risks were elevated with the increase of LTC counts (ACD: hazard ratios [HR] = 1.15, 95% confidence intervals [CI] = 1.01–1.31 with 2 LTCs; HR = 1.18, CI = 1.01–1.39 with 3 LTCs; HR = 1.65, CI = 1.44–1.88 with ≥4 LTCs; VD: HR = 1. 66, CI = 1.24–2.21 with 2 LTCs; HR = 2.10, CI = 1.53–2.88 with 3 LTCs; HR = 3.17, CI = 2.43–4.13 with ≥4 LTCs). Participants with ≥4 LTCs also had a higher risk of AD (HR = 1.34, CI = 1.08–1.66]. Participants with the cardio-cerebrovascular/respiratory/metabolic/musculoskeletal/depressive multimorbidity were 1.46, 1.28, and 2.50 times more likely to develop ACD (HR = 1.46, 95% CI = 1.28–1.67), AD (HR = 1.28, CI = 1.04–1.58), and VD (HR = 2.50, CI = 1.90–3.27), respectively. Those with tumor/genitourinary/digestive disorders had a 11% higher hazard of ACD (HR = 1.11, CI = 1.00–1.24) and a 73% elevated risk of VD (HR = 1.73, CI = 1.37–2.18). The prevention of LTC accumulation and the identification of specific multimorbidity patterns might be beneficial to the prevention of dementia and its subtypes, AD as well as VD.

Background: Excessive oxidative stress may contribute to neurodegeneration by leading to protein aggregation and mitochondrial dysfunction. Uric acid (UA) is an important endogenous antioxidant that protects against oxidative stress, yet its exact role in neurodegeneration remains unclear. Objective: To explore the performance of serum UA in neurodegenerative disorders. Methods: A total of 839 controls and 840 patients, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), motor neuron disease (MND), Creutzfeldt-Jakob disease (CJD), and mixed dementia (MixD) were enrolled. Fasting serum UA levels were measured in all participants and compared between patients and controls. Linear regression models were utilized to explore possible relationships of serum UA with cognition, disease duration, age, and age of onset. Results: Compared to controls (355.48 ± 85.38 μmol/L), serum UA was significantly lower in AD (291.29 ± 83.49 μmol/L, p < 0.001), PD (286.95 ± 81.78 μmol/L, p < 0.001), PSP (313.32 ± 88.19 μmol/L, p < 0.001), FTD (313.89 ± 71.18 μmol/L, p = 0.001), and DLB (279.23 ± 65.51 μmol/L, p < 0.001), adjusting for confounding factors including age, gender, education, etc. In addition, serum UA was positively correlated with cognitive levels in all patients (Mini-Mental State Examination: r = 0.136, p = 0.001; and Montreal Cognitive Assessment Scale: r = 0.108, p = 0.009). Conclusion: Decreased levels of serum UA were correlated with AD, PD, PSP, FTD, and DLB, offering significant potential as a promisingly relevant, less-invasive marker of multiple neurodegenerative disorders.