Synergistic influence of cytokine gene polymorphisms over the risk of dementia: A multifactor dimensionality reduction analysis.

Objective: Evidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ) on the susceptibility to the development of dementia. Materials and methods: In the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-α (rs1800587), IL-6 (rs1800796), TNFα (rs361525 and rs1800629), and IFNγ (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency. Results: Multifactor-dimensionality reduction analysis detected a significant model with the genes TNFα, IFNγ, IL1α, and IL6 (prediction success: 72%, p < 0.0001). When risk factors were analyzed with these polymorphisms, the model achieved a similar prediction for dementia as the genes-only model. Conclusion: These data indicate that gene-gene interactions form significant models to identify populations susceptible to dementia.

Randomized Controlled Trial of Multi-Component Cognitive Stimulation Therapy (SADEM) in Community-Dwelling Demented Adults.

BACKGROUND: Dementia is a persistent, progressive state of cognitive decline against which pharmacological intervention has a modest efficacy, reducing behavioral but not cognitive symptoms. Therefore, different non-pharmacological therapies have been developed; the most scientifically recognized are cognitive therapies that have improved cognitive function and daily life activities. OBJECTIVE: To evaluate the effectiveness of a multicomponent cognitive stimulation therapy (SADEM) on cognitive and behavioral function and daily life activities in patients with mild stage dementia. METHODS: Controlled clinical trial with pre- and post-intervention (12 months) and follow-up (24 months after) evaluations. Participants (67) diagnosed with mild dementia were randomly assigned to intervention group (n = 39) or control group (n = 28). The intervention took place throughout one year and consisted of two weekly 90-minute sessions and one more a year after a monthly follow-up. Instruments were used to evaluate outcomes in cognitive, behavioral, and affective domains. RESULTS: The results showed statistically significant differences, with improvement in the cognitive outcomes and the Dementia Index post-intervention (p = 0.01). No progression of the disease was observed at the end of the study. CONCLUSION: The multicomponent intervention tested had positive effects on cognitive and behavioral functions and daily life activities in people with mild stage dementia, delaying progression for at least two years.

Interleukin 10 gene polymorphisms and frailty syndrome in elderly Mexican people: (Sadem study).

Frailty is a geriatric syndrome, characterized by a loss in functional reserve with an increase in morbidity and mortality. There are no reports that link the genetic polymorphisms between interleukin 10 (IL10) and frailty; for this reason, our objective was used to analyze the role of the polymorphisms of IL10 (rs1800896, rs1800871) in the susceptibility to frailty in a Mexican population. Our study included 984 participants divided into 368 nonfrail, 309 prefrail, and 307 frail. The models for the polymorphisms rs1800896 and rs1800871 were recessive models in association with frailty (OR = 2.3, CI 95% = 1.6-3.2; OR = 1.53, CI 95% = 1.0-2.6), respectively. Two risk haplotypes were identified: ACG and CCG (p < .0001), and three protective haplotypes were identified: ACA, ATG, and ATA (p < .05). This study evaluated the relationship between IL10 and the three subtypes of this geriatric syndrome (frail, prefrail, and nonfrail). These results support a greater susceptibility to frailty for the minor alleles of rs1800871 and rs1800896. In addition, we found two risk haplotypes supporting the participation of the IL10 in the susceptibility for frailty in the Mexican population.

Association of interleukin-10 polymorphisms with risk factors of Alzheimer's disease and other dementias (SADEM study).

Some studies have reported a genetic association between single nucleotide polymorphisms (SNPs) in the promoter region of Interleukin (IL) 10 and Alzheimer's disease (AD), with conflicting results. To further investigate the proposed association and to clarify the role of cytokines as a potential cause for AD susceptibility, we analyzed genotypes, allele distributions and haplotypes of IL-10 promoter polymorphisms -1082 (rs1800896) and -819 (rs1800871) in a Mexican population: 986 normal controls and 221 cases divided as follows: 122 with Alzheimer disease (AD), 67 with (VaD) and 32 with mixed dementia (AD/VaD). Patients with dementia showed increased frequency of "ATA, CTG, and CTA" haplotypes when compared to controls. We identified two risk haplotypes: ATA (OR=3.56, 95%CI=2.84-4.45, p<0.0001), and CTA (OR=1.90, 95%CI=1.38-2.62, p<0.0001), and four protection haplotypes: ATG (OR=0.60, 95%CI=0.45-0.82, p=0.0012), CTG (OR=0.38, 95%CI=0.23-0.62, p<0.0001), ACG (OR=0.01, 95%CI=0.002-1.13, p<0.0001), and CCG (OR=0.02, 95%CI=0.004-0.203, p<0.0001). In summary, this is the first study in Mexican population that considers the analysis of IL-10 in patients with AD, VaD and AD/VaD. Our results showed the relevance of the role that IL-10 plays in the pathological mechanisms that result in the development of dementia. In addition, in our study, it was possible to distinguish two protective and two risk haplotypes for the development of dementia.