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To determine the burden of disease among subjects at risk of developing stroke or dementia, brain health indexes (BHI) tend to rely on anatomical features. Recent definitions emphasize the need of a broader perspective that encompasses cardiovascular risk factors (CVRFS) and lifestyle components which can be considered partial contributors to optimal brain health. In this study, we aimed to establish the association and risk detected by a Brain Health Index and the risk of possible vascular dementia (PVD) using data from the Mexican Health and Aging Study (MHAS) 2012-2015. The MHAS is a longitudinal study of adults aged ≥ 50 years. We analyzed the data obtained between 2012 and 2015. CVRFS included in the index were diabetes mellitus, hypertension, myocardial infarction, depression, obesity, physical inactivity, and smoking history. A PVD diagnosis was established when scores in the Cross-Cultural Cognitive Examination were below reference norms and limitations in ≥1 instrumental activities of daily living and a history of stroke were present. A multinomial regression model was developed to determine the association between BHI scores and PVD. In 2015, 75 PVD cases were identified. Mean age was 67.1 ±13.2 years, 35.8% were female, and the mean educational level was 5.8 ±5.5 years. In cases with a higher score in the BHI, the model revealed a hazards ratio of 1.63 (95% CI: 1.63-1.64, p< 0.001) for PVD. In this longitudinal study, with the use of a feasible multifactorial BHI in the Mexican population, a greater score was associated with a 1.63-fold risk of developing PVD during the 3-year follow-up, while the risk for stroke was 1.75. This index could potentially be used to predict the risk of PVD in adults with modifiable CVRFS.

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Dementia is a syndrome in which there is deterioration in memory, behavior, and the ability to perform everyday activities. Alzheimer's disease and vascular dementia are the most common forms of dementia. There is evidence supporting the hypothesis that inflammatory and immune mechanisms are involved in dementia. Microglia, the resident macrophage tissues in the central nervous system, play a significant role in neuroinflammation and play an important role in amyloid-ß clearance in the brain, and impaired microglial clearance of amyloid-ß has also been shown to be involved in the pathogenesis of Alzheimer's disease. However, there is also abundant evidence that microglia have harmful actions in dementia. Once activated, they can mediate uptake at neuronal synapses. They can also exacerbate tau pathology and secrete deleterious inflammatory factors that can directly or indirectly damage neurons. Thus, depending on the stage of the disease, microglia can act both protectively and detrimentally. Therefore, it is still necessary to continue with studies to better understand the role of microglia in the pathology of dementia. Currently available drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so identifying and studying new therapeutic approaches is important. Considering the role played by microglia in this pathology, it has been pointed out as a possible therapeutic approach. This manuscript aims to address the relationship between microglia and dementia and how this relationship could be used for therapeutic purposes.

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Dementia is a multifactorial disease in which environmental, lifestyle, and genetic factors intervene. Population studies have been used in looking for the susceptibility genes for this disease. Since the activity of dopamine b hydroxylase (DßH) is reduced in the hippocampus and neocortex in the brain, changes in the physiological status of dopamine have been reported in Alzheimer's disease (AD) induced by this enzyme. Therefore, DBH polymorphisms have been associated with susceptibility to some neurological diseases such as AD, but few studies have investigated the relationship between these polymorphisms with other types of dementia, especially in Mexican populations. The aim of this study was to evaluate the association between single-nucleotide polymorphism (SNP) in the dopamine b-hydroxylase (DBH gene (rs1611115) and their interactions with environmental factors and the dementia risk. We examined the genotype of the gene DBH (rs1611115) polymorphism in patients with dementia and healthy. The interaction and the impact of DBH (rs1611115) polymorphism on dementia were examined through multifactor dimensionality reduction (MDR) analysis, and the results were verified by the Chi-square test. Hardy-Weinberg equilibrium (HWE) was also checked by the Chi-square test. The relative risk was expressed by odds ratio (OR) and 95%. A total of 221 dementia patients and 534 controls met the inclusion criteria of MDR analyses. The results of the MDR analysis showed that the development of dementia was positively correlated with interaction between the TT genotype of the DBH1 locus rs1611115 TT and diabetes, hypertension, and alcohol consumption (OR = 6.5: 95% CI = 4.5-9.5), originating further cognitive damage. These findings provide insight into the positive correlation between the metabolism and cardiovascular disorders and the presence of the T allele by means of a recessive model of DBH rs1611115 polymorphism with the suspensibility of dementia.

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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.

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BACKGROUND: Dementia is a priority public health issue due to its high prevalence worldwide and its economic, social, and health impact. However, there are few reports in Mexico based on formal tests and with a clinical approach based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). OBJECTIVE: This study estimates the prevalence of the main types of dementia among elderly people living in the community in Mexico City. METHODS: A population-based, two-step study was conducted, including 6,204 elderly individuals aged 60 or above with in-home assessment. All participants were screened for cognitive impairment; those who presented some cognitive problem underwent a standardized neurological examination. Each diagnosis was based on the criteria for dementia in the DSM-5, and the final consensus diagnosis of dementia was determined by an expert panel. RESULTS: The global estimated prevalence of dementia in the Mexican population was 7.8% met the criteria for Alzheimer's disease, 4.3% for vascular dementia, and 2.1% for mixed dementia. The prevalence of dementia was higher in women than in men (15.3% versus 12.5%, respectively). CONCLUSION: These results provide evidence to propose strategies for Latin American countries where dementia represents a challenge due to the heterogeneity of the populations and socioeconomic disparities, requiring early diagnosis and at the first levels of care.

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Background: Pemphigus vulgaris comprises a group of heterogeneous blistering autoimmune diseases of the skin and mucosa. Esophageal involvement within pemphigus vulgaris is rare with an uncertain prevalence that requires a detailed diagnostic and a therapeutic approach. Clinical case: 37-year-old female, with a history of treatment with Cox-2 inhibitors due to herniated disc. She is sent to the Gastroenterology Service for weight loss of approximately 5 kilos in a month, with the presence of dysphagia, odynophagia and retrosternal pain with poor tolerance to the oral route. Endoscopy was performed, which reported esophagitis dissecans superficialis (EDS), erythematous gastropathy of the antrum and normal duodenum. Findings were correlated with the diagnosis of pemphigus vulgaris with exclusive involvement of the esophagus. The evaluation did not identify lesions on the skin, oral cavity or other mucous membranes. A new endoscopy was performed as a control and it was found immunofluorescence of the esophageal biopsy reactive to IgG 2. Initial management was given with glucocorticoids, anti-inflammatories and immunosuppressants. Conclusions: The importance of the study of pemphigus lies not only in the high associated morbidity and mortality, but also in its intrinsic rarity and the complexity of its detection, given that patients usually take several months to have an accurate diagnosis and even more time to achieve therapeutic goals. It is a priority the dissemination of the study of pemphigus among health professionals involved in its detection.

Introducción: el pénfigo vulgar comprende un grupo de enfermedades heterogéneas autoinmunes ampollosas de la piel y las mucosas. La afectación esofágica en el pénfigo vulgar es rara, con una prevalencia incierta que requiere un abordaje diagnóstico y terapéutico detallado. Caso clínico: mujer de 37 años, con antecedentes de tratamiento con inhibidores de la Cox-2 debido a hernia discal. Se envió a Gastroenterología por pérdida de peso de aprox. 5 kg en un mes. La paciente tuvo presencia de disfagia, odinofagia y dolor retroesternal con pobre tolerancia a la vía oral. Se hizo endoscopía que reportó esofagitis disecante superficial y gastropatía eritematosa de antro; el duodeno estaba en estado normal. Los hallazgos se correlacionaron con el diagnóstico de pénfigo vulgar con afectación exclusiva a esófago. En la valoración no se identificaron lesiones en piel, cavidad oral u otras mucosas. Se hizo nueva endoscopía como control y se encontró inmunofluorescencia de biopsia esofágica reactiva a IgG 2. Se dio manejo inicial con glucocorticoides, antiinflamatorios e inmunosupresores. Conclusiones: la importancia del estudio del pénfigo radica no solo en la alta morbimortalidad asociada, sino en lo raro y complejo de su detección, pues los pacientes suelen tardar varios meses en tener un diagnóstico certero y aún más en conseguir las metas terapéuticas. Es prioritaria la difusión del estudio del pénfigo entre los profesionales de la salud involucrados en su detección.

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BACKGROUND: The pathogenesis of mild cognitive impairment (MCI) is multifactorial and includes the presence of genetic variants such as the ε4 allele of the apolipoprotein E gene (APOE-ε4). Association between the APOE-ε4 carrier status and deleterious structural and functional changes on magnetic resonance imaging (MRI) has been previously described in individuals with Alzheimer's disease. However, the central nervous system changes may possibly develop in earlier stages of cognitive impairment, as reflected in MCI. OBJECTIVE: The objective of the study was to determine the association between APOE-ε4 carrier status and qualitative changes on MRI (medial temporal and parietal atrophy), as well as the detection of white matter hyperintensities (WMH) in older adults with MCI, in the memory clinic of a tertiary care hospital in Mexico City. METHODS: A cross-sectional study of 72 adults aged 60 years or above who underwent an exhaustive clinical, neuroimaging, and neuropsychological evaluation. Multivariate logistic regression models were constructed to determine the association between APOE-ε4 carrier status and qualitative/quantitative changes on MRI. RESULTS: Mean age was 75.2 years (± 7.2) and 64% were female. Twenty-one participants were cognitively normal and 51 had MCI. Almost 56% were APOE-ε4 carriers and were associated with medial-temporal atrophy according to the Scheltens scale (odds ratio [OR]: 20.0, 95% confidence intervals [CI]: 3.03-131.7), parietal atrophy according to the Koedam's score (OR: 6.3; 95% CI 1.03-39.53), and WMH according to the Fazekas scale (OR: 11.7, 95% CI: 1.26-108.2), even after adjusting for age, educational level, and cardiovascular risk factors. CONCLUSION: The APOE-ε4 carrier status was associated with medial temporal and parietal atrophy, as well as WMH. Our findings support the hypothesis suggesting the contribution of this genotype to neurodegeneration and cerebral vascular pathology.

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Introducción: el pénfigo vulgar comprende un grupo de enfermedades heterogéneas autoinmunes ampollosas de la piel y las mucosas. La afectación esofágica en el pénfigo vulgar es rara, con una prevalencia incierta que requiere un abordaje diagnóstico y terapéutico detallado. Caso clínico: mujer de 37 años, con antecedentes de tratamiento con inhibidores de la Cox-2 debido a hernia discal. Se envió a Gastroenterología por pérdida de peso de aprox. 5kg en un mes. La paciente tuvo presencia de disfagia, odinofagia y dolor retroesternal con pobre tolerancia a la vía oral. Se hizo endoscopía que reportó esofagitis disecante superficial y gastropatía eritematosa de antro; el duodeno estaba en estado normal. Los hallazgos se correlacionaron con el diagnóstico de pénfigo vulgar con afectación exclusiva a esófago. En la valoración no se identificaron lesiones en piel, cavidad oral u otras mucosas. Se hizo nueva endoscopía como control y se encontró inmunofluorescencia de biopsia esofágica reactiva a IgG 2. Se dio manejo inicial con glucocorticoides, antiinflamatorios e inmunosupresores. Conclusiones: la importancia del estudio del pénfigo radica no solo en la alta morbimortalidad asociada, sino en lo raro y complejo de su detección, pues los pacientes suelen tardar varios meses en tener un diagnóstico certero y aún más en conseguir las metas terapéuticas. Es prioritaria la difusión del estudio del pénfigo entre los profesionales de lasalud involucrados en su detección.

Background: Pemphigus vulgaris comprises a group of heterogeneous blistering autoimmune diseases of the skin and mucosa. Esophageal involvement within pemphigus vulgaris is rare with an uncertain prevalence that requires a detailed diagnostic and a therapeutic approach. Clinical case: 37-year-old female, with a history of treatment with Cox-2 inhibitors due to herniated disc. She is sent to the Gastroenterology Service for weight loss of approximately 5 kilos in a month, with the presence of dysphagia, odynophagia and retrosternal pain with poor toleranceto the oral route. Endoscopy was performed, which reported esophagitis dissecans superficialis (EDS), erythematous gastropathy of the antrum and normal duodenum. Findings were correlated with the diagnosis ofpemphigus vulgaris with exclusive involvement of the esophagus. The evaluation did not identify lesions on the skin, oral cavity or other mucous membranes. A new endoscopy was performed as a control and it was found immunofluorescence of the esophageal biopsy reactive to IgG 2. Initial management was given with glucocorticoids, anti-inflammatories and immunosuppressants. Conclusions: The importance of the study ofpemphigus lies not only in the high associated morbidity and mortality, but also in its intrinsic rarity and the complexity of its detection, given that patients usually take several months to have an accurate diagnosis and even more time to achieve therapeutic goals. It is a priority the dissemination of the study of pemphigus among health professionals involved in its detection.

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There is an inconsistent finding about the relationship of catechol-O-methyltransferase (COMT) with dementia susceptibility, as well as with cognitive impairment. To substantiate this, we examined COMT genotype effects in certain cognitive domains in dementia. To evaluate the effects of COMT Val158Met on cognitive performance, we used The Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) and the Syndrome Kurz Test (SKT). The results show COMT Val/Met, Val/Val genotype polymorphisms had a significant effect on cognition performance (OR = 1.75 (95 %CI 1.22-2.54) and (OR = 2.76 (95 %CI 1.78-4.26), p < 0.001), and with adjustment for all cognitive test scores together, Val/Val (OR = 4.98 (95 % CI 1.47-16.86) and Val/Met (OR = 3.62 (95 % CI 1.37-9.56) had effect. Our study allows us to understand the role of COMT in cognitive performance in dementia, as well as interaction with other known risk factors for this pathology. This data might help in developing new therapeutic targets for cognitive impairment, main symptom of dementia. Other risk genotypes or haplotypes should be evaluated to determine the association with cognitive decline in dementia.

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Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer's disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

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One of the hypotheses that have emerged to explain the origin of dementia relates the disease with altered lipid metabolism, particularly cholesterol. To maintain cholesterol homeostasis, the ACAT1 enzyme has an important function to regulate the production of Aß. Moreover, APOE is the main cholesterol carrier in the brain, and it has been reported as a risk factor for this disease. This study evaluates the relationship between ACAT1 and APOE genetic variants with susceptibility for the development of Alzheimer's disease and other dementias. We examined four ACAT1 polymorphisms (rs2247071, rs2862616, rs3753526, rs1044925) and two in the APOE gene (rs7412, rs429358) in a group of 204 controls and 196 cases of dementia. Our results show one protective haplotype: CGCA (OR = 0.34, 95% CI = 0.23-0.46; p < 0.001) and one risk haplotype: CGGA (OR = 1.87, 95% CI = 1.34-2.60; p < 0.001) for the development of dementia. Subjects identified as APOE-ε4 allele carriers had a higher risk of developing dementia compared with non-carriers, OR = 13.33 (95% CI = 3.14-56.31). The results support the hypothesis that the ACAT1 gene, together with the APOE gene, plays an important role in susceptibility to the development of dementia and shows genetic characteristics of the Mexican population that can be used to identify the population at risk.

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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.

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Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5' exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student's t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047; OR = 0.59, pCDominant = 0.014; OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028; OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population.

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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.

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Background: Frailty, a state of increased vulnerability, could play a role in the progression of vascular dementia. We aim to describe the changes in cerebrovascular reactivity of older adults with frailty and vascular-type mild cognitive impairment (MCIv). Methods: This was a cross-sectional study. A comprehensive geriatric assessment, neuropsychological evaluation, and transcranial Doppler ultrasound (TCD) was performed on 180 participants who were allocated into four groups: healthy (n = 74), frail (n = 40), MCIv (n = 35), and mixed (frail + MCIv) (n = 31). ANOVA and Kruskal-Wallis tests were used for the analysis of continuous variables with and without normal distribution. Multinomial logistic regression was constructed to identify associated covariates. Results: Subjects in the mixed group, compared to healthy group, were older (75.0 ± 5.9 vs 70.3 ± 5.9 years; p < 0.001), showed lower education (9.3 ± 6.4 vs 12.2 ± 4.0 years; p = 0.054), greater frequency of diabetes (42% vs 12%; p = 0.005), worse cognitive performance (z = -0.81 ± 0.94), and reduced left medial-cerebral artery cerebrovascular reactivity (0.43 ± 0.42 cm/s). The mixed group was associated with age (odds ratio (OR) 1.16, 95% Confidence Interval (CI) = 1.06-1.27; p < 0.001), diabetes (OR 6.28, 1.81-21.84; p = 0.004), and Geriatric Depression Scale (GDS) score (OR 1.34, 95% CI = 1.09-1.67; p = 0.007). Conclusions: Frailty among older adults was associated with worse cognitive performance, diabetes, and decreased cerebral blood flow.

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BACKGROUND: Alzheimer´s disease (AD) is a chronic and progressive disease which impacts caregivers, families and societies physically, psychologically and economically. Currently available drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so identifying and studying new drug targets is important. There are evidences which indicate disturbances in cholesterol homeostasis can be related with AD pathology, especially the compartmentation of intracellular cholesterol and cytoplasmic cholesterol esters formed by acyl-CoA: cholesterol acyltransferase 1 (ACAT1) can be implicated in the regulation of amyloid-beta (Aß) peptide, involved in AD. Blocking ACAT1 activity, beneficial effects are obtained, so it has been suggested that ACAT1 can be a potential new therapeutic target. The present review discusses the role of cholesterol homeostasis in AD pathology, especially with ACAT inhibitors, and how they have been raised as a therapeutic approach. In addition, the genetic relationship of ACAT and AD is discussed. CONCLUSION: Although there are several lines of evidence from cell-based and animal studies that suggest that ACAT inhibition is an effective way of reducing cerebral Aß, there is still an information gap in terms of mechanisms and concerns to cover before passing to the next level. Additionally, an area of interest that may be useful in understanding AD to subsequently propose new therapeutic approaches is pharmacogenetics; however, there is still a lot of missing information in this area.

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BACKGROUND: Mild cognitive impairment (MCI) is considered a clinical stage between normal cognitive aging and dementia. The clinical course of MCI is heterogeneous, with a significant number of cases progressing to dementia or reverting back to normal. OBJECTIVE: To determine the predictors of conversion from mild cognitive impairment to dementia among Mexican older adults. MATERIALS AND METHODS: A sample of 175 persons underwent clinical and neuropsychological evaluation to establish mild cognitive impairment diagnosis. These patients were followed-up for a mean 3.5 years. RESULTS: Mean age was 81.7 (± 6.9) years, 57% were women, and mean education level was 9.5 (± 6.1) years. Sixty-one percent of mild cognitive impairment participants progressed to dementia. Multivariate Cox regression analysis showed that progression to dementia was associated with age (HR: 4.95; 95% CI: 1.96-12.46; p = 0.001), low education level (HR: 5.81; 95% CI: 1.90-7.78; p < 0.002), history of stroke (HR: 3.92; 95% CI: 1.37-11.16; p < 0.012) and cognitive decline (HR: 1.31; 95% CI: 1.18-1.45; p = 0.000). CONCLUSIONS: Age, poor education, cognitive decline, and a history of stroke were predictors of conversion to dementia. The identification and control of modifiable risk factors could influence conversion to dementia.

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Aging is considered a systemic, chronic and low-grade inflammatory state, called "inflammaging", which has been contemplated as a risk factor for cancer development and progression in the elderly population. Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as a contributor to aging. Senescent cells have an altered secretion pattern called Senescent Associated Secretory Phenotype (SASP), that comprise a complex mix of factors including cytokines, growth factors, chemokines and matrix metalloproteinases among others. The SASP secreted by accumulated senescent cells during old age has been related to local inflammation that leads to cellular transformation and therefore may be supporting the inflammaging process. Here, we evaluated if the pro-inflammatory profile within the serum obtained from elderly patients (EPS) was able to induce cellular proliferation in the breast cancer transformed cell line (MCF-7), in a similar way to the proliferation stimulated by the SASP obtained from WI-38 primary cells prematurely induced to senescence by oxidative stress (SIPS). At the same time, the participation of IL-6/IL-8 ratio was determined. Our results showed that not all the EPS increased MCF-7 proliferation. However, there was an interesting relationship between IL-6 and IL-8 concentrations, when the IL-6 was higher than IL-8. Similar results were found with SASP from SIPS-WI-38 on the MCF-7 proliferation. Although it is known that those cytokines are fundamental factors to induce proliferation; the occurrence of other components in the cellular microenvironment is necessary to carry out this effect.

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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.

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OBJECTIVE: To identify the main severe potential drug-drug interactions in older adults with dementia and to examine the factors associated with these interactions. METHOD: This was a cross-sectional study. The enrolled patients were selected from six geriatrics clinics of tertiary care hospitals across Mexico City. The patients had received a clinical diagnosis of dementia based on the current standards and were further divided into the following two groups: those with severe drug-drug interactions (contraindicated/severe) (n=64) and those with non-severe drug-drug interactions (moderate/minor/absent) (n=117). Additional socio-demographic, clinical and caregiver data were included. Potential drug-drug interactions were identified using Micromedex Drug Reax 2.0® database. RESULTS: A total of 181 patients were enrolled, including 57 men (31.5%) and 124 women (68.5%) with a mean age of 80.11±8.28 years. One hundred and seven (59.1%) patients in our population had potential drug-drug interactions, of which 64 (59.81%) were severe/contraindicated. The main severe potential drug-drug interactions were caused by the combinations citalopram/anti-platelet (11.6%), clopidogrel/omeprazole (6.1%), and clopidogrel/aspirin (5.5%). Depression, the use of a higher number of medications, dementia severity and caregiver burden were the most significant factors associated with severe potential drug-drug interactions. CONCLUSIONS: Older people with dementia experience many severe potential drug-drug interactions. Anti-depressants, antiplatelets, anti-psychotics and omeprazole were the drugs most commonly involved in these interactions. Despite their frequent use, anti-dementia drugs were not involved in severe potential drug-drug interactions. The number and type of medications taken, dementia severity and depression in patients in addition to caregiver burden should be considered to avoid possible drug interactions in this population.

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