Role of Nitric oxide synthase II in cognitive impairment due to experimental cerebral malaria.

The role of nitric oxide (NO) in the pathogenesis of cerebral malaria and its cognitive sequelae remains controversial. Cerebral malaria is still the worst complication of Plasmodium falciparum infection, which is characterized by high rates of morbidity and mortality. Even after recovery from infection due to antimalarial therapy, the development of cognitive impairment in survivors reinforces the need to seek new therapies that demonstrate efficacy in preventing long-lasting sequelae. During disease pathogenesis, reactive oxygen and nitrogen species (RONS) are produced after the established intense inflammatory response. Increased expression of the enzyme inducible nitric oxide synthase (iNOS) seems to contribute to tissue injury and the onset of neurological damage. Elevated levels of NO developed by iNOS can induce the production of highly harmful nitrogen-reactive intermediates such as peroxynitrite. To address this, we performed biochemical and behavioral studies in C57BL6 mice, aminoguanidine (specific pharmacological inhibitor of the enzyme iNOS) treated and iNOS-/-, infected with Plasmodium berghei ANKA (PbA), with the aim of clarifying the impact of iNOS on the pathogenesis of cerebral malaria. Our findings underscore the effectiveness of both strategies in reducing cerebral malaria and providing protection against the cognitive impairment associated with the disease. Here, the absence or blockade of the iNOS enzyme was effective in reducing the signs of cerebral malaria detected after six days of infection. This was accompanied by a decrease in the production of pro-inflammatory cytokines and reactive oxygen and nitrogen species. In addition, nitrotyrosine (NT-3), a marker of nitrosative stress, was also reduced. Futher, cognitive dysfunction was analyzed fifteen days after infection in animals rescued from infection by chloroquine treatment (25 mg/kg bw). We observed that both interventions on the iNOS enzyme were able to improve memory and learning loss in mice. In summary, our data suggest that the iNOS enzyme has the potential to serve as a therapeutic target to prevent cognitive sequelae of cerebral malaria.

Optimal cutoff scores of the Montreal Cognitive Assessment to detect mild cognitive impairment and dementia in Costa Rican older adults.

BACKGROUND: The burden of Alzheimer's disease and related dementias (AD/ADRD) in Costa Rica is expected to become one of the highest in the region. Early detection will help optimize resources and improve primary care interventions. The Montreal Cognitive Assessment (MoCA) has shown good sensitivity for detecting mild cognitive impairment (MCI), but specificity varies depending on the population. This motivated the analysis of different cutoffs to minimize false-positive classifications in a Costa Rican sample for its use in clinical settings. METHODS: Data was analyzed from 516 memory clinic outpatients (148 cognitively normal, 260 MCI, 108 mild AD/ADRD; mean age 66.3 ± 10.8 years) who underwent complete neurological and neuropsychological assessment and were diagnosed by consensus. Optimal MoCA cutoff scores were identified using a multiple cutoff approach. RESULTS: Overall, a cutoff score of ≥ 23 showed better accuracy to distinguish between normal cognition (NC) and MCI (sensitivity 73%, specificity 83%). When analyzed by educational levels, a cutoff score of ≥ 21 showed better accuracy for ≤ 6 years (sensitivity 80%, specificity 76%), ≥23 for 7-12 years (sensitivity 86%, specificity 76%) and ≥ 24 for > 12 years (sensitivity 70%, specificity 85%). For distinguishing MCI from mild AD/ADRD, the optimal overall cutoff score was ≥ 15 (sensitivity 66%, specificity 85%). When stratified by years of education, cutoff scores of ≥ 14 showed better accuracy for ≤ 6 years (sensitivity 70%, specificity 88%), ≥15 for 7-12 years (sensitivity 46%, specificity 95%) and ≥ 17 for > 12 years (sensitivity 67%, specificity 93%). CONCLUSIONS: A MoCA cutoff score of ≥ 23 in the Costa Rican population showed better diagnostic accuracy for detecting MCI and may reduce the false positive rate. Our findings may be helpful for primary care clinical settings and further referral criteria.

Circulating Cell-Free Mitochondrial DNA in Plasma of Individuals with Schizophrenia and Cognitive Deficit in Mexican Population.

Purpose: Cognitive domains are affected in patients with schizophrenia. Mitochondrial dysfunction has been proposed as a possible origin of these symptoms. Cell-free mitochondrial DNA (cf-mtDNA) is an indicator of cellular stress, and it can be identified in individuals with age-associated disorders, this study aimed to explore the presence of cf-mtDNA in plasma of schizophrenia patients and its association with cognitive deficit. Patients and Methods: Ninety-nine subjects were clinically evaluated; the case group included 60 patients diagnosed with schizophrenia and 39 randomly-individuals without psychiatric disorders were included in the comparison group. Cognitive status (MoCA scale) and cell-free mtDNA in blood plasma were assessed and quantified in both groups. Results: From the original sample, cf-mtDNA was identified in 43 subjects, 40 patients with schizophrenia and 3 controls (Χ2 = 31.10, p-value < 0.0001). Thirty-nine out of forty patients with schizophrenia had a cognitive deficit. Conclusion: According to our findings, cognitive impairment and presence of cf-mtDNA were related in subjects with schizophrenia. Thus, while the cognitive deficit might reflect an accelerated aging process, the cf-mtDNA plays a role as a potential biomarker in this mechanism.

Prevalence of cancer-related cognitive impairment among patients with nasopharyngeal carcinoma: a cross-sectional study.

OBJECTIVE: To examine the prevalence of cancer-related cognitive impairment (CRCI) and its contributing factors in patients with nasopharyngeal carcinoma (NPC) and explore the relationship between various assessment methods. METHODS: A cross-sectional study was conducted with 367 patients with NPC between March 2022 and April 2024 at Chongqing University Cancer Hospital. The data gathered from the demographic questionnaire, Montreal Cognitive Assessment (MoCA), Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were analyzed using logistic regression. RESULTS: Out of 367 participants, males accounted for 271 (73.84%). There were 217 (59.13%) individuals aged between 35-55 years. Cognitive impairment incidence was 58.04% using MoCA and 47.98% using FACT-Cog. Years of education, work condition, age and time since diagnosis (≥ 11 months) were all significantly associated with cognitive impairment using MoCA, the strongest being time since diagnosis (≥ 11 months) (OR = 2.672, 95% CI = 1.191-5.997, P = 0.017). Gender, marital status (married), place of residence (township), place of residence (city), alcohol history, SAS and SDS were all significantly associated with FACT-Cog, the strongest being marital status (married) (OR = 4.100, 95% CI = 1.130-14.87, P = 0.032). CONCLUSION: Patients diagnosed with NPC exhibit susceptibility to CRCI. There was a weak correlation between some aspects of the subjective tests and the objective test scores. Advanced age and disease diagnosis longer than 10 months are associated with a heightened risk of objective cognitive impairment. Furthermore, residing in rural areas, female, married, alcohol history, SAS and SDS increases the likelihood of subjective cognitive impairment. These findings highlight the need to select appropriate assessment scales for different needs and take targeted interventions to address CRCI in patients with NPC.

Dose-response relationship of high-intensity training on global cognition in older adults with mild cognitive impairment or dementia: a systematic review with meta-analysis - the ACHIEVE-Study.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) and its subsequent progression to dementia has increased progression to dementia has increased worldwide, making it a topic of interest. of interest, and it has been observed that approximately 23% of cases are avoidable through preventable through vigorous exercise. METHODS: A systematic review with meta-analysis was conducted by searching in the PubMed, Scopus, CINAHL, and Web of Science databases. For inclusion, studies had to incorporate High Intensity Training (HIT) as a primary or significant component of the overall intervention for older adults with MCI. Out of the 611 articles identified, 14 randomized clinical trials met the criteria for inclusion in the review. RESULTS: Fourteen trials were included in the systematic review, and seven were included in the meta-analysis. A total of 1839 participants were included in the studies, with 1014 receiving a high-intensity training-based intervention, and 998 were considered in the meta-analysis. Compared to usual care or sedentary activities, the high-intensity training interventions had a positive effect on cognition, either improving it or delaying the decline (g = 0.710 (95% CI: 0.191 - 1.229; p = 0.007). Additionally, the meta-analysis determined that a frequency of 3 sessions per week (g = 0.964, CI = 0.091 - 1.837, p = 0.030) of approximately 60 minutes (g = 0.756, CI = 0.052 - 1.460, p = 0.035) each was the best dose to obtain better effects on global cognition. CONCLUSION: Low-frequency and short-duration high-intensity training interventions are sufficient to improve or at least delay the decline in global cognition.

Associations between Cognitive Impairment, Weight Status and Comorbid Conditions in Hospitalized Adults of 55 Years and Older in Guadeloupe.

Cognitive decline and comorbid conditions commonly co-occur, and these conditions can affect cognitive health. We aimed to estimate the prevalence of cognitive impairment (CI) according to weight status and to evaluate the associations between CI, weight status and comorbid conditions in adults of 55 years and older. The Abbreviated Mental Test Score (AMTS) was used. Logistic regressions were performed. Overall, 415 individuals were included. The mean age was 75.7 ± 10.1 years, and the mean BMI was 26.2 ± 6.9 kg/m2. The prevalence of CI was 20.7% in the whole study group and 31%, 24.8%, 17.7% and 10.2% in underweight, normal weight, overweight and obese individuals, respectively; p < 0.004. The low folate, vitamin D and prealbumin levels were more frequently found in individuals with CI compared with those without CI. Compared with the obese individuals, a higher odds ratio of prevalent CI was noted for underweight individuals OR 3.89 (95% CI 1.54-9.80); p = 0.004. Additionally, male gender, older age, stroke, having three or more comorbid conditions and findings of undernutrition were significantly associated with CI. Being underweight was associated with an increased risk of CI. Prevention strategies including the monitoring of nutritional status may help to prevent cognitive decline and promote healthy aging.

Association between type of menopause and mild cognitive impairment: The REDLINC XII study.

OBJECTIVE: To evaluate the association between type of menopause (spontaneous or surgical) and mild cognitive impairment (MCI). STUDY DESIGN: This study was a cross-sectional, observational, and sub-analytical investigation conducted within gynecological consultations across nine Latin American countries. METHOD: We assessed sociodemographic, clinical, and anthropometric data, family history of dementia, and the presence of MCI using the Montreal Cognitive Assessment (MoCA) tool. RESULTS: The study involved 1185 postmenopausal women with a mean age of 55.3 years and a body mass index of 26.4 kg/m2. They had an average of 13.3 years of education, and 37 % were homemakers. Three hundred ninety-nine experienced menopause before 40, including 136 with surgical menopause (bilateral oophorectomy). Out of the 786 women who experienced menopause at 40 or more years, 110 did so due to bilateral oophorectomy. There were no differences in MoCA scores among women who experienced menopause before or after the age of 40. However, lower MoCA scores were observed in women with surgical menopause than in those with spontaneous menopause (23.8 ± 4.9 vs. 25.0 ± 4.3 points, respectively, p < 0.001). Our logistic regression model with clustering of patients within countries found a significant association between MCI and surgical menopause (OR 1.47, 95 % CI: 1.01-2.16), use (ever) of menopausal hormone therapy (OR 0.33, 95 % CI: 0.21-0.50), and having >12 years of education (OR 0.21, 95 % CI: 0.14-0.30). CONCLUSION: When comparing women who experience spontaneous menopause over the age of 40 with those who undergo it before this age, there was no observed increased risk of developing MCI, while those with surgical menopause, independent of age, are more prone to cognitive decline. Women who have ever used menopausal hormone therapy have a lower MCI risk. Further research is warranted to delve deeper into this topic.

Association between cognitive impairment and socioeconomic and sociodemographic factors in Colombian older adults.

INTRODUCTION: Worldwide, because of the demographic transition, the proportion of older adults has increased, which has been reflected in an increase in the prevalence of major neurocognitive disorder (MND). This phenomenon is especially important in low- and middle-income countries such as Colombia, given the high economic and social costs it entails. The objective was to analyse the association between socioeconomic variables with the presence of cognitive impairment in Colombian older adults. METHODS: The records of 23,694 adults over 60 years-of-age surveyed for SABE Colombia 2015, that took a stratified sample by conglomerates and were representative of the adult population over 60 years-of-age. This instrument assessed cognitive impairment using the abbreviated version of the Minimental (AMMSE) and collected information on multiple socioeconomic variables. RESULTS: 19.7% of the older adults included in the survey were reviewed with cognitive impairment by presenting a score <13 in the AMMSE. There was a higher prevalence of cognitive impairment in women (21.5%) than in men (17.5%). The socioeconomic variables were shown to impact the prevalence of deterioration, especially being currently working (OR = 2.74; 95%CI, 2.43-3.09) as a risk factor and having attended primary school as a protective factor (OR = 0.30; 95%CI, 0.28-0.32), differentially according to gender. CONCLUSIONS: An association between socioeconomic and sociodemographic factors with cognitive impairment in Colombian older adults was evidenced. Despite the above, a differential impact dependent on sex is suggested.

Mapping brain morphology to cognitive deficits: a study on PD-CRS scores in Parkinson's disease with mild cognitive impairment.

Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort. Materials and methods: This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (n = 36) and PD-MCI (n = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer. Results: Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm2 cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions. Conclusion: PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.

Gut Microbiome Is Related to Cognitive Impairment in Peritoneal Dialysis Patients.

Gut microbiota disturbances may influence cognitive function, increasing uremic toxins and inflammation in dialysis patients; therefore, we aimed to evaluate the association of the gut microbiota profile with cognitive impairment (CI) in patients on automated peritoneal dialysis (APD). In a cross-sectional study, cognitive function was evaluated using the Montreal Cognitive Assessment in 39 APD patients and classified as normal cognitive function and CI. The gut microbiota was analyzed using the 16S rRNA gene sequencing approach. All patients had clinical, biochemical and urea clearance evaluations. Eighty-two percent of patients were men, with a mean age of 47 ± 24 years and 11 (7-48) months on PD therapy; 64% had mild CI. Patients with CI were older (53 ± 16 vs. 38 ± 14, p = 0.006) and had a higher frequency of diabetes mellitus (56% vs. 21%, p = 0.04) and constipation (7% vs. 48%, p = 0.04) and lower creatinine concentrations (11.3 ± 3.7 vs. 14.9 ± 5.4, p = 0.02) compared to normal cognitive function patients. Patients with CI showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter and Anaerotruncus, while patients without CI had a greater abundance of Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) > 2.5; p < 0.05). After glucose and age adjustment, Odoribacter was still associated with CI. In conclusion, patients with CI had a different gut microbiota characterized by the higher abundance of indole-producing and mucin-fermenting bacteria compared to normal cognitive function patients.

Dietary patterns in mild cognitive impairment and dementia in older adults from Yucatan, Mexico.

Background: Some dietary patterns and dietary components have an important role in preventing and helping to improve patients' quality of life of individuals with Mild Cognitive Impairment (MCI) and dementia. In Mexico, it is unknown what the dietary patterns are among older adults with MCI and dementia. We aimed to identify the dietary patterns of older adults with MCI and dementia living in Yucatan, Mexico. Methods: A cross-sectional study was carried out among 39 patients as controls and 34 individuals as cases (MCI and dementia). A food frequency questionnaire collected diet information, anthropometric and clinical parameters, and lifestyle characteristics. The dietary patterns were evaluated through Partial Least-Squares Discriminant Analysis (PLS-DA). Results: The food groups that showed discrimination between groups and were classified into the dietary patterns of MCI and dementia individuals were "pastries and cookies," "soups," and "legumes." The dietary pattern of older adults without cognitive impairment was characterized by "nuts and seeds," "candies," "vegetables," "coffee and tea," and "water." The consumption of "pastries and cookies" showed an increasing correlation with serum insulin levels (r = 0.36, p = 0.01), and "soups" showed an inverse correlation with total cholesterol levels (r = -0.36, p = 0.02) in patients with MCI and dementia. In controls, there is a positive correlation between the consumption of "nuts and seeds" (r = 0.333, p = 0.01) and "vegetables" (r = 0.32, p = 0.02) with levels of urea; "coffee and tea" showed a positive association with levels of insulin (r = 0.378, p = 0.05). Conclusion: The dietary pattern of individuals with MCI and dementia has some nutritional deficiencies. Including an adequate intake of vegetables, fruits, and protein could improve the quality of life of subjects living with these conditions in Yucatan, Mexico.

Hypertension Prevalence, Treatment, and Control 90 Days After Acute Stroke Among Mexican American and Non-Hispanic White Adults.

BACKGROUND: High blood pressure (BP) increases recurrent stroke risk. METHODS AND RESULTS: We assessed hypertension prevalence, treatment, control, medication adherence, and predictors of uncontrolled BP 90 days after ischemic or hemorrhagic stroke among 561 Mexican American and non-Hispanic White (NHW) survivors of stroke from the BASIC (Brain Attack Surveillance in Corpus Christi) cohort from 2011 to 2014. Uncontrolled BP was defined as average BP ≥140/90 mm Hg at 90 days poststroke. Hypertension was uncontrolled BP or antihypertensive medication prescribed or hypertension history. Treatment was antihypertensive use. Adherence was missing zero antihypertensive doses per week. We investigated predictors of uncontrolled BP using logistic regression adjusting for patient factors. Median (interquartile range) age was 68 (59-78) years, 64% were Mexican American, and 90% of strokes were ischemic. Overall, 94.3% of survivors of stroke had hypertension (95.6% Mexican American versus 92.0% non-Hispanic White; P=0.09). Of these, 87.9% were treated (87.3% Mexican American versus 89.1% non-Hispanic White; P=0.54). Among the total population, 38.3% (95% CI, 34.4%-42.4%) had uncontrolled BP. Among those with uncontrolled BP prescribed an antihypertensive, 84.5% reported treatment adherence (95% CI, 78.8%-89.3%). Uncontrolled BP 90 days poststroke was less likely in patients with stroke who had a primary care physician (adjusted odds ratio [aOR], 0.45 [95% CI, 0.24-0.83]; P=0.01), greater stroke severity (aOR per-1-point-higher National Institutes of Health Stroke Scale score, 0.96 [95% CI, 0.93-0.99]; P=0.02), or more depressive symptoms (aOR per-1-point-higher Personal Health Questionnaire Depression Scale-8 score, 0.95 [95% CI, 0.92-0.99] among those with a history of hypertension at baseline; P=0.009). CONCLUSIONS: Greater than one third of survivors of stroke have uncontrolled BP at 90 days poststroke in this population-based study. Interventions are needed to improve BP control after stroke.

Population-level trends in self-reported healthcare utilization among older adults in Mexico with and without cognitive impairment.

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico. METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and being screened for cholesterol, diabetes, and hypertension in the past two years. Cognitive impairment was defined using a modified version of the Cross Cultural Cognitive Examination that assessed verbal memory, visuospatial and visual scanning. Total sample included 5,673 participants with cognitive impairment and 34,497 without cognitive impairment interviewed between 2001 and 2018. Generalized Estimating Equation models that adjusted for time-varying demographic and health characteristics and included an interaction term between time and cognitive status were used. RESULTS: For all participants, the risk for one or more overnight hospital stays, doctor visits, and dental visits in the past year, and being screened for diabetes, hypertension, and high cholesterol increased from 2001 to 2012 and leveled off or decreased in 2015 and 2018. Conversely, seeing a homeopathic doctor decreased. Cognitive impairment was associated with higher risk of hospitalization (RR = 1.13, 1.03-1.23) but lower risk of outpatient services (RR = 0.95, 0.93-0.97), cholesterol screening (RR = 0.93, 0.91-0.96), and diabetes screening (RR = 0.95, 0.92-0.97). No significant difference was observed in the use of pharmacists, homeopathic doctors, or folk healers based on cognitive status. Interaction effects indicated participants with cognitive impairment had lower risk for dental visits and hypertension screening but that these trajectories differed over time compared to participants without cognitive impairment. CONCLUSIONS: We identified distinct population-level trends in self-reported healthcare utilization and differences according to cognitive status, particularly for elective and screening services. These findings highlight the necessity for policy interventions to ensure older adults with cognitive impairment have their healthcare needs met.

Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial.

BACKGROUND: The increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant. OBJECTIVE: To assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI. METHODS: Thirty-four older adults (men, women) with MCI were randomized to the experimental group (n = 17; 75.41 ± 5.76) or control (n = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions). RESULTS: Between groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups (p < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p = 0.28; experimental, p = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level. CONCLUSIONS: The application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

Two-Year Longitudinal Outcomes of Subjective Cognitive Decline in Hispanics Compared to Non-hispanic Whites.

BACKGROUND: Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW). METHODS: Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance. RESULTS: Hispanics were at increased risk of progression to MCI (OR: 6.10, 95% CI 1.09-34.20, P = .040). Hispanic participants endorsed more depressive symptoms at baseline (P = .048) that worsened more longitudinally (OR: 3.16, 95% CI 1.18-8.51, P = .023). Hispanic participants had increased SCD complaints on the Brief Cognitive Rating Scale (BCRS) (ß = .40 SE: .17, P = .023), and in specific BCRS domains: concentration (ß = .13, SE: .07, P = .047), past memory (ß = .13, SE: .06, P = .039) and functional abilities (ß = .10, SE: .05, P = .037). In objective cognitive performance, Hispanic ethnicity associated with decline in MMSE (ß = -.27, SE: .13, P = .039), MoCA (ß = -.80 SE: .34, P = .032), Trails A (ß = 2.75, SE: .89, P = .002), Trails B (ß = 9.18, SE: 2.71, P = .001) and Guild Paragraph Recall Delayed (ß = -.80 SE: .28, P = .005). Conclusions: Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group.

The impact of education level and socioeconomic status on the association between depressive symptoms and memory in an older population in Latin America: An exploratory analysis from the Brazilian Longitudinal Study of Aging (ELSI-BRAZIL).

Purpose: The globally increasing older population raises concerns about age-related conditions, including cognitive impairment and depressive symptoms. In Latin America, nearly one-third of the population is affected by either of these conditions. However, data investigating the association between cognitive impairment and depressive symptoms, particularly in Brazil, are limited to small-scale studies that have not carefully examined the critical effects of variables such as education level and socioeconomic status on this relationship. We aimed at exploring this association in a representative population-based cohort. Methods: We used the Brazilian Longitudinal Study of Aging (ELSI-BRAZIL) database to examine the relationship between depressive symptoms and cognitive impairment in Brazilian older adults, adjusted for potential confounders. Direct acyclic graphs and multivariable linear regression were used to build our model. Depressive symptoms were measured using a short version of the Center for Epidemiologic Studies Scale (CES D-8), and combined memory recall test as a surrogate of cognitive impairment. Results: The study included 8280 participants. Only education level was identified as a confounder for the relationship between memory loss and depressive symptoms. After adjusting for age, sex, and education level, there was strong evidence for a negative association between depressive symptoms and memory performance. For every 5-unit increase in the CES D-8 score, there was a reduction in memory capacity, translating to a loss of approximately one word in the combined words recall test (mean - 0.18, 95% CI -0.22; -0.15, P < 0.001). In addition, we found strong evidence for an interaction between socioeconomic status and depressive symptoms. Subjects belonging to medium socioeconomic status (SES) showed more pronounced memory decline, when compared to those with lower SES (mean - 0.28, 95% CI -0.42 to -0.14, P < 0.001). Conclusions: In adults aged over 50, after adjusting for sex, age, and educational level, a 5-unit increase in CES D-8 score is associated with loss of one point in the combined memory recall test. This association seems to be confounded by educational level and significantly modified by socioeconomic status.

Socioeconomic determinants of cognition among older adults in the Brazilian longitudinal study of aging (ELSI-Brazil): a life-course approach.

BACKGROUND: The prevalence of cognitive impairment no dementia (CIND) and dementia appears to be higher in low- and middle-income countries (LMICs) compared to high-income economies. Yet few nationally representative studies from Latin American LMICs have investigated life-course socioeconomic factors associated with the susceptibility to these two cognitive conditions. Hence, the present study aimed to examine the associations of early- (education and food insecurity), mid- (employment stability), and late-life (personal income and household per capita income) socioeconomic determinants of CIND and dementia among older adults from Brazil, while simultaneously exploring whether sex plays an effect-modifier role on these associations. METHODS: This population-based study comprised a nationally representative sample of older adults (N = 5,249) aged 60 years and over from the Brazilian Longitudinal Study of Aging (ELSI-Brazil). We fitted multinomial regressions and estimated odds ratios with the respective 95% confidence intervals (CIs). RESULTS: In multivariate analyses, participants with more years of early-life education (0.89, 95% CI [0.81, 0.97]) and mid-life employment stability (0.97, 95% CI [0.96, 0.99]) and higher late-life household per capita income (0.70, 95% CI [0.51, 0.95) were less likely to have dementia. Regarding CIND, more years of mid-life employment stability (0.97, 95% CI [0.96, 0.98]) was the only determinant to confer protection. Notably, secondary sex-based analyses showed the higher the early-life educational attainment, the lower the odds of dementia in women (0.81, 95% CI [0.75, 0.87]) but not in men (1.00, 95% CI [0.86, 1.16]). CONCLUSIONS: These findings may have implications for population health and health policy by advancing our understanding of socioeconomic determinants of CIND and dementia, especially in Latin America.

Amyloid profile is associated with sleep quality in preclinical but not in prodromal Alzheimer's disease older adults.

BACKGROUND: Few studies have assessed whether neuropathological markers of AD in the preclinical and prodromal stages are associated with polysomnographic changes and obstructive sleep apnea (OSA). METHODS: This was a cross-sectional, case-control study of older adults (≥60 years) without relevant clinical and psychiatric comorbidities selected randomly from a cohort of individuals without dementia in a tertiary university hospital in São Paulo, Brazil. They underwent neuropsychological evaluation for clinical diagnosis and were allocated into two samples: cognitively unimpaired (CU) and mild cognitive impairment (MCI). Also, they underwent PET-PiB to determine the amyloid profile and all-night in-lab polysomnography. For each sample, we compared polysomnographic parameters according to the amyloid profile (A+ vs A-). RESULTS: We allocated 67 participants (mean age 73 years, SD 10,1), 70 % females, 14 ± 5 years of education, into two samples: CU (n = 28, 42.4 %) and MCI (n = 39, 57.6 %). In the CU sample, the group A+ (n = 9) showed worse sleep parameters than A- (n = 19) (lower total sleep time (p = 0.007), and sleep efficiency (p = 0.005); higher sleep onset latency (p = 0.025), wake time after sleep onset (p = 0.011), and arousal index (AI) (p = 0.007)), and changes in sleep structure: higher %N1 (p = 0.005), and lower %REM (p = 0.006). In the MCI sample, MCI A-had higher AI (p = 0.013), respiratory disturbance index (p = 0.025, controlled for age), and higher rates of severe OSA than A+. DISCUSSION: The amyloid profile was associated with polysomnographic markers of worse sleep quality in individuals with preclinical AD but not with prodromal AD, probably due to the higher frequencies of severe OSA.

[Association between previous appendectomy and cognitive impairment in adults: a case-control study]. / Vliyanie predshestvuyushchei appendektomii na kognitivnye narusheniya u vzroslykh: issledovanie «sluchai-kontrol'¼.

OBJECTIVE: To determine the relationship between appendectomy and cognitive impairment in adults aged 50-70 years. MATERIAL AND METHODS: A case-control study was carried out with 270 patients between May and July 2023. Ninety cases (with cognitive impairment) and 180 controls (without impairment), diagnosed by the Montreal Cognitive Assessment (MoCA), were assessed. RESULTS: 31.11% of the total cases with cognitive impairment were submitted to an appendectomy, with an average of 25 years since surgery. Regarding other surgeries: 40% with impairment underwent cholecystectomy and 23.33% reported other operations. The analysis revealed significant differences in age, body mass index, hypertension, diabetes and smoking between the groups. However, there was no significant difference by gender. Logistic regression analysis highlighted that age and past appendectomy were strongly associated with cognitive impairment, with an Odds Ratio (OR) of 1.20 and 12.91, respectively. Associations were also found with cholecystectomy (OR 7.33), other surgeries (OR 13.39) and smoking (OR 6.91). CONCLUSION: Appendectomy might be a significant risk factor for cognitive impairment in adults aged 50-70 years.

Monoclonal antibodies and aptamers: The future therapeutics for Alzheimer's disease.

Alzheimer's disease (AD) is considered the most common and prevalent form of dementia of adult-onset with characteristic progressive impairment in cognition and memory. The cure for AD has not been found yet and the treatments available until recently were only symptomatic. Regardless of multidisciplinary approaches and efforts made by pharmaceutical companies, it was only in the past two years that new drugs were approved for the treatment of the disease. Amyloid beta (Aß) immunotherapy is at the core of this therapy, which is one of the most innovative approaches looking to change the course of AD. This technology is based on synthetic peptides or monoclonal antibodies (mAb) to reduce Aß levels in the brain and slow down the advance of neurodegeneration. Hence, this article reviews the state of the art about AD neuropathogenesis, the traditional pharmacologic treatment, as well as the modern active and passive immunization describing approved drugs, and drug prototypes currently under investigation in different clinical trials. In addition, future perspectives on immunotherapeutic strategies for AD and the rise of the aptamer technology as a non-immunogenic alternative to curb the disease progression are discussed.