Risk Factor For Cognitive Decline Research Articles

Executive functions in mid-life adults with mild sensorineural hearing loss compared with age-matched controls with normal hearing

PurposeThis study explores the relationship between sensorineural hearing loss (SNHL) in mid-life adults and cognitive function, focusing on executive functions. Given the projected rise in dementia cases, identifying modifiable risk factors for cognitive decline is imperative. SNHL has emerged as a potential risk factor, with hearing loss accounting for a substantial portion of dementia cases. However, the cognitive implications of SNHL in mid-life adults are not well understood.MethodThe study examined 50 participants, 25 with bilateral unaided mild SNHL (AHL) and 25 with normal hearing (ANH). A battery of audiological assessments and cognitive tests, including the Trail Making Test (TMT), was administered. TMT measures included direct scores (completion time and errors) and derived scores (difference, ratio, proportion, sum, and multiplication scores).ResultsThe AHL group displayed significantly poorer peripheral hearing compared to the ANH group, as reflected in pure-tone audiometry, speech reception thresholds, and speech identification scores. Significant differences were observed in all direct and derived TMT measures except for the ratio and proportion scores. This suggests that while overall cognitive disturbances were evident in the AHL group, they were not exclusive to executive function deficits. Notably, we did not identify any statistically significant effects of hypertension, diabetes, smoking, alcohol consumption, or physical activity on TMT scores.ConclusionThis study highlights the potential impact of SNHL on cognitive function in mid-life adults. Mid-life SNHL is associated with cognitive differences, emphasizing its role as a modifiable risk factor for future cognitive decline. This research underlines the need for further investigation into the cognitive effects of aided hearing and a multidisciplinary approach to understanding these alterations in cognitive function.

Establishment and evaluation of a clinical prediction model for cognitive impairment in patients with cerebral small vessel disease

BackgroundThere are currently no effective prediction methods for evaluating the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD).AimsTo investigate the risk factors for cognitive dysfunction in patients with CSVD and to construct a risk prediction model.MethodsA retrospective study was conducted on 227 patients with CSVD. All patients were assessed by brain magnetic resonance imaging (MRI), and the Montreal Cognitive Assessment (MoCA) was used to assess cognitive status. In addition, the patient’s medical records were also recorded. The clinical data were divided into a normal cognitive function group and a cognitive impairment group. A MoCA score < 26 (an additional 1 point for education < 12 years) is defined as cognitive dysfunction.ResultsA total of 227 patients (mean age 66.7 ± 6.99 years) with CSVD were included in this study, of whom 68.7% were male and 100 patients (44.1%) developed cognitive impairment. Age (OR = 1.070; 95% CI = 1.015 ~ 1.128, p < 0.05), hypertension (OR = 2.863; 95% CI = 1.438 ~ 5.699, p < 0.05), homocysteine(HCY) (OR = 1.065; 95% CI = 1.005 ~ 1.127, p < 0.05), lacunar infarct score(Lac_score) (OR = 2.732; 95% CI = 1.094 ~ 6.825, P < 0.05), and CSVD total burden (CSVD_score) (OR = 3.823; 95% CI = 1.496 ~ 9.768, P < 0.05) were found to be independent risk factors for cognitive decline in the present study. The above 5 variables were used to construct a nomogram, and the model was internally validated by using bootstrapping with a C-index of 0.839. The external model validation C-index was 0.867.ConclusionsThe nomogram model based on brain MR images and clinical data helps in individualizing the probability of cognitive impairment progression in patients with CSVD.

Impact of cumulative exposure to anticholinergic and sedative drugs on cognition in older adults: a memory clinic cohort study

BackgroundLong-term exposure to anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline.MethodsA cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970). Drug Burden Index was linearly cumulated until each MMSE measurement and was used to categorise patients according to their level of exposure (no exposure, moderate, or high). The longitudinal association between Drug Burden Index and MMSE was assessed using a multivariate linear mixed model, adjusted for age, education level, anxiety disorders, depressive disorders, functional autonomy, and behavioural disorders.ResultsOverall, 1,970 patients were included with a mean follow-up duration of 2.78 years (± 1.54) and 2.99 visits per patients (5,900 MMSE + Drug Burden Index measurements collected). At baseline, 68.0% of patients had moderate cumulative anticholinergic and sedative drug exposure and a mean MMSE of 21.1. MMSE decrease was steeper in patients with moderate and high Drug Burden Index ( -1.74 and -1.70/year, respectively) than in patients with no exposure (-1.26/year) after adjusting for age, education, anxiety and depressive disorders, functional autonomy, and behavioural disorders (p < 0.01).ConclusionsLong-term exposure to anticholinergic and sedative drugs is associated with steeper cognitive decline. Medication review focusing on de-prescribing these drugs could be implemented early to reduce cognitive impairment.

Analysis of changes in social isolation, loneliness, or both, and subsequent cognitive function among older adults: Findings from a nationwide cohort study

AbstractINTRODUCTIONThe study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function.METHODSData were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine‐category variable to represent the joint changes. Tobit regression models and Cox models were performed.RESULTSIncident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p &lt; 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p &lt; 0.001). Notably, short‐term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p &lt; 0.05).DISCUSSIONShort‐term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment.Highlights Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short‐term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

Depression, loneliness, and lower social activity as partial mediators of the association between visual impairment and cognitive decline.

Sensory impairment is a hypothesized risk factor for cognitive decline; however, the psychosocial pathways are not well understood. We evaluated whether the association between visual impairment (VI) and cognitive decline was partially mediated via depressive symptoms, loneliness, or social activity. We used data from 2601 older adults enrolled in the Memory and Aging Project in 1997 and the Minority Aging Research Study in 2004 with neuropsychological tests across five domains measured annually for up to 16years. VI was assessed with the Rosenbaum Pocket Vision Screener. Depressive symptoms, loneliness, and social activity were self-reported using validated scales. We used structural equation models to estimate the associations of VI with baseline and change in cognitive function, directly and indirectly through each mediator (depressive symptoms, loneliness, and social activity). We evaluated mediation via "psychological distress" using a latent variable combining depressive symptoms and loneliness. The association between VI and global cognitive decline was mediated via lower social activity (indirect effect) [95% confidence interval (CI)] of linear slope: -0.025 (-0.048, -0.011), via loneliness (-0.011 [95% CI: -0.028, -0.002]), and via psychological distress (-0.017 [95% CI: -0.042, -0.003]). We did not find sufficient evidence for mediation via depressive symptoms alone. The harmful effect of VI on cognitive decline may be partially mediated through loneliness and lower social activity.

A multidomain lifestyle intervention to maintain optimal cognitive functioning in Dutch older adults—study design and baseline characteristics of the FINGER-NL randomized controlled trial

BackgroundEvidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in older people without dementia is mixed. Embedded in the World-Wide FINGERS initiative, FINGER-NL aims to investigate the effectiveness of a 2-year multidomain lifestyle intervention on cognitive functioning in older Dutch at risk individuals.MethodsMulti-center, randomized, controlled, multidomain lifestyle intervention trial with a duration of 24 months. 1210 adults between 60–79 years old with presence of ≥ 2 modifiable risk factors and ≥ 1 non-modifiable risk factor for cognitive decline were recruited between January 2022 and May 2023 via the Dutch Brain Research Registry and across five study sites in the Netherlands. Participants were randomized to either a high-intensity or a low-intensity intervention group. The multidomain intervention comprises a combination of 7 lifestyle components (physical activity, cognitive training, cardiovascular risk factor management, nutritional counseling, sleep counseling, stress management, and social activities) and 1 nutritional product (Souvenaid®) that could help maintain cognitive functioning. The high-intensity intervention group receives a personalized, supervised and hybrid intervention consisting of group meetings (on-site and online) and individual sessions guided by a trained lifestyle coach, and access to a digital intervention platform that provides custom-made training materials and selected lifestyle apps. The low-intensity intervention group receives bi-monthly online lifestyle-related health advice via the digital intervention platform. Primary outcome is 2-year change on a cognitive composite score covering processing speed, executive function, and memory.ResultsWithin 17 months, participant recruitment has been successfully completed (N = 1210; mean age: 67.7 years (SD: 4.6); 64% female). Modifiable risk factors commonly present at baseline were physical inactivity (89%), low mental/cognitive activity (50%), low social engagement (39%), hypertension (39%) and high alcohol consumption (39%). The mean body mass index of participants was 28.3 (SD: 4.2) and the total serum cholesterol was 5.4 mmol/L (SD: 1.2).ConclusionsBaseline lifestyle and clinical measurements showed successful recruitment of participants with sufficient potential for prevention. Results of FINGER-NL will provide further insight into the efficacy of a multidomain lifestyle intervention to prevent cognitive decline in older adults.Trial registrationClinicalTrials.gov (ID: NCT05256199)/2022–01-11.

Correlation between hearing loss and mild cognitive impairment in the elderly population: Mendelian randomization and cross-sectional study.

Hearing loss and tinnitus have been linked to mild cognitive impairment (MCI); however, the evidence is constrained by ethical and temporal constraints, and few prospective studies have definitively established causation. This study aims to utilize Mendelian randomization (MR) and cross-sectional studies to validate and analyze this association. This study employs a two-step approach. Initially, the genetic data of the European population from the Genome-wide association studies (GWAS) database is utilized to establish the causal relationship between hearing loss and cognitive impairment through Mendelian randomization using the inverse variance weighted (IVW) method. This is achieved by identifying strongly correlated single nucleotide polymorphisms (SNPs), eliminating linkage disequilibrium, and excluding weak instrumental variables. In the second step, 363 elderly individuals from 10 communities in Qingdao, China are assessed and examined using methods questionnaire survey and pure tone audiology (PTA). Logistic regression and multiple linear regression were used to analyze the risk factors of MCI in the elderly and to calculate the cutoff values. Mendelian randomization studies have shown that hearing loss is a risk factor for MCI in European populations, with a risk ratio of hearing loss to MCI loss of 1. 23. The findings of this cross-sectional study indicate that age, tinnitus, and hearing loss emerged as significant risk factors for MCI in univariate logistic regression analysis. Furthermore, multivariate logistic regression analysis identified hearing loss and tinnitus as potential risk factors for MCI. Consistent results were observed in multiple linear regression analysis, revealing that hearing loss and age significantly influenced the development of MCI. Additionally, a notable finding was that the likelihood of MCI occurrence increased by 9% when the hearing threshold exceeded 20 decibels. This study provides evidence from genomic and epidemiological investigations indicating that hearing loss may serve as a risk factor for cognitive impairment. While our epidemiological study has found both hearing loss and tinnitus as potential risk factors for cognitive decline, additional research is required to establish a causal relationship, particularly given that tinnitus can manifest as a symptom of various underlying medical conditions.

The Taxonomy of Subjective Cognitive Decline: Proposal and First Clinical Evidence from the Geneva Memory Clinic Cohort

Introduction: Subjective cognitive decline (SCD) is characterized by subjective cognitive concerns without objective cognitive impairment and is considered a risk factor for cognitive decline and dementia. However, most SCD patients will not develop neurodegenerative disorders, yet they may suffer from minor psychiatric, neurological, or somatic comorbidities. The aim of the present study was to provide a taxonomy of the heterogeneous SCD entity and to conduct a preliminary validation using data from a memory clinic sample. Methods: Participants were fifty-five SCD individuals consecutively recruited at the Geneva Memory Center. Based on clinical reports, they were classified into three clinically pre-defined subgroups: (i) those with psychological or psychiatric comorbidities (Psy), (ii) those with somatic comorbidities (SomCom), (iii) and those with no apparent cause (NAC). Baseline demographics, clinical, cognitive, and biomarker differences among the SCD subgroups were assessed. Longitudinal cognitive changes (average 3 years follow-up) were modeled using a linear mixed model. Results: Out of the 55 SCD cases, 16 were SomCom, 18 Psy, and 21 NAC. 47% were female, mean age was 71 years. We observed higher frequency of APOE ε4 carriers in NAC (53%) compared to SomCom (14%) and Psy (0%, p = 0.023) and lower level of plasma Aβ42 in NAC (6.8 ± 1.0) compared to SomCom (8.4 ± 1.1; p = 0.031). SomCom subjects were older (74 years) than Psy (67 years, p = 0.011), and had greater medial temporal lobe atrophy (1.0 ± 1.0) than Psy (0.2 ± 0.6) and NAC (0.4 ± 0.5, p = 0.005). SomCom has worse episodic memory performances (14.5 ± 3.5) than Psy (15.8 ± 0.4) and NAC (15.8 ± 0.7, p = 0.032). We observed a slightly steeper, yet not statistically significant, cognitive decline in NAC (β = −0.48) compared to Psy (β = −0.28) and SomCom (β = −0.24). Conclusions: NAC features a higher proportion of APOE ε4 carriers, lower plasma Aβ42 and a trend towards steeper cognitive decline than SomCom and Psy. Taken together, these findings suggest that NACs are at higher risk of cognitive decline due to AD. The proposed clinical taxonomy might be implemented in clinical practice to identify SCD at higher risk. However, such taxonomy should be tested on an independent cohort with a larger sample size.

Relationship between Social Participation and Cognitive Impairment in Low-Educated Older Adults Based on Indonesian Family Life Survey-5.

The increasing older adult population requires attention in terms of education and health, as higher education levels contribute to cognitive reserve and may protect against age-related cognitive impairment. Cognitive reserve is an individual's cognitive flexibility in using cognitive functions affected by brain aging, neurological diseases, and injury. Indonesia has a high prevalence of low-educated older adults, which strongly correlates with progressive cognitive impairment. Identifying risk factors for cognitive decline in this population is crucial. This study determines the factors affecting cognitive impairment in low-educated older adults using cross-sectional data from the Indonesian Family Life Survey-5. This descriptive study analyzed 2,313 low-educated older adults ≥60 years old. Univariate and bivariate analyses were used to describe the sample and identify the relationships between categorical variables. Logistic regression identified the most significant factor affecting cognitive impairment. The prevalence of cognitive impairment in low-educated older adults is 22.6%. The chi-square test revealed significant relationships between those who are aged 75 years, a status other than married, female, living in rural areas, and not participating in social activities. Age is the most prominent factor affecting cognitive impairment in such adults (P<0.001; adjusted odds ratio, 3.232; 95% confidence interval, 2.500-4.180). Cognitive impairment in the aforementioned adults is associated with being ≥75 years old, being a status other than married, being female, living in rural areas, and not participating in social activities. After controlling other variables, low-educated older adults who participated in at least ≥1 social activity in the last 12 months experienced cognitive impairment 0.64 times compared to those who did not participate in social activities.

Modifiable Risk Factors Associated With Cognitive Decline in Late Life Depression: Findings From the Canadian Longitudinal Study on Aging: Facteurs de risque modifiables associés au déclin cognitif dans la dépression en fin de vie : constatations de l'Étude longitudinale canadienne sur le vieillissement.

Depression in later life is associated with a two-fold increased risk of dementia. It is not clear to what extent potentially modifiable risk factors account for this association. Older adults (age 50 + ) with objective health measures (n = 14,014) from the Canadian Longitudinal Study on Aging were followed for a mean duration of 35 months. Linear regression analyses were used to determine if clinically significant depression (Centre for Epidemiologic Studies Depression scale score (CESD) ≥ 10) was associated with global cognitive decline, assessed with a neuropsychological battery during follow-up, and if modifiable risk factors mediated this association. Depression was associated with an excess of risk factors for cognitive decline including: vascular disease, hypertension, diabetes, apnoea during sleep, higher body mass index, smoking, physical inactivity and lack of social participation. In regression analyses depression remained independently associated with cognitive decline over time (beta -0.060, P = 0.038) as did cerebrovascular disease (beta -0.197, P < 0.001), HbA1C (beta -0.059, P < 0.001), visual impairment (beta -0.070, P = 0.007), hearing impairment (beta -0.098, P < 0.001) and physical inactivity (beta -0.075, P = 0.014). In mediation analyses, we found that cerebrovascular disease (z = -3.525, P < 0.001), HbA1C (z = -4.976, P < 0.001) and physical inactivity (z = -3.998, P < 0.001) partially mediated the association between depression and cognitive decline. In this large sample of Canadian older adults incorporating several objective health measures, older adults with depression were at increased risk of cognitive decline and had an excess of potentially modifiable risk factors. Clinicians should pay particular attention to control of diabetes, physical inactivity and risk factors for cerebrovascular disease in older adults presenting with depression as they can contribute to accelerated cognitive decline and may be addressed during routine clinical care.

Multi-night acoustic stimulation is associated with better sleep, amyloid dynamics, and memory in older adults with cognitive impairment.

Sleep is a potential early, modifiable risk factor for cognitive decline and dementia. Impaired slow wave sleep (SWS) is pronounced in individuals with cognitive impairment (CI). Cognitive decline and impairments of SWS are bi-directionally linked in a vicious cycle. SWS can be enhanced non-invasively using phase-locked acoustic stimulation (PLAS), potentially breaking this vicious cycle. Eighteen healthy older adults (HC, agemean±sd, 68.3 ± 5.1) and 16 older adults (agemean±sd, 71.9 ± 3.9) with CI (Montreal Cognitive Assessment ≤ 25) underwent one baseline (sham-PLAS) night and three consecutive stimulation nights (real-PLAS). EEG responses and blood-plasma amyloid beta Aβ42/Aβ40 ratio were measured pre- and post-intervention, as was episodic memory. The latter was again evaluated 1week and 3months after the intervention. In both groups, PLAS induced a significant electrophysiological response in both voltage- and time-frequency analyses, and memory performance improved in association with the magnitude of this response. In the CI group, both electrophysiological and associated memory effects were delayed compared to the healthy group. After 3 intervention nights, electrophysiological response to PLAS was no longer different between CI and HC groups. Only in the CI sample, stronger electrophysiological responses were significantly associated with improving post-intervention Aβ42/Aβ40 ratios. PLAS seems to improve SWS electrophysiology, memory, and amyloid dynamics in older adults with CI. However, effects on memory require more time to unfold compared to healthy older adults. This indicates that PLAS may become a potential tool to ameliorate cognitive decline, but longer interventions are necessary to compensate for declining brain integrity. This study was pre-registered (clinicaltrials.gov: NCT04277104).

Ventromedial frontoinsular connectivity is associated with long-term smoking behavior change in aging

Abstract A central question in the field of cognitive aging and behavioral neuroscience is what enables some individuals to successfully change their behavior more than others? Smoking is a significant risk factor for cognitive decline, particularly in vulnerable populations, including those who are at an elevated risk for Alzheimer’s disease (AD). Developing effective smoking reduction strategies is therefore a public health priority. The goal of the current study is to better understand the brain mechanisms underlying long-term smoking behavior change in cognitively normal, but at-risk, older adults. Neuroimaging and human lesion studies have implicated the insula and its functional network in subjective interoceptive awareness of cigarette craving and smoking-cue reactivity. We sought to characterize the extent to which anterior insular resting-state functional connectivity (RSFC) MRI predicted long-term smoking reduction (mean: 2.7 years, range 8 months–4 years) using a seed-to-voxel approach. Twenty-three (18 women; 26% APOE4 carriers; 61.5 years, SD = 3.7) cognitively unimpaired older individuals who smoked cigarettes at their baseline visit and have a first-degree family history of AD (at least one parent or multiple siblings affected) were included from a prospective longitudinal cohort, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) in the current study. We found that reduced long-term smoking behavior was associated with enhanced antagonistic RSFC between bilateral anterior insula (aINS) and ventromedial prefrontal cortex (vmPFC). In a second pre-registered replication study within a larger, independent sample of 118 cognitively normal older adults who smoked cigarettes at baseline from the UK Biobank (73 women; 27.9% APOE4 carriers; 60.3 years, SD = 2.7), we found that baseline enhanced antagonistic RSFC between anterior insula and vmPFC predicted long-term smoking reduction (mean 5.2 years; ranging from 3 years to 7 years). To our knowledge, this is the largest study to examine the neural substrates of long-term smoking cessation in human aging. Our results suggest that antagonistic RSFC between aINS and vmPFC is a brain marker of future smoking reduction and disease prevention in older adults at risk for AD.

ASSOCIATION OF OFFICE AND AMBULATORY BLOOD PRESSURE MONITORING WITH COGNITIVE FUNCTION AND DEMENTIA PREVALENCE

Objective: Blood pressure (BP) is an important risk factor for cognitive decline and dementia. However, it is unclear which measures of BP obtained from office and ambulatory BP monitoring assessments are better related with cognition and dementia. Therefore, we evaluated the association of office and ambulatory BP measures with cognitive function and dementia at baseline. Design and method: We included baseline information of 1435 participants aged 50y or older from a population-based study whom underwent 24-h ambulatory BP monitoring, cognitive function, and neurological assessments. Office and ambulatory BP monitoring measures included systolic BP level and short-term variability quantified using the average real variability (ARV) index. Cognitive function examination included the minimental state examination (MMSE) and selective reminder tests ([SRL], total retrieval, long-term retrieval, and delayed recall). Dementia was a clinical dementia rating scale equal or higher than 1. We performed adjusted logistic and linear regression models to evaluate the association of office and ambulatory BP monitoring measures with cognitive function and dementia. Results: The mean age was 63.8±10.3 and 69.1% (n=963) were women. The prevalence of dementia was 3.21 (n=46). In adjusted logistic regression models, only ARV of the 24-h (odds ratios [OR] per +1-standard deviation [SD] increase in ARV, 1.42; 95% confidence interval [CI], 1.07-1.88) and nighttime (OR, 1.37; 95% CI, 1.05-1.78) systolic BP were associated with dementia at baseline. In adjusted linear regression models, only ARV was associated with lower scores in the MMSE and the SRL tests (adjusted-mean scores per +1SD increase in ARV ranged from -0.09 to -0.06 points; P values below 0.027). These associations remained after models were additionally adjusted by the BP level (P values below 0.033) Conclusions: Among office and ambulatory BP monitoring measures, higher short-term variability in the 24-h and nighttime systolic BP was associated with lower cognitive function and dementia independent of the BP level. This is the first epidemiological study showing an association between short-term BP variability and dementia. Future longitudinal studies need to address whether short-term BP variability could be a potential marker for cognitive decline and might help in assessing the risk of dementia.

Propofol enhancement of slow wave sleep to target the nexus of geriatric depression and cognitive dysfunction: protocol for a phase I open label trial

IntroductionLate-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow...

The Influence of Personality Type D and Coping Strategies on Cognitive Functioning in Students.

Academic and emotional challenges faced by medical students can affect their psychological well-being and health. Personal characteristics may also predispose one to the manifestation of distress reactions. Individuals with type D personality have an increased tendency to develop depressive reactions and somatic diseases, including the presence of cognitive dysfunction. In students, the presence of cognitive dysfunction may additionally adversely affect academic and psycho-emotional problems. The purpose of this study was to examine the influence of type D personality and coping strategies on cognitive functioning in medical students. A cross-sectional study included 258 medical students (age 19 ± 1.2 years, 79 men). All participants completed psychological questionnaires (DS-14 to identify type D personality, and The Coping Strategy Indication, CSI-to determine coping strategies), as well as extensive neuropsychological testing of cognitive functions. Among the medical students examined, the frequency of identification of type D personality was 44%. In persons with personality type D, according to psychometric testing, a decrease in the level of functional mobility of nervous processes (FMNP) was noted, which was manifested in an increase in the test completion time (p < 0.001) and an increase in the number of errors (p < 0.001) during the FMNP test, and an increase in the test completion time in the attention concentration test. In addition, in type D participants, an increase in the test execution time during the attention test was noted (p = 0.007). Personality type D was an independent risk factor for cognitive decline in students in multiple linear regression analysis, when type D was analyzed as a dichotomous construct. Assessing personal characteristics and identifying personality type D is advisable for medical students, to develop subsequent programs to increase their resistance to academic challenges, improve cognitive function, and also to prepare for future stress loads during professional activities in the field of healthcare.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline.

With the rapidly aging human population, age-related cognitive decline and dementia are becoming increasingly prevalent worldwide. Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota, microbial metabolites, and the functions of astrocytes. The microbiota-gut-brain axis has been the focus of multiple studies and is closely associated with cognitive function. This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases. This article also summarizes the gut microbiota components that affect astrocyte function, mainly through the vagus nerve, immune responses, circadian rhythms, and microbial metabolites. Finally, this article summarizes the mechanism by which the gut microbiota-astrocyte axis plays a role in Alzheimer's and Parkinson's diseases. Our findings have revealed the critical role of the microbiota-astrocyte axis in age-related cognitive decline, aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice.

Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.

Effects of xylo-oligosaccharide on gut microbiota, brain protein expression, and lipid profile induced by high-fat diet

Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Risk Factors for Cognitive Impairment in Multiple Sclerosis Patients

Cognitive impairment is one of the most significant burdens among the many neurological complaints in multiple sclerosis patients. Cognitive deficits negatively impact these patients’ quality of life, leading to partial or total loss of several mental functions, such as learning, memory, perception, or problem-solving. While the precise mechanisms involved in the onset and evolution of cognitive decline remain unknown, several risk factors have been associated with intellectual disability. With increasing data on this topic in recent years, the main aim of this review is to summarize the most relevant risk factors correlated with cognitive impairment in multiple sclerosis patients. Firstly, the authors demonstrate the importance of mental disability based on epidemiological data from multiple sclerosis patient cohorts. Subsequently, the intensely debated major risk factors for cognitive decline are discussed, with brief insights into the pathophysiology and possible underlying mechanisms. Finally, the authors describe the impact of medication on cognitive impairment in multiple sclerosis patients, highlighting the main research directions for future studies.