Risk Of Cognitive Impairment Research Articles

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}]=0.44 [0.26, 0.76], p=0.003) and executive function (adjusted HR [95% CI]=0.60 [0.37, 0.97], p=0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

Associations between structural neuroimaging markers of Alzheimer's risk and scam susceptibility.

Older adults with greater scam susceptibility are at greater risk for mild cognitive impairment and incident Alzheimer's dementia, regardless of baseline cognition. This, combined with documented associations between scam susceptibility and beta amyloid at death suggests that scam susceptibility may be an earlier indicator of pathological aging than cognition. Little, however, is known about whether in vivo neuroimaging markers of early-stage risk for Alzheimer's dementia are also related to scam susceptibility; such knowledge will inform upon the associations of neurodegenerative processes with scam susceptibility and may help identify vulnerable individuals. Participants were 472 community-based adults without dementia (age ~ 81y; 75% women) from the Rush Memory and Aging Project. Baseline 3T MRI T1-weighted structural and T2-weighted FLAIR data were used to assess the cortical thickness 'signature' of Alzheimer's disease (AD-CT) and white matter hyperintensity (WMH) burden, respectively. Scam susceptibility was measured using a questionnaire that assessed behaviors associated with vulnerability to fraud and scams. Demographically-adjusted linear effects regression models determined the relationship of each neuroimaging measure, first separately and then combined, with scam susceptibility. Reduced AD-CT was associated with higher levels of scam susceptibility (estimate=-0.10, standard error = 0.03, p = 0.002). WMH burden was not associated with scam susceptibility either alone or when combined in the same model as AD-CT (p-values ≥ 0.14). Results for AD-CT persisted after the inclusion of WMH burden. AD-CT was associated with scam susceptibility in older adults without dementia possibly signaling an in vivo profile of this behavior.

Circulating IL-17A and Executive Function in Middle-Aged Adults with and without Type 2 Diabetes

Abstract Background Midlife cardiovascular risk factors, such as Type 2 Diabetes Mellitus (T2DM) and obesity, are associated with a greater risk of cognitive impairment and dementia in later life, with altered peripheral inflammation postulated as a crucial mechanistic link. Yet there is a significant gap in knowledge regarding when pathogenic alterations to these systemic inflammatory responses change during the early stages of cognitive dysfunction prior to overt disease development. To assess the earliest possible signs of this link, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Methods A comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. A panel of ten serum chemokines and cytokines were measured at both time-points using high-sensitivity assays (Eotaxin, MCP-1, MIP-1β, CXCL-10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α). Results Overall, 136 individuals were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ by T2DM status. Yet on cross-sectional analyses, we observed consistent evidence across timepoints between greater circulating IL-17A and poorer performance on tests of executive function/attention (β: -0.21; -0.40, -0.02, p = 0.03 at baseline; β: -0.26; -0.46, -0.05, p = 0.02 at follow-up) as well as poorer reaction time (β: 0.34; 0.12, 0.56, p = 0.003 at follow-up). These persisted on covariate adjustment and did not differ by T2DM status. Conclusion We provide exploratory evidence that greater serum IL-17A levels are associated with poorer executive function in midlife. Long-term follow-up of this and other cohorts will further elucidate this relationship to provide further mechanistic insights and potentially identify individuals at greatest risk for later cognitive decline.

Spatiotemporal Gait Characteristics and Neuropsychological Performance in Midlife

Abstract Background Midlife risk factors such as Type 2 Diabetes Mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life, with executive function, memory and attention domains often affected first. Spatiotemporal gait characteristics are increasingly recognised as biomarkers of neurocognitive function and later dementia risk. Methods Using an automated walkway, 24 spatiotemporal gait parameters were examined across 5 domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions. Neurocognitive function was measured using a neuropsychological assessment battery. Linear regression was used assess the relationship between each gait parameter across the three walks and cognitive function. Results 102 middle-aged adults underwent assessment, 65 with uncomplicated T2DM (57.5 ± 8.0 years; 40% female) and 37 healthy controls (57.0 ± 8.3 years; 62.1% female). T2DM was associated with significant changes in gait phases and rhythm domains at usual-pace, and greater gait variability observed during maximal-pace and dual-task. In the overall cohort, both gait pace and rhythm domains were associated with memory and executive function during usual pace walking. At maximal-pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual-task, associations between gait variability and delayed memory and executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Conclusion This supports the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals. Discrete associations were seen between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms, in addition to single-task usual-pace gait, may be important in cognitively unimpaired populations with risk factors for later cognitive decline - with the aim of identifying individuals who may benefit most from potential preventative interventions.

Prediction and validation of mild cognitive impairment in occupational dust exposure population based on machine learning

ObjectiveWorkers exposed to dust for extended periods may experience varying degrees of cognitive impairment. However, limited research exists on the associated risk factors. This study aims to identify key variables using machine learning algorithms (ML) and develop a model to predict the occurrence of mild cognitive impairment in miners. Methods: A total of 1938 miners were included in the study. Univariate analysis and multivariable logistic regression were employed to identify independent risk factors for cognitive impairment among miners. The dataset was randomly divided into a training set and a validation set in an 8:2 ratio of 1550 and 388 individuals, respectively. An additional group of 351 miners was collected as a test set for cognitive impairment assessment. Seven machine learning algorithms, including XGBoost, Logistic Regression, Random Forest, Complement Naive Bayes, Multi-layer Perceptron, Support Vector Machine, and K-Nearest Neighbors, were used to establish a predictive model for mild cognitive impairment in the dust-exposed population, based on baseline characteristics of the workers. The predictive performance of the models was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUC), and the XGBoost model was further explained using the Shapley Additive exPlanations (SHAP) package. Cognitive function assessments using rank sum tests were conducted to compare differences in cognitive domains between the mild cognitive impairment group and the normal group. Results: Univariate and multivariable logistic regression analyses revealed that education level, Age, Work years, SSRS (Self-Rating Scale for Stress), and HAMA (Hamilton Anxiety Rating Scale) were independent risk factors for cognitive impairment among dust-exposed workers. Comparative analysis of the performance of the seven machine learning algorithms demonstrated that XGBoost (training set: AUC=0.959, validation set: AUC=0.795) and Logistic Regression (training set: AUC=0.818, validation set: AUC=0.816) models exhibited superior predictive performance. Results from the test set showed that the AUC of the XGBoost model (AUC=0.913) outperformed the Logistic Regression model (AUC=0.778). Miners with mild cognitive impairment exhibited significant impairments (p<0.05) in visual-spatial abilities, attention, abstract thinking, and memory areas. Conclusion: Machine learning algorithms can predict the risk of cognitive impairment in this population, with the XGBoost algorithm showing the best performance. The developed model can guide the implementation of appropriate preventive measures for dust-exposed workers.

Glyoxalase 1 overexpression improves neurovascular coupling and limits development of mild cognitive impairment in a mouse model of type 1 diabetes.

Diabetes is associated with cognitive impairment, but the underlying mechanism remains unclear. Methylglyoxal (MGO), a precursor to advanced glycation endproducts (AGEs), is elevated in diabetes and linked to microvascular dysfunction. In this study, overexpression of the MGO-detoxifying enzyme glyoxalase 1 (Glo1) was used in a mouse model of diabetes to explore whether MGO accumulation in diabetes causes cognitive impairment. Diabetes was induced with streptozotocin. Fasting blood glucose, cognitive function, cerebral blood flow, neurovascular coupling (NVC), Glo1 activity, MGO and AGEs were assessed. In diabetes, MGO-derived hydroimidazolone-1 increased in the cortex, and was decreased in Glo1-overexpressing mice compared to controls. Visuospatial memory was decreased in diabetes, but not in Glo1/diabetes. NVC response time was slightly increased in diabetes, and normalised in the Glo1-overexpressing group. No impact of diabetes or Glo1 overexpression on blood-brain barrier integrity or vascular density was observed. Diabetes induced a mild visuospatial memory impairment and slightly reduced NVC response speed and these effects were mitigated by Glo1. This study shows a link between MGO-related AGE accumulation and cerebrovascular/cognitive functions in diabetes. Modulation of the MGO-Glo1 pathway may be a novel intervention strategy in patients with diabetes who have cerebrovascular complications. KEY POINTS: Diabetes is associated with an increased risk of stroke, cognitive decline, depression and Alzheimer's disease, but the underlying mechanism remains unclear. Methylglyoxal (MGO), a highly reactive by-product of glycolysis, plays an important role in the development of diabetes-associated microvascular dysfunction in the periphery and is detoxified by the enzyme glyoxalase 1. Diabetes reduced visuospatial memory in mice and slowed the neurovascular coupling response speed, which was improved by overexpression of glyoxalase 1. MGO formation and MGO-derived advanced glycation endproduct (AGE) accumulation in the brain of diabetic mice are associated with a slight reduction in neurovascular coupling and mild cognitive impairment. The endogenous formation of MGO, and the accumulation of MGO-derived AGEs, might be a potential target in reducing the risk of vascular cognitive impairment in people with diabetes.

Association of Seizure Control With Cognition in People With Normal Cognition and Mild Cognitive Impairment.

Seizures are common in dementia and associated with accelerated cognitive decline. However, the impact of active vs remote seizures on cognition remains understudied. This study aimed to investigate the impact of active vs remote seizures on cognition in people with normal cognition and mild cognitive impairment (MCI). This longitudinal, multicenter cohort is based on National Alzheimer's Coordinating Center data of participants recruited from 39 Alzheimer's Disease Centers in the United States from September 2005 to December 2021. All participants with normal cognition and MCI and at least 2 visits were included. Primary outcome, that is, cognitive decline, was determined using Clinical Dementia Rating (CDR) from (1) normal-to-impaired (CDR ≥0.5) and (2) MCI-to-dementia (CDR ≥1) groups. The effect of active seizures (over the preceding 12 months), remote seizures (previous seizures but none over the preceding 12 months), and no seizures (controls) on cognition was assessed. Subgroups of chronic seizures at enrollment and new-onset seizures were further analyzed. Cox regression models assessed the risk of all-cause MCI and/or dementia. All models were adjusted for age, sex, education, race, hypertension, and diabetes. Of the 13,726 participants with normal cognition at enrollment (9,002 [66%] female; median age 71 years), 118 had active seizures and 226 had remote seizures. Of the 11,372 participants with MCI at enrollment (5,605 [49%] female; median age 73 years), 197 had active seizures and 226 had remote seizures. Active seizures were associated with 2.1 times higher risk of cognitive impairment (adjusted hazard ratio [aHR] 2.13, 95% CI 1.60-2.84, p < 0.001) in cognitively healthy adults (median years to decline: active seizures = ∼1, remote seizures = ∼3, no seizures = ∼3) and 1.6 times higher risk of dementia (aHR 1.58, 95% CI 1.24-2.01, p < 0.001) in those with MCI (median years to decline: active seizures = ∼1, remote seizures = ∼2, controls = ∼2). This risk was not observed with remote seizures. In this study, active seizures but not remote seizures were associated with earlier cognitive decline in both cognitively normal adults and those with MCI, independent of other dementia risk factors. Therefore, early identification and management of seizures may present a path to mitigation of cognitive decline in the aging epileptic population. A limitation is that causality cannot be confirmed in our observational longitudinal study.

Clinical utility of brief screening measures during neuropsychological consultation for pediatric onset multiple sclerosis.

Pediatric-onset multiple sclerosis (POMS) accounts for approximately 2 to 5% of all individuals with MS and is associated with an increased risk for cognitive impairment. In recent years, neuropsychological screening questionnaires have been increasingly utilized for pediatric populations in multidisciplinary settings. This study examines the clinical utility of the Colorado Learning Difficulties Questionnaire (CLDQ) and Pediatric Perceived Cognitive Functioning (Peds PCF) screening measures for identifying cognitive impairment in persons with POMS during a target neuropsychological evaluation. Retrospective data was gathered from electronic medical records at a single pediatric hospital. Forty-nine participants were included (69% female; 43% Hispanic/Latinx; mean age = 16.1 years old, range = 9.9 to 20.6 years old). Correlation analyses demonstrated strong interrelatedness between caregiver ratings on screening measures and performance on traditional neuropsychological measures. Effect sizes were medium across comparisons (CLDQ: Spearman's rho = -.321 to -.563; PedsPCF: Spearman's rho = .308 to .444). Exploratory cut-points using receiver operating characteristic analysis and Youden indices are also discussed. Comparison of scores across caregiver rating questionnaires and on a targeted neuropsychological battery suggests that the screening surveys alone may not be sensitive enough to identify children with cognitive impairments, but ratings may provide qualitatively meaningful information along with neuropsychological testing. This study illustrates how pediatric neuropsychologists can leverage screening tools to focus consultative interviews and effectively triage referrals for evaluation within an academic medical setting.

Relationships between Serum Lipid, Uric Acid Levels and Mild Cognitive Impairment in Parkinson's Disease and Multiple System Atrophy.

Mild cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD) and multiple system atrophy (MSA). Few studies have previously been conducted on the correlation between serum uric acid (SUA) and lipid levels and mild cognitive impairment in PD and MSA. Participants included 149 patients with PD and 99 patients with MSA. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Evaluations were conducted on SUA and lipid levels, which included triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC). Patients with PD and MSA diagnosed with mild cognitive impairment demonstrated multiple cognitive domain impairment when compared with patients with normal cognition. Attentional impairment was more pronounced in patients with MSA when compared with PD (p = 0.001). In PD, the risk of mild cognitive impairment was lower in the highest quartiles and secondary quartile of SUA than in the lowest quartiles (odds ratio [OR] = 0.281, 95% confidence intervals [CI]: 0.097-0.810, p = 0.019; and OR = 0.317, 95% CI: 0.110-0.911, p = 0.033). In MSA, the risk of mild cognitive impairment was lower in the third and highest quartile of SUA than in the lowest quartile (OR = 0.233, 95% CI: 0.063-0.868, p = 0.030; and OR = 0.218, 95% CI: 0.058-0.816, p = 0.024). In patients with PD, the MoCA scores were negatively correlated with TC levels (r = -0.226, p = 0.006) and positively correlated with SUA levels (r = 0.206, p = 0.012). In MSA, the MoCA scores were positively correlated with SUA levels (r = 0.353, p = 0.001). Lower SUA levels and higher TC levels are a possible risk factor for the risk and severity of mild cognitive impairment in PD. Lower SUA levels are a possible risk factor for the risk and severity of mild cognitive impairment in MSA.

Association between widowhood and cognitive function among Chinese older adults with hearing impairment: the moderating effect of social support and participation

BackgroundOlder adults with hearing impairments are vulnerable to cognitive impairment. Although previous reports suggest a correlation between widowhood and cognitive impairment, further investigation is needed to elucidate the effect of widowhood on cognitive function and the moderating effects of social support and participation on widowhood-related cognitive impairment in this vulnerable demographic.MethodsThe study’s data were sourced from the nationally representative Chinese Longitudinal Healthy Longevity Survey (CLHLS) for the years 2011, 2014, and 2018. Multiple linear regression was used to analyze the association between widowhood and cognitive function among older adults. Multivariate logistic regression examined the effect of widowhood on the likelihood of experiencing various levels of cognitive impairment in older adults with hearing impairments. A moderating effect model explored the roles of social support and participation in mitigating widowhood-related cognitive impairment.ResultsThe cognitive function of older adults with hearing impairment was found to be lower than that of those without hearing impairment. Widowhood was significantly negatively correlated with Mini-Mental State Examination (MMSE) scores in older adults, both with (Coef. = -0.898) and without (Coef.: = -0.680) hearing impairments. A stronger association was observed between widowhood and declining cognitive function among older adults with hearing impairment. Specifically, widowhood may be more likely to significantly increase the likelihood of moderate and severe cognitive impairment (RRR = 1.326, 1.538) among older adults with hearing impairments. Social support and social participation significantly moderated the cognitive impairment associated with widowhood among hearing-impaired older adults. These forms of support and engagement are buffers against the risk of widowhood-related cognitive impairment among this demographic.ConclusionsOur findings indicate that widowhood is significantly associated with cognitive impairment in older adults with hearing impairment. Social support and participation help mitigate this risk. Strategies should prioritize early screening, specialized cognitive rehabilitation, comprehensive care, and enhancing social support and participation to maintain cognitive health in this vulnerable population following widowhood.

Predicting Adherence to Computer-Based Cognitive Training Programs Among Older Adults: Study of Domain Adaptation and Deep Learning.

Cognitive impairment and dementia pose a significant challenge to the aging population, impacting the well-being, quality of life, and autonomy of affected individuals. As the population ages, this will place enormous strain on health care and economic systems. While computerized cognitive training programs have demonstrated some promise in addressing cognitive decline, adherence to these interventions can be challenging. The objective of this study is to improve the accuracy of predicting adherence lapses to ultimately develop tailored adherence support systems to promote engagement with cognitive training among older adults. Data from 2 previously conducted cognitive training intervention studies were used to forecast adherence levels among older participants. Deep convolutional neural networks were used to leverage their feature learning capabilities and predict adherence patterns based on past behavior. Domain adaptation (DA) was used to address the challenge of limited training data for each participant, by using data from other participants with similar playing patterns. Time series data were converted into image format using Gramian angular fields, to facilitate clustering of participants during DA. To the best of our knowledge, this is the first effort to use DA techniques to predict older adults' daily adherence to cognitive training programs. Our results demonstrated the promise and potential of deep neural networks and DA for predicting adherence lapses. In all 3 studies, using 2 independent datasets, DA consistently produced the best accuracy values. Our findings highlight that deep learning and DA techniques can aid in the development of adherence support systems for computerized cognitive training, as well as for other interventions aimed at improving health, cognition, and well-being. These techniques can improve engagement and maximize the benefits of such interventions, ultimately enhancing the quality of life of individuals at risk for cognitive impairments. This research informs the development of more effective interventions, benefiting individuals and society by improving conditions associated with aging.

Joint Association of Combined Healthy Lifestyle Factors and Hearing Loss With Cognitive Impairment in China.

Hearing loss and lifestyle factors have been associated with cognitive impairment. We aimed to explore the joint association of combined healthy lifestyle factors and hearing loss with cognitive impairment, which has been scarcely studied. This baseline study used data from the CHOICE-Cohort study (Chinese Hearing Solution for Improvement of Cognition in Elders). Hearing loss was assessed by the better-ear pure-tone average. A composite healthy lifestyle score was built based on never smoking, never drinking, regular physical activity, and a balanced diet. Cognitive impairment was diagnosed by the Mini-Mental State Examination score of less than 24. We included 17057 participants aged 60 years or older in China (mean age 69.8 [standard deviation 6.2] years, 55.7% female). Among the participants, 48.3% (n = 8 234) had mild hearing loss, and 25.8% (n = 4 395) had moderate or greater hearing loss. The proportion of participants with healthy lifestyle scores of 0-1, 2, 3, and 4 was 14.9% (n = 2 539), 29.3% (n = 5 000), 37.4% (n = 6 386), and 18.4% (n = 3 132), respectively. About 29.6% (n = 5 057) participants had cognitive impairment. When compared to those with normal hearing and healthy lifestyle (scores of 3-4), participants with hearing loss plus unhealthy lifestyle (scores of 0-2) exhibited approximately twofold increased risk of cognitive impairment (odds ratio [OR] = 1.92, 95% confidence interval [CI] 1.70-2.18). Conversely, the risk was greatly attenuated by adherence to healthy lifestyle in individuals with hearing loss (OR = 1.57, 95% CI 1.40-1.76). Our findings demonstrated adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of cognitive impairment among participants with hearing loss.

The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging.

Aging is closely associated with various cerebrovascular pathologies that significantly impact brain function, with cerebral small vessel disease (CSVD) being a major contributor to cognitive decline in the elderly. Consequences of CSVD include cerebral microhemorrhages (CMH), which are small intracerebral bleeds resulting from the rupture of microvessels. CMHs are prevalent in aging populations, affecting approximately 50% of individuals over 80, and are linked to increased risks of vascular cognitive impairment and dementia (VCID). Hypertension is a primary risk factor for CMHs. Vascular smooth muscle cells (VSMCs) adapt to hypertension by undergoing hypertrophy and producing extracellular matrix (ECM) components, which reinforce vessel walls. Myogenic autoregulation, which involves pressure-induced constriction, helps prevent excessive pressure from damaging the vulnerable microvasculature. However, aging impairs these adaptive mechanisms, weakening vessel walls and increasing susceptibility to damage. Insulin-like Growth Factor 1 (IGF-1) is crucial for vascular health, promoting VSMC hypertrophy, ECM production, and maintaining normal myogenic protection. IGF-1 also prevents microvascular senescence, reduces reactive oxygen species (ROS) production, and regulates matrix metalloproteinase (MMP) activity, which is vital for ECM remodeling and stabilization. IGF-1 deficiency, common in aging, compromises these protective mechanisms, increasing the risk of CMHs. This review explores the vasoprotective role of IGF-1 signaling in the cerebral microcirculation and its implications for preventing hypertension-induced CMHs in aging. Understanding and addressing the decline in IGF-1 signaling with age are crucial for maintaining cerebrovascular health and preventing hypertension-related vascular injuries in the aging population.

B - 109 Long-Term Cognitive Effects of Combined Opioid/Non-Opioid Use

Abstract Objective Chronic pain is estimated to afflict 25–50% of community-dwelling older adults (Cravello et al., 2019). Despite the growing epidemic, opioids remain commonly prescribed analgesics, and approximately 10% of older adults with intermittent opioid use become chronic users (Ramachandran et al., 2021). This is concerning given an observed association between cognitive decline and prescription opioid use within this population (Warner et al., 2022). In efforts to reduce opioid consumption, opioid/non-opioid combinations have been used (Pergolizzi et al., 2023); however, the long-term cognitive impact of such alternatives has not been investigated. Thus, the current case report investigates the neurocognitive outcome following longtime opioid/non-opioid combination cessation in the context of chronic pain. Method A 69-year-old Black woman with approximate 30-year history of chronic pain underwent neuropsychological re-evaluation 2 years post-initial assessment and 1.5 years after stopping combined hydromorphone/clonidine use via intrathecal pump. Baseline MRI brain revealed mild diffuse atrophy and punctate nonspecific T2 white matter hyperintensities. CT head approximately 1 year later was unremarkable. Results Neuropsychological re-assessment approximately 2 years post-baseline evaluation revealed significantly declined performances on speed-mediated tasks (e.g., oral numeric sequencing, fluency) amid an otherwise grossly stable, albeit globally impaired, cognitive profile. Conclusions This study elucidates the impact of a 1.5-year period of abstinence from 13 years of combined intrathecal opioid/non-opioid use. Overall, results suggest that cognitive performance, even following this abstinence period, is not improved. Thus, while opioid/non-opioid therapies may reduce opioid exposure, deleterious cognitive effects persist. This study highlights the importance of non-opioid analgesics in efforts to attenuate cognitive impairment risk.

Association of dietary diversity and weight change with cognitive impairment among Chinese elderly: A prospective national cohort study

BackgroundDietary diversity is reported to be beneficial for cognitive function, while the effect may be offset by weight change status. We aimed to examine the association of dietary diversity and weight change with cognitive impairment among older adults. MethodsWe used three waves from 2008 to 2014 of the Chinese Longitudinal Survey of Health and Longevity, which included 16,954 participants for the subsequent screening and analysis. Dietary diversity information was collected from the food frequency questionnaire. Cognitive function was assessed using the Mini Mental State Examination. The relation of dietary diversity and weight change with cognitive impairment was investigated using Cox proportional hazards models and cubic spline regression. ResultsCompared with those reported poor dietary diversity at baseline, participants with good dietary diversity had a 16 % (hazard ratio [HR] = 0.84, 95 % confidence interval [CI]: 0.71–0.99) lower risk of cognitive impairment. The HR and 95 % CI of participants with consistently good dietary diversity from 2008 to 2011 was 0.71 (0.57–0.89) for cognitive impairment compared to those with consistently poor dietary diversity. Compared with the weight stable group, the HRs and 95 % CI for cognitive impairment were 1.34 (1.10–1.64) in weight loss group, and 1.08 (0.88–1.33) in weight gain group. Restricted cubic splines showed the risk of cognitive impairment decreased with higher dietary diversity score or less weight change, though no significant interaction between dietary diversity and weight change was found. LimitationGiven the observational nature of this study, there might be a reverse causation for the observed association. ConclusionEstablishing and maintaining good dietary diversity were associated with a lower risk of cognitive impairment regardless of weight change status, whereas weight loss was associated with increased cognitive impairment risk independently among older Chinese adults.

Rehabilitation Impact of Vivifrail Exercise Program Type C on the Cognitive Function of Pre-Frail Elderly People in the Community

Highlights:1. This study emphasizes the importance of providing physical exercises to pre-frail elderly individuals, especially in a community setting.2. This study establishes a foundation for future research to explore the relationship between physical exercise, particularly the Vivifrail Type C Protocol, and cognitive function in pre-frail elderly individuals. Abstract Frailty is a clinical syndrome that increases vulnerability, potentially leading to disability or death. The pre-frail phase is ideal for preventing frailty and improving quality-adjusted life years, particularly through physical exercises that reduce the risk of dementia and cognitive impairment. Multicomponent exercises, such as the Vivifrail Exercise Program, may enhance cognitive function and daily independence by preventing and mitigating frailty through tailored routines. However, its impact on cognitive function in pre-frail elderly people had not been well studied. This study aimed to determine the effect of the Vivifrail Exercise Program Type C on the cognitive function of pre-frail elderly people. This study was a quasi-experiment with a non-randomized control group pretest-posttest design. The sample was chosen by the quota sampling method. Twenty-seven subjects were analyzed, comprising 16 individuals in the exercise group and 11 individuals in the control group. The exercise group participated in the Vivivfrail Type C Exercise Program, with 45-minute sessions conducted biweekly for 12 weeks. The evaluated parameters included the Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) and the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA). The statistical analysis utilized the Kruskal-Wallis test, followed by the post-hoc Mann-Whitney test and independent t-test (p&lt;0.05). A path analysis was performed using simple linear regression. The subjects' average ages were 72.2 years in the control group and 67.47 years in the exercise group. The Vivifrail Exercises Program Type C significantly improved the MoCA-INA scores from 20.25 to 24.06. It also increased the LOTCA scores in several domains, i.e., thinking operations and visual perception. The exercise group demonstrated more improvement than the control group (p=0.032). An enhancement in cognitive function was particularly observed in elderly women with pre-frailty. In conclusion, the Vivifrail Exercise Program Type C can help improve the cognitive function of the elderly within the community.

Tooth Loss in Periodontitis Patients-A Risk Factor for Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

Periodontal disease and tooth loss have been long suggested as risk factors of mild cognitive impairment. The underlying mechanisms could be systemic chronic inflammatory mediators, direct pathologic challenge to the nervous system, malnutrition and/or loss of neurosensory stimulation input causing brain atrophy. This review aimed to examine the existing literature studies linking the effect of periodontal disease and tooth loss on the development of mild cognitive impairment. A systematic review using PEO was conducted. Three electronic databases, namely Embase, Medline and DOSS (UCLan), were searched for relevant articles published up to April 2023. Google Scholar and a hand search were also conducted to ensure no relevant studies had been missed. The Newcastle-Ottawa scale was used to assess the quality of studies. The findings showed that chronic periodontitis and tooth loss, both individually and in combination, led to an increased risk of mild cognitive decline in adults over 50 years. Within the limitations of this review, periodontitis and tooth loss both contribute to an increased risk of mild cognitive impairment and dementia, but the evidence so far is not strong. In future, more robustly designed studies investigating periodontal disease and tooth losslink with cognitive health decline are required with a longer follow-up duration.

Apolipoprotein E4 and Alzheimer's disease causality under adverse environments and potential intervention by senolytic nutrients

Apolipoprotein E (apoE) has a pivotal role in Alzheimer's Disease (AD) pathophysiology. APOE4 has been recognized as a risk factor for developing late-onset AD. Recently, APOE4 homozygosity was regarded as a new familial genetic trait of AD. In this opinion paper, we summarized the potential pleiotropic antagonism role of APOE4 in children living under early life adversity and afflicted with enteric infection/malnutrition-related pathogenic exposome. APOE4 was found to be neuroprotective early in life despite its increasing risk for AD with aging. We call for awareness of the potential burden this can bring to the public health system when APOE4 carriers, raised under adverse environmental conditions in early life and then aging with unhealthy lifestyles in later life may be at special risk for cognitive impairments and acquired AD. We postulate the importance of anti-senescence therapies to protect these individuals and remediate aging-related chronic illnesses.

Hippocampal volume maximally modulates the relationship between subsyndromal symptomatic depression and cognitive impairment in non-demented older adults

BackgroundSubsyndromal symptomatic depression (SSD) is associated with an elevated risk of cognitive impairment in non-demented older adults. Given that hippocampal and middle temporal gyrus atrophy have been shown to cause SSD, our study aimed to investigate the effect of hippocampal volume on the association between SSD and cognitive impairment. Methods338 non-demented older adults from the ADNI (Alzheimer's Disease Neuroimaging Initiative) cohort who underwent cognitive assessments, questionnaires on depressive symptoms and MRI brain were studied. SSD group is defined as a score of 1–5 based on Geriatric Depression Scale scores. We conducted causal mediation analyses to investigate the effect of hippocampal volume on cognitive performance cross-sectionally. ResultsThe SSD group displayed lower left and right hippocampal volume (p<0.01) than the non-SSD group. SSD was linked to poorer cognition and smaller hippocampal volume. We found that hippocampal volume partially mediated the effect of SSD on cognitive performance including the global cognition and the cognitive section of Alzheimer's Disease Assessment Scale, with mediation percentages ranging from 6.45 % to 30.46 %. In addition, we found that the thickness of the left middle temporal, right entorhinal and right fusiform gyrus, brain regions linked to AD, mediate the relationship between SSD and cognition with mediation percentages ranging from 8.67 % to 21.44 %. LimitationsOur article didn't differentiate between mild cognitive impairment and normal population. ConclusionThe associations of SSD and cognitive impairment are linked to alterations in Alzheimer's Disease related brain regions.

Sarcopenia and cognitive impairment in older adults: Long-term prognostic implications based on the National Health and Nutrition Examination Survey (2011–2014)

AimsThe relationship between sarcopenia and cognitive impairment in older adults remains contentious. This study investigates this association and examines the long-term prognosis for individuals with both conditions. MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, this study focuses on the correlation between sarcopenia and cognitive impairment, as well as the extended prognosis for individuals managing these conditions. ResultsThe study cohort comprised 2890 participants, with 648 (22.4 %) diagnosed with sarcopenia. Multivariable logistic regression analysis identified a significant association between sarcopenia and an increased risk of cognitive impairment (adjusted odds ratio [aOR]: 1.68, 95 % confidence interval [CI]: 1.30–2.17). Over a median follow-up period of 48 months, 200 individuals (6.9 %) succumbed to cardiovascular and cerebrovascular diseases (CCVDs), including hypertension, congestive heart failure, coronary artery disease, and stroke, as well as Alzheimer's disease (AD). Participants had comorbid conditions such as CCVDs and diabetes mellitus. Kaplan–Meier survival analysis and the Cox proportional hazards model indicated that individuals with both sarcopenia and cognitive impairment had the highest mortality risk from CCVDs and AD (adjusted hazard ratio [aHR]: 2.73, 95 % CI: 1.48–5.02). Individuals with sarcopenia and comorbidities exhibited a higher mortality risk from CCVDs or AD compared to those without sarcopenia but with comorbidities (aHR: 2.71, 95 % CI: 1.37–5.37). ConclusionSarcopenia is independently associated with cognitive impairment. Older adults with both sarcopenia and cognitive impairment or concurrent comorbidities face increased mortality risks from CCVDs or AD compared to their healthy counterparts. Clinical implication•Sarcopenia is associated with cognitive impairment.•Cognitive impairment and comorbidities increased the risk of mortality from CCVDs and AD for sarcopenia patients.