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Previous studies identified individual-level socioeconomic factors as key determinants of cognitive health. This study investigated the effect of area-based socioeconomic deprivation on cognitive outcomes in midlife to early late-life New Zealanders without cognitive impairment at baseline. Data stemmed from a subsample of the New Zealand Health, Work and Retirement Study, a cohort study on ageing, who completed face-to-face interviews and were reassessed two years later. Cognitive functioning was measured using Addenbrooke's Cognitive Examination-Revised, adapted for culturally acceptable use in Aotearoa New Zealand. Area-based socioeconomic deprivation was assessed using the New Zealand Deprivation Index (NZDep2006). Linear mixed-effects models analysed the association between area-based socioeconomic deprivation and cognitive outcomes. The analysis included 783 participants without cognitive impairment at baseline (54.7% female, mean age 62.7 years, 25.0% Māori, the Indigenous people of Aotearoa New Zealand). There was an association between higher area-based socioeconomic deprivation and lower cognitive functioning (B = -0.08, 95%CI: -0.15;-0.01; p = .050) and cognitive decline (B = -0.12, 95%CI: -0.20;-0.04, p = .013) over two years, while controlling for covariates. The findings emphasise the importance of considering neighbourhood characteristics and broader socioeconomic factors in strategies aimed at mitigating cognitive health disparities and reducing the impact of dementia in disadvantaged communities., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Few studies have considered nutrients as a mixture and their impact on Mild Cognitive Impairment (MCI). The generalized linear regression (GLM), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models are fitted to estimate the association between intake of a mixture of nutrients and MCI. Comparing the results from these three models, vitamin E and vitamin B6 were identified as the most important factors associated with the risk of MCI. Considering the characteristics of BKMR, it may be more advantageous to use BKMR to estimate the combined the joint effects of nutrients mixture. In the future, studies need to move from a "one nutrient at a time" approach to simultaneous analyses of multiple nutrients intakes in order to understand and quantify the joint effect of nutrients mixture on health., (© 2024. The Author(s).)

Asthma and cognitive dysfunction represent significant public health challenges. Our study aimed to investigate the relationship between asthma and cognitive dysfunction in adults aged ≥ 60 years, and explore the role of systemic immune inflammation index (SII) in asthma - cognitive dysfunction link. The retrospective cross-sectional study included 2,579 participants aged ≥ 60 years from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) cycles. Asthma diagnosis was confirmed using the MCQ010 questionnaire, cognitive function assessed through the Digit Symbol Substitution Test (DSST). SII was calculated using the formula: (platelet count × neutrophil count)/lymphocyte count. Controlling for demographic variables including sex, age, race and/ethnicity, poverty-to-income ratio (PIR) and education level, a negative association was found between asthma and DSST scores (β = -1.75, 95% CI: -3.38, -0.120, P = 0.037). This association persisted even after further adjustments for body mass index (BMI) and diabetes (β = -1.72, 95% CI: -3.38, -0.057, P = 0.043). Moreover, subgroup analysis showed no significant association of sex, age, race/ethnicity, BMI or diabetes with the relationship between asthma and cognitive function. Mediation analysis indicated SII was a mediator of asthma-induced cognitive impairment, a notable Average Causal Mediated Effect (ACME) (P = 0.004) between SII and cognitive dysfunction. Our investigation indicated that elderly asthma (aged ≥ 60 years) was predisposed to cognitive dysfunction, independent of sex, age, race/ethnicity, BMI and diabetes. Furthermore, mediation analysis suggested that asthma might contribute to cognitive dysfunction through the involvement of SII., (© 2024. The Author(s).)

Research on socioeconomic position (SEP) and mild neurocognitive impairment, considered a transient state between normal cognitive function and dementia is limited. The purpose of this study was to determine the role of SEP in transitioning between different cognitive states and mortality risk. Using nationally representative English data and utilising a multistate model association between SEP and the risk of transitioning from no cognitive impairment (NOCI) to Cognitive impairment no dementia (CIND), dementia and death were investigated. The potential reverse transition from CIND to NOCI was also explored. The probabilities of transitioning between cognitive states and time spent in each state differed significantly between those with lower and higher levels of SEP. Higher wealth was associated with a reverse transition from CIND to NOCI [HR = 1.56, CI (1.42,1.72)]. Socioeconomic advantage might protect against the progression to the early stages of neurocognitive disorders (CIND) and facilitate the potential reversion from mild cognitive impairment to a healthy cognitive state in later life. Lower levels of education affect the risk of mortality after the onset of dementia., (© 2024. The Author(s).)

Older adults are at risk of committing cognitive and decision-making errors due to the decline in cognitive functions. However, the understanding of the determining factors of cognitive errors among ageing adults is limited. In this study, we explored the role of various psychiatric factors, life satisfaction, and other socioeconomic, health and behavioural risk factors of committing cognitive errors among middle-aged and older adults in India. The study utilized the data from the experimental module of the Longitudinal Ageing Study in India (LASI) Wave-1 (2017-2018) with a sample of 12,754 adults aged 45 years and above. The cognitive error was measured using logical fallacies committed in the activity-based experiments. The study employed descriptive, bivariate statistics and multivariable logistic regression models to identify the factors associated with cognitive errors among the study participants. Depression (aOR = 1.28, 99%, CI: 1.16-1.41), life satisfaction (aOR = 0.99, 99%, CI: 0.98-1.00), and cognitive impairment (aOR = 1.13, 90% CI: 1.00-1.30) self-reported psychiatric) were significantly associated with higher odds of committing cognitive errors among the middle-aged and older adults. Also, ageing adults with low educational levels, functional limitations, sleep disturbances, smoking history, living in rural areas and belonging to scheduled tribes had a higher probability of committing cognitive errors. However, involvement in physical activity, reading habits and social interactions reduced the odds of cognitive errors among this sample. Mental health and well-being indicators, including depression, life satisfaction, cognitive impairment, and other health and behavioural health factors, determine cognitive errors among ageing adults. Programs and policies should be initiated to address these factors, reduce cognitive errors, and ensure active ageing., (© 2024. The Author(s).)

The main aim of this study was to explore the correlation between the platelet/high-density lipoprotein cholesterol ratio (PHR) and cognitive function in elderly individuals from the United States. This investigation leveraged data encompassing 2299 participants, all aged 60 years and above, from the National Health and Nutrition Examination Survey conducted from 2011 to 2014. Inclusion criteria were based on the availability of complete datasets for PHR and cognitive function assessments. The analytical approach incorporated multivariate logistic regression to discern the association between PHR and cognitive function. Additionally, the study employed restricted cubic splines (RCS) to explore potential non-linear relationships and subgroup analyses to identify variations in the observed associations across different demographic and clinical subgroups. In the fully adjusted model, an increment of 10 units in PHR was associated with a decline of 0.014 in cognitive scores (β=-0.014, 95% CI: -0.025, -0.002; P < 0.05). Compared to the lowest quartile, participants in the highest quartile exhibited a 38.4% increased prevalence of cognitive impairment per one-unit increase in PHR (OR = 1.384, 95% CI: 1.012, 1.893; P < 0.05). Subgroup analysis revealed consistent results regarding the relationship between PHR and cognitive impairment across all subgroups. A non-linear relationship between PHR and cognitive impairment was observed using RCS, indicating that an increase in PHR above 111.49 significantly elevated the incidence of cognitive impairment (P < 0.05). Our study demonstrates that a higher PHR is associated with a greater risk of cognitive decline in an older U.S. population, and although further validation is needed, this warrants consideration in clinical assessments and interventions., (© 2024. The Author(s).)

Arthritis often results in unmet healthcare needs for older adults with cognitive decline, who may struggle to communicate pain or recall symptoms. However, the risk factors for arthritis in this group remain underexplored. We addressed this gap by identifying and comparing arthritis risk factors among older adults with varying cognitive statuses. Data from 334 participants with cognitive decline and 808 participants with normal cognition were analysed using the Korean Longitudinal Study of Aging, tracking arthritis diagnoses over 12 years with Kaplan-Meier curves and Cox proportional hazards regression. Results showed 47.6% of older adults with cognitive decline developed arthritis, compared with 30.1% with normal cognition. Key risk factors for the cognitive decline group included depressive symptoms (hazard ratio [HR]: 1.87), living alone (HR: 1.66), infrequent social interactions (HR: 1.42), and greater dependency in daily activities (HR: 1.41). In the normal cognition group, additional chronic illnesses (HR: 1.41) and higher body mass index (HR: 1.09) were significant risk factors. Understanding these distinct risk factors is crucial for preventing and managing arthritis among at risk groups. Moreover, these findings can assist in developing comprehensive public health strategies integrating mental health and social support to improve health outcomes for older adults with cognitive decline., (© 2024. The Author(s).)

There has been an increasing focus on the interplay between physical frailty and cognitive impairment, as both conditions pose significant risks for life-threatening health complications and are receiving considerable attention in global geriatric health initiatives. A recent consensus introduces "cognitive frailty," denoting the co-existence of physical frailty and cognitive impairment without dementia. This study aims to ascertain the prevalence of cognitive frailty and investigate the factors contributing to gender differentials of cognitive frailty among older adults in India. This study has used the data from the nationally representative survey Longitudinal Ageing Study in India 2017-18. This study included a sample of 13,946 males and 14,989 females aged 60 and above. Descriptive and bivariate analyses were conducted. A proportion test was employed to assess gender disparities and determine the statistical significance of risk factors. Furthermore, multivariate decomposition analysis was performed to identify the extent to which various covariates contribute to explaining the gender differences observed in cognitive frailty. The overall prevalence of cognitive frailty was 4.4%. There was a significant gender difference in cognitive frailty among older adults in India (Difference: 4.3%; p-value < 0.001] with 2.1% (95% CI: 1.8-2.3) older males and 6.4% (95% CI: 6.0-6.8) older females suffering from cognitive frailty. The considerable gender gap in cognitive frailty would be reduced if women had similar levels of education (37% reduction) than men. Results highlight that increasing age, being a woman (AOR: 1.61; 95% CI: 1.33-1.95), out-of-wedlock, less education and non-working status (AOR:2.19; 95% CI: 1.71-2.80) were significantly associated with cognitive frailty. Poor nutritional status, and depression are also prone among the cognitively frail participants. Gender sensitive interventions improving education access for women are crucial. Developing countries like India urgently require a multidimensional approach to ensure appropriate and comprehensive healthcare for the elderly population., (© 2024. The Author(s).)

Loneliness and associated physical and cognitive health decline among the aging population is an important medical concern, exacerbated in times of abnormal isolation like the 2020-2021 Covid-19 pandemic lockdown. In this backdrop, recent "social prescribing" based health policy initiatives such as community groups as a support structure for the aging population assumes great importance. In this paper, we evaluate and quantify the impact of such social prescribing policies in combatting loneliness and related health degeneration of the aging population in times of abnormal isolation. To this end, we conduct a natural experiment across a sample of 618 individuals aged 65 and over with varying access to community groups during the Covid-19 lockdown period. Using a random-effects, probit model to compare the differences in health outcomes of participants with access to community groups (target) with those without access (control), we find that the target group was 2.65 times less likely to suffer from loneliness as compared to the control group, along with lower incidences of reported cardiovascular and cognitive health decline. These initial findings provide preliminary support in favor of the interventional power of social prescription tools in mitigating loneliness and its consequent negative health impact on the aging population., (© 2024. The Author(s).)

Previous studies have yielded inconsistent results regarding the association between chronic kidney disease (CKD) and the risk of cognitive impairment (CI). This study aimed to investigate the longitudinal association of CKD with CI risk in the Chinese middle-aged and older population. A total of 16,515 CI-free participants 45 years of age or older including 15,595 without CKD and 920 with CKD were followed from 2011 until 2018 (median [interquartile range]: 7 [5.5-7]) to detect incident CI. Over the follow-up, 648 participants developed CI. Data were analyzed using multi-adjusted Cox proportional hazard regression and Laplace regression. The incidence rate (IR) of CI was significantly higher in individuals with CKD at 11.46 per 1,000 person-years (95% confidence interval [CI], 8.90 to 14.76) than in those without CKD at 6.38 per 1,000 person-years (95% CI, 5.89 to 6.92). Compared to those without CKD, the hazard ratios of those with CKD was 1.56 (95% CI, 1.19 to 2.04) for CI. Participants with CKD in the middle-aged group (45-54 years) exhibited a heightened risk of CI in age-stratified analyses. CKD accelerated the onset of CI by 1.24 years (10th percentile difference [PD]; 95% CI, -2.03 to -0.43, p < 0.01). The findings from this study revealed a significantly increased risk of CI in individuals with CKD, especially in middle-aged population, where the risk appeared to be more pronounced. This observation underscores the importance of early detection and intervention strategies to alleviate the potential cognitive decline associated with CKD., (© 2024. The Author(s).)

Although it is generally recognized that sleep quality, depressive symptoms, and cognitive functions are related respectively, the main ambiguity comes from difficulties in determining their cause-effect relationships. The present study aimed to explore the longitudinal causation relationships among sleep quality, depressive symptoms, and cognitive functions in older people with mild cognitive impairment (MCI). A total of 134 patients from 24 communities in Ningbo City, Zhejiang Province, China with MCI were interviewed at baseline, while 124 of them were re-interviewed 2 months later, and 122 were re-interviewed 4 months later. The Patient Health Questionnaire-9, the Pittsburgh Sleep Quality Index and the Montreal Cognitive Assessment Scale were assessed in the interview. Cross-lagged models were tested to disentangle the relationships among sleep quality, depressive symptoms, and cognitive functions using structural equation modeling with latent variables on the four-mouth longitudinal data. The correlation coefficients between sleep quality and depressive symptoms were significant showing the stability across time points of assessment, while the correlation coefficient of cognitive function was not significant (r = 0.159, p > 0.05). The results of index of model fit indicated that the cross-lagged model was acceptable (CFI = 0.934, TLI = 0.899, RMSEA = 0.075, χ 2 /df = 1.684). The results of cross-lagged model analysis supported the complete mediating role of depressive symptoms in the association between sleep quality and cognitive functions, where worse sleep quality may lead to more severe depressive symptoms, which in turn leads to more severe cognitive decline. In Conclusion, sleep quality is significantly correlated with cognitive functions in patients with mild cognitive impairment, which association is fully mediated by depressive symptoms. Approaches addressing sleep quality and depressive symptoms are recommended and hold promise for the management of mild cognitive impairment., (© 2024. The Author(s).)

Alzheimer's disease (AD), the most prevalent form of dementia, requires early prediction for timely intervention. Current deep learning approaches, particularly those using traditional neural networks, face challenges such as handling high-dimensional data, interpreting complex relationships, and managing data bias. To address these limitations, we propose a framework utilizing graph neural networks (GNNs), which excel in modeling relationships within graph-structured data. Our study employs GNNs on data from the Alzheimer's Disease Neuroimaging Initiative for binary and multi-class classification across the three stages of AD: cognitively normal (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD). By incorporating comorbidity data derived from electronic health records, we achieved the most effective multi-classification results. Notably, the GNN model (Chebyshev Convolutional Neural Networks) demonstrated superior performance with a 0.98 accuracy in multi-class classification and 0.99, 0.93, and 0.94 in the AD/CN, AD/MCI, and CN/MCI binary tasks, respectively. The model's robustness was further validated using the Australian Imaging, Biomarker & Lifestyle dataset as an external validation set. This work contributes to the field by offering a robust, accurate, and cost-effective method for early AD prediction (CN vs. MCI), addressing key challenges in existing deep learning approaches., (© 2024. The Author(s).)

Cognitive impairment can potentially become a significant health concern in older adults. However, early effective diagnostic methods are still lacking. Therefore, we utilized the NHANES database in the US to investigate the relationship between serum uric acid to serum creatinine (SUA/SCR) ratio and cognitive impairment. In our study, a total of 3874 participants were included (2001-2002, 2011-2014). Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the SUA/SCR and cognitive impairment. In this study, the SUA/SCR was significantly lower in individuals with cognitive impairment. The logistic regression model, after adjusting for all covariates, revealed that the Q2-Q4 were 0.65 (95% CI 0.49, 0.86), 0.60 (95% CI 0.40, 0.90), 0.55 (95% CI 0.39, 0.77) respectively. This indicates that participants in the Q4 had a 45% reduced risk of cognitive impairment. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between SUA/SCR and cognitive impairment, with a turning point at 4.13. Subgroup analysis showed no statistically significant differences in the relationship between SUA/SCR and cognitive impairment among different subgroups (P > 0.05). Our findings indicate a negative correlation between the SUA/SCR and the risk of cognitive impairment in the population of adults aged 60 and above in the US. This suggests that the SUA/SCR holds promise as a potential indicator for cognitive impairment., (© 2024. The Author(s).)

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The cognitive problems are prominent in the context of global aging, and the traditional Mendelian randomization method is not applicable to ordered multi-categorical exposures. Therefore, we aimed to address this issue through the development of a method and to investigate the causal inference of cognitive-related lifestyle factors. The study sample was derived from the Chinese Longitudinal Healthy Longevity Survey, which included 897 older adults aged 65 + . This study used genome-wide association analysis to screen genetic loci as instrumental variables and innovatively combined maximum likelihood estimation to infer causal associations between ordered multi-categorical exposures (diet, exercise, etc.) and continuous outcomes (cognitive level). The causal inference method for ordered multi-categorical exposures developed in this study was simple, easy to implement, and able to effectively and reliably discover the potential causal associations between variables. Through this method, we found a potential positive causal association between exercise status and cognitive level in Chinese older adults ( β ^ = 1.883, 95%CI 0.182-3.512), in which there was no horizontal pleiotropy (p = 0.370). The study provided a causal inference method applicable to ordered multi-categorical exposures, that addressed the limitations of the traditional Mendelian randomization method., (© 2024. The Author(s).)

Vitamin D (VitD) is a naturally occurring, fat-soluble vitamin which regulates calcium and phosphate homeostasis in the human body and is also known to have a neuroprotective role. VitD deficiency has often been associated with impaired cognition and a higher risk of dementia. In this study, we aimed to explore the relationship between levels of VitD and cognitive functioning in adult individuals. 982 cognitively healthy adults (≥ 45 years) were recruited as part of the CBR-Tata Longitudinal Study for Aging (TLSA). Addenbrooke's cognitive examination-III (ACE-III) and Hindi mental status examination (HMSE) were used to measure cognitive functioning. 25-hydroxyvitamin D [25(OH)D] levels were measured from the collected serum sample and classified into three groups- deficient (< 20 ng/ml), insufficient (20-29 ng/ml) and normal (≥ 30 ng/ml). Statistical analysis was done using IBM SPSS software, version 28.0.1.1(15). The mean age of the participants was 61.24 ± 9 years. Among 982 participants, 572 (58%) were deficient, 224 (23%) insufficient and only 186 (19%) had normal levels of VitD. Kruskal-Wallis H test revealed a significant difference in age (p = 0.015) and education (p = 0.021) across VitD levels and the Chi-square test revealed a significant association between gender (p = 0.001) and dyslipidemia status (p = 0.045) with VitD levels. After adjusting for age, education, gender and dyslipidemia status, GLM revealed that individuals with deficient (p = 0.038) levels of VitD had lower scores in ACE-III verbal fluency as compared to normal. Additionally, we also found that 91.2% individuals who had VitD deficiency were also having dyslipidemia. It is concerning that VitD deficiency impacts lipid metabolism. Lower levels of VitD also negatively impacts verbal fluency in adult individuals. Verbal fluency involves higher order cognitive functions and this result provides us with a scope to further investigate the different domains of cognition in relation to VitD deficiency and other associated disorders., (© 2024. The Author(s).)

An inverse association between cancer and Alzheimer's disease (AD) has been demonstrated; however, the association between cancer and mild cognitive impairment (MCI), and the association between cancer and cognitive decline are yet to be clarified. The AIBL dataset was used to address these knowledge gaps. The crude and adjusted odds ratios for MCI/AD and cognitive decline were compared between participants with/without cancer (referred to as C+ and C- participants). A 37% reduction in odds for AD was observed in C+ participants compared to C- participants after adjusting for all confounders. The overall risk for MCI and AD in C+ participants was reduced by 27% and 31%, respectively. The odds of cognitive decline from MCI to AD was reduced by 59% in C+ participants after adjusting for all confounders. The risk of cognitive decline from MCI to AD was halved in C+ participants. The estimated mean change in Clinical Dementia Rating-Sum of boxes (CDR-SOB) score per year was 0.23 units/year higher in C- participants than in C+ participants. Overall, an inverse association between cancer and MCI/AD was observed in AIBL, which is in line with previous reports. Importantly, an inverse association between cancer and cognitive decline has also been identified., (© 2024. The Author(s).)

This study aims to assess the prevalence of geriatric syndromes and identify factors associated with multiple geriatric syndromes in community-dwelling older adults in China. We utilized a convenience sampling method to recruit older adults and from one rural and one urban community in Chengdu, China, from October 2022 to March 2023. A total of 706 older adults aged 60 years or older were included. Ten geriatric syndromes were investigated including two mental disorders: depressive symptoms, cognitive impairment; and eight somatic disorders: pain, falls, sleep disturbance, constipation, polypharmacy, multimorbidity, malnutrition and frailty. Multiple geriatric syndromes were defined as an individual having two or more geriatric syndromes. The data obtained were analysed using descriptive statistics. The independent risk factors for multiple geriatric syndromes were assessed using a logistic regression model. This study found that 90.5% of the participants had at least one geriatric syndrome, with 72.8% experiencing multiple geriatric syndromes. The top four geriatric syndromes in our study were polypharmacy (58.5%), malnutrition/at risk of malnutrition (43.1%), multimorbidity (42.1%), and frailty/prefrailty (34.3%). Of the older adults, 368(52.1%) had only somatic disorders, 18(2.5%) had only mental disorders and 253 (35.8%) had somatic-mental disorders. According to the logistic regression analysis, residence, age, marriage, BMI, and self-related health were significantly associated with multiple geriatric syndromes among older adults. This study highlights that multiple geriatric syndromes are prevalent among community-dwelling older adults in China, and underscores the significance of certain demographic factors in their occurrence. Future longitudinal studies are needed to establish the temporal relationship between multiple geriatric syndromes and these demographic factors, as well as to explore causal relationships and effective prevention strategies for geriatric syndrome., (© 2024. The Author(s).)

As life expectancy increases and the population grows, the number of surgeries performed each year is likely to continue to increase. We evaluated whether surgery with general anesthesia increases risk for cognitive impairment in a Chinese elderly community population. The current data was obtained from the China Longitudinal Aging Study (cohort 1) and Shanghai Brain Aging study (cohort 2). Cohort 1 included 1545 elderly people with normal cognitive function, who underwent a screening process that included physical examination, medical history, baseline and 1-year follow-up assessments of cognitive function by a face-to-face interview. Cohort 2 included an additional 194 elderly people with normal cognitive function, all of whom, unlike cohort 1, underwent T1-phase MR imaging scans. In cohort 1, 127 elderly people with normal cognitive function transformed into mild cognitive impairment, 27 into dementia, while 1391 still maintained normal cognitive function. By using Cox regression analysis, we found that surgery with general anesthesia was a risk factor for cognitive impairment (p = 0.013, HR = 1.506, 95% CI 1.091-2.078); In cohort 2, we found that elderly people with a history of surgery with general anesthesia had lower Montreal Cognitive Assessment (MoCA) scores and smaller right amygdala volume (p < 0.05). Through correlation analysis, we found that the volume of the right amygdala was significantly correlated (p = 0.003, r = 0.212) with MoCA. Then by using the linear regression analysis (mediation model), we found that surgery with general anesthesia directly affected the MoCA score by affecting the volume of the right amygdala (B = 1.315, p = 0.036 95% CI 0.088-2.542). We confirm surgery with general anesthesia as a risk factor for cognitive impairment, and its mechanism may be related to its effect on the volume of the right amygdala., (© 2023. Springer Nature Limited.)

Long-term persistent symptoms of COVID-19 affect 30-80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities. The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286). Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model. The results showed an overall medium-high effect size (g = -.68, p = .02) with a 95% CI (-1.05 to -.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p < .001; I 2  = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls. Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear., (© 2023. The Author(s).)

The objective of this study was to investigate the potential association between the use of four frequently prescribed drug classes, namely antihypertensive drugs, statins, selective serotonin reuptake inhibitors, and proton-pump inhibitors, and the likelihood of disease progression from mild cognitive impairment (MCI) to dementia using electronic health records (EHRs). We conducted a retrospective cohort study using observational EHRs from a cohort of approximately 2 million patients seen at a large, multi-specialty urban academic medical center in New York City, USA between 2008 and 2020 to automatically emulate the randomized controlled trials. For each drug class, two exposure groups were identified based on the prescription orders documented in the EHRs following their MCI diagnosis. During follow-up, we measured drug efficacy based on the incidence of dementia and estimated the average treatment effect (ATE) of various drugs. To ensure the robustness of our findings, we confirmed the ATE estimates via bootstrapping and presented associated 95% confidence intervals (CIs). Our analysis identified 14,269 MCI patients, among whom 2501 (17.5%) progressed to dementia. Using average treatment estimation and bootstrapping confirmation, we observed that drugs including rosuvastatin (ATE = - 0.0140 [- 0.0191, - 0.0088], p value < 0.001), citalopram (ATE = - 0.1128 [- 0.125, - 0.1005], p value < 0.001), escitalopram (ATE = - 0.0560 [- 0.0615, - 0.0506], p value < 0.001), and omeprazole (ATE = - 0.0201 [- 0.0299, - 0.0103], p value < 0.001) have a statistically significant association in slowing the progression from MCI to dementia. The findings from this study support the commonly prescribed drugs in altering the progression from MCI to dementia and warrant further investigation., (© 2023. The Author(s).)

Whether cumulative smoking exposure is associated with cognitive decline among older adults remains unresolved. To address this question, we used data from the Neurological Disorders in Central Spain (NEDICES) cohort study, in which 2624 older adults were evaluated at two-time points separated by three years. A 37-item version of the Mini-Mental State Examination (MMSE-37) was administered at two visits to assess cognitive change. Regarding smoking exposure, we calculated an individual baseline score based on pack-years (i.e., packs of cigarettes smoked per day multiplied by years of smoking) in current and former smokers. Thus, smoking exposure was categorized into tertiles (low: < 19.0, medium: 19.0-47.0, and high: > 47.0). We used multivariable generalized estimating equation models to assess associations between pack-years and smoking status with 37-MMSE total score change from baseline to follow-up. The MMSE-37 total score had a decline of 1.05 points (confidence interval [CI] 95% 0.62 to 1.48) in the lower tertile of pack-years, 1.16 (CI 95% 0.70 to 1.62) in the middle tertile and 1.17 (CI 95% 0.70 to 1.65) in the higher tertile compared to never smokers, after adjusting for several demographic and clinical variables. The same occurred with smoking status, i.e., a decline of 1.33 (CI 95% 0.87 to 1.79) in current smokers and 1.01 (CI 95% 0.63 to 1.40) in former smokers. Our study provides evidence of the cumulative effect of smoking on cognition in older adults. Using a prospective population-based design, we demonstrated that cumulative smoking exposure was associated with cognitive decline in non-demented older adults. More population-based evidence is required to elucidate this association in older adults without dementia., (© 2023. The Author(s).)

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) population and African Americans from the Atherosclerosis Risk In Communities (ARIC) study. We identified 5 Amerindian and 14 African enriched variants with an expected moderate effect. A suggestive significant interaction (p-value = 0.01) was found for one African-enriched variant, rs8112679, located in the ZNF222 gene fourth exon. Our results suggest there are no ancestry-enriched variants with large effect sizes of interaction effects with APOE-ɛ4 on MCI in the APOE region in the Hispanic/Latino population. Further studies are needed in larger datasets to identify potential interactions with smaller effect sizes., (© 2023. The Author(s).)

This research explored experiences across three cognitive function groups (no impairment, mild impairment, and dementia) with respect to shielding (either self-isolating or staying at home), COVID-19 infection, and access to health/care services during the COVID-19 pandemic. Analyses were conducted using data from the English Longitudinal Study of Ageing (ELSA) COVID-19 sub-study collected in 2020. We report bivariate estimates across our outcomes of interest by cognitive function group along with multivariate regression results adjusting for demographic, socioeconomic, geographic, and health characteristics. Rates of shielding were high across all cognitive function groups and three measured time points (April, June/July, and Nov/Dec 2020), ranging from 74.6% (95% confidence interval 72.9-76.2) for no impairment in Nov/Dec to 96.7% (92.0-98.7) for dementia in April (bivariate analysis). 44.1% (33.5-55.3) of those with dementia experienced disruption in access to community health services by June/July compared to 34.9% (33.2-36.7) for no impairment. A higher proportion of those with mild impairment reported hospital-based cancellations in June/July (23.1% (20.1-26.4)) and Nov/Dec (16.3% (13.4-19.7)) than those with no impairment (18.0% (16.6-19.4) and 11.7% (10.6-12.9)). Multivariate adjusted models found that those with dementia were 2.4 (1.1-5.0) times more likely than those with no impairment to be shielding in June/July. All other multivariate analyses found no statistically significant differences between cognitive function groups. People with dementia were more likely than people with no impairment to be shielding early in the pandemic, but importantly they were no more likely to experience disruption to services or hospital treatment., (© 2023. The Author(s).)

Criminal behaviour has previously been associated with an increased risk for several mental health problems, but little is known about the association between criminal behaviour and dementia. We aimed to examine how the criminal background (type of crime, number of convictions, length of the sentence) is associated with dementia and mild cognitive impairment (MCI), and how mental and physical health disorders and educational attainment influenced these associations. A nationwide cohort of 3,617,028 individuals born between 1932 and 1962 were linked with criminal and medical records using Swedish national registers. We used Cox regression models to examine the associations. Increased risks for dementia (Hazard ratios (HRs) 1.54, 95% confidence interval (CI) 1.50-1.57) and MCI (1.55, 1.50-1.61) were found in individuals with criminal background, particularly among those who committed violent or several crimes, or with long sentences. After full adjustment of covariates, the associations attenuated but remained statistically significant for dementia (1.25, 1.22-1.28) and MCI (1.27, 1.22-1.32). The attenuation was mostly explained by mental health problems -depression, anxiety, schizophrenia spectrum disorders, substance use disorder (SUD), and bipolar disorder- (dementia: 1.34, 1.31-1.37; MCI: 1.35, 1.30-1.40). SUD contributed the most to attenuate the associations. Our results may provide important insights to health and penal systems by showing the importance of considering the severity of the criminal background and life-course mental health when assessing the risk of neurodegenerative disorders., (© 2023. The Author(s).)

Cognition capacity is essentially age-dependent and it is associated with the overall well-being of an individual. The public health aspects of cognitive research primarily focus on the possible delaying of cognitive decline among the older adult population. In this context, using the most recent round of the Longitudinal Ageing Study in India, 2017-2018 data, this study examines the cognition capacity among older adults aged 45 and above subject to their nutritional health and health behaviour (tobacco and alcohol consumption). It is observed that almost one in every tenth individual (10%) above 45 years of age in India shows low cognition scores. Low cognition is much more prevalent among 60 + females than males. Around one-fifth of the underweight older adults (18%) demonstrate low cognition capacity among them. Of those older adults who consume only tobacco, 11% of them demonstrate low cognition than the rest. The partial proportional odds model estimation shows that older adults are at higher risk of developing low cognition with increasing age and beyond age 65, the individuals carry a critically higher risk to experience low cognition. The estimation also shows that with increasing age older adults are higher likely to experience poor cognition independent of nutritional status, but underweight older adults are comparatively more likely to experience low cognition followed by normal and overweight older adults. In terms of alcohol-tobacco consumption behaviour, older adults who consume both are more likely to experience low cognition with increasing age followed by 'only alcohol consumers', and 'only tobacco consumers'., (© 2022. The Author(s).)

Recent studies suggest that sensory impairment is related to cognitive function at older ages. Therefore, we aimed to investigate the impact of sensory impairment on cognitive function in the Korean population. We used the Korean Longitudinal Study of Aging data from 2006 to 2018. Cognitive function was measured by the Korean version of the Mini-Mental State Examination scale. A score < 24 at the time of assessment was defined as cognitive impairment. Sensory impairment was assessed according to the self-reported levels of hearing or vision, and the development of sensory impairment was investigated using records of prior survey. We used the generalized estimating equation model to determine association between cognitive function and sensory impairment. A total of 4844 participants (age range: 47-95 years; mean age: 58) were included in the study. Compared to people without sensory impairment, people with a single sensory impairment of hearing or vision had a higher risk of cognitive impairment (odds ratio (OR) = 1.65 [95% confidence interval (CI), 1.49-1.82]). People with dual sensory impairment had the greatest risk of cognitive impairment (OR = 3.23 [95% CI, 2.52-4.12]). The findings suggested the need for timely assessment of sensory function in older persons, which may be useful in identifying individuals at risk for cognitive impairment., (© 2022. The Author(s).)

There is a small body of evidence suggesting that unclean cooking fuel use may be associated with cognitive decline. However, to date, no study has investigated the association between unclean cooking fuel and mild cognitive impairment (MCI). Thus, we investigated the association between cooking fuel type or ventilation type and MCI among adults aged ≥ 65 years using nationally representative datasets from six low- and middle-income countries. Cross-sectional, community-based data from the World Health Organization (WHO) Study on global Ageing and adult health (SAGE) were analyzed. MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Unclean cooking fuel referred to kerosene/paraffin, coal/charcoal, wood, agriculture/crop, animal dung, and shrubs/grass. Multivariable logistic regression analysis was conducted to assess associations. Data on 13,623 individuals were analyzed [mean (SD) age 72.8 (11.0) years; 45.5% males]. Unclean cooking fuel (vs. clean cooking fuel) was associated with a significant 1.48 (95% CI = 1.08-2.03) times higher odds for MCI. Having no chimney or hood for cooking ventilation was also associated with significantly higher odds for MCI (OR = 1.88; 95% CI = 1.25-2.84). Unclean cooking fuel use and lack of chimney or hood for cooking ventilation were associated with higher odds for MCI. Findings support the implementation of the United Nations Sustainable Goal 7, which advocates affordable, reliable, sustainable, and modern energy for all, as this may also help reduce MCI and ultimately dementia., (© 2022. The Author(s).)

Substantial evidence indicates a huge potential for risk reduction of cognitive decline and dementia based on modifiable health and lifestyle factors. To maximize the chances for risk reduction, it is useful to investigate associations of social determinants and lifestyle for brain health. We computed the "LIfestyle for BRAin health" (LIBRA) score for baseline participants of the Leipzig Research Centre for Civilization Diseases (LIFE) Adult Study, a population-based urban cohort in Germany. LIBRA predicts dementia in midlife and early late life populations, comprising 12 modifiable risk factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive inactivity). Associations of social determinants (living situation, marital status, social isolation, education, net equivalence income, occupational status, socioeconomic status/SES, employment) with LIBRA were inspected using age- and sex-adjusted multivariable linear regression analysis. Z-standardization and sampling weights were applied. Participants (n = 6203) were M = 57.4 (SD = 10.6, range 40-79) years old and without dementia, 53.0% were women. Except for marital status, all considered social determinants were significantly associated with LIBRA. Beta coefficients for the association with higher LIBRA scores were most pronounced for low SES (β = 0.80, 95% CI [0.72-0.88]; p < 0.001) and middle SES (β = 0.55, 95% CI [0.47-0.62]; p < 0.001). Social determinants, particularly socioeconomic factors, are associated with lifestyle for brain health, and should thus be addressed in risk reduction strategies for cognitive decline and dementia. A social-ecological public health perspective on risk reduction might be more effective and equitable than focusing on individual lifestyle behaviors alone., (© 2022. The Author(s).)

Large population-based studies on the associations of childhood factors with late-life cognition are lacking in many low and middle income countries including India. In this study, we assessed the prevalence of late-life cognitive impairment and examined the associations of childhood socioeconomic status (SES) and health conditions with cognitive impairment among older adults in India. Data for this study were derived from the Longitudinal Ageing Study in India conducted in 2017-18. The effective sample size was 31,464 older adults aged 60 years and above. Cognitive functioning was measured through five global domains (memory, orientation, arithmetic function, executive function, and object naming). The overall score ranged between 0 and 43, and the score was reversed indicating cognitive impairment. Descriptive statistics along with mean scores of cognitive impairment were presented. Additionally, moderated multivariable linear regression models were employed to examine the association between explanatory variables, including childhood SES and health conditions and late-life cognitive impairment. The mean score of cognitive functioning among the study participants was 21.72 (CI 2.64-21.80). About 15% of older adults had poor health conditions, and 44% had lower financial status during their childhood. Older adults who had a fair health during their childhood were more likely to suffer from cognitive impairment in comparison to older adults who had good health during their childhood (Coef: 0.60; CI 0.39, 0.81). In comparison to older adults who had good childhood financial status, those who had poor childhood financial status were more likely to suffer from cognitive impairment (Coef: 0.81; CI 0.56, 1.07). Older adults who had fair childhood health status and poor childhood financial status were more likely to suffer from cognitive impairment in comparison to older adults who had good childhood health and good financial status (Coef: 1.26; CI 0.86, 1.66). Social policies such as improving educational and financial resources in disadvantaged communities and socioeconomically poor children and their families, would help to enhance a better cognitive ageing and a healthy and dignified life in old age., (© 2022. The Author(s).)

This study aimed to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cognitive impairment and explore the effect modification by the inflammatory status. A total of 4400 community-based participants aged 50-64 years from the Cardiovascular and Metabolic Disease Etiology Research Center were included in this cross-sectional study. NAFLD was identified as the Fatty Liver Index 30 or higher in the absence of excessive alcohol consumption. Cognitive impairment was defined as the total score of the Mini-Mental State Examination (cutoff 24). The inflammatory status was evaluated using white blood cell (WBC) and high-sensitivity C-reactive protein (hsCRP). Multivariate logistic regression analyses were performed. Stratified analyses by the WBC count (the highest quartile) and the hsCRP level (≥ 1.0 mg/dL vs. < 1.0 mg/dL) were conducted. Participants with NAFLD showed an increased prevalence of cognitive impairment (odds ratio [OR] = 1.26; 95% confidence interval [CI] = 1.04-1.52) compared with the non-NAFLD population. In women, this association was significantly stronger in the highest quartile WBC group than in lower WBC group (OR = 1.81; 95% CI = 1.19-2.74 vs. OR = 1.02; 95% CI = 0.78-1.33, p-interaction = 0.05). NAFLD was positively associated with a higher proportion of cognitive impairment, and this association was stronger in women with higher inflammatory status., (© 2022. The Author(s).)

Due to different nature of social engagements of older adults in South Asian countries specially attributed to the traditional family-based care and support, beneficial effects of religiosity and religious involvement on mental health and cognitive function in older age might be different than those in the Western world. Yet, there is a paucity of research in these countries on the role of religion in moderating the relationship between late life depression and cognition. This study explored the association of depressive symptoms with cognitive impairment and the moderating effects of religiosity and religious participation in those associations among older Indian adults. A cross-sectional study was conducted on data that were drawn from the Longitudinal Ageing Study in India wave-1, collected during 2017-2018. The sample size comprised of 31,464 older adults aged 60 years and above. Shortened 10-item Centre for Epidemiologic Studies Depression Scale was used to measure depressive symptoms. Items from the Mini-Mental State Examination and the cognitive module of the China Health and Retirement Longitudinal Study and the Mexican Health and Aging Study were adapted for measuring cognitive impairment. Moderated multiple linear regression models were used to test the research hypotheses of the study. The proportion of older adults who reported religion as less important to them was 21.24%, whereas, only 19.31% of the respondents participated in religious activities. The mean score of cognitive impairment (on a scale of 0-43) in the current sample was 19.43 [confidence interval (CI): 19.32-19.53] among men and 23.55 [CI: 23.44-23.66] among women. Older adults with depressive symptoms had significantly higher likelihood of cognitive impairment [aCoef: 0.18, CI: 0.16-0.20] in comparison to older adults with no depressive symptoms. Older individuals who were religious were significantly less likely to have cognitive impairment [aCoef: - 0.43, CI: - 0.61 to - 0.25] than their non-religious counterparts. Compared to older adults who did not participate in religious activities, those who participated in religious activities were less likely [aCoef: - 0.52, CI: - 0.69 to - 0.34] to have cognitive impairment. Further, significant moderating effects of religiosity and religious participation in the relationship between depressive symptoms and cognitive impairment were observed. The current study contributes to advancing knowledge about the mental health benefits of religiosity and religious participation by focusing on older adults in India who culturally have limited chances to participate in social activities. The findings suggest that older adults with depressive symptoms may participate in religious activities which may reduce their chances of cognitive impairment. This protective effect of religiosity and religious participation on late life cognitive health has important implications for promoting alternative social support mechanisms for older adults in terms of enhancing their mental wellbeing and contributing to active aging., (© 2022. The Author(s).)

Frail older adults are vulnerable to stressors; thus, sleep related cognition impairment might more greatly affect frail than healthy older adults. In the present study, we investigated whether the association between sleep problems and cognition varies with physical frailty status (modified from Fried et al.). Participants 55 years and older who completed a baseline and follow-up questionnaire (median follow-up: 5.5 years), were included in the analysis. Sleep parameters were evaluated in an interview at the baseline. Cognitive decline was defined as a loss of 3 or more points on the Mini-Mental State Examination (MMSE) at follow-up. Associations between sleep problems and cognitive decline were examined using logistic regression and were stratified by baseline physical frailty status, adjusted for potential confounders. A short total sleep duration (< 5 vs. 7-9 h, odds ratio (OR) = 1.88, 95% confidence interval (CI) 1.18-3.00), excessive daytime sleepiness (OR = 1.49, 95% CI 1.04-2.13), low sleep efficiency (< 65% vs. ≥ 85%, OR = 1.62, 95% CI 1.07-2.46), and insomnia complaints (OR = 2.34, 95% CI 1.23-4.43) were associated with MMSE decline in physically robust. The association was stronger for the sleep summary score, which summarized abnormal sleep duration, excessive daytime sleepiness, and insomnia complaints ([Formula: see text] 2 vs. 0, OR = 3.79, 95% CI 2.10-6.85, p < 0.0001). Due to the low prevalence of frailty in this community-dwelling population, the statistical power to detect an association was low. More evidence is needed to clarify the role of sleep in the progression of cognitive decline in frail individuals., (© 2022. The Author(s).)

The factors associated with cognitive decline among older adults include physical activity and fruit and vegetable intake. However, the long-term effects of concomitant physical activity and fruit and vegetable intake are unknown. This 16-year longitudinal study explored the joint effect of mitigating cognitive decline in a cohort of older Taiwanese individuals. Five population-based surveys (Taiwan Longitudinal Survey on Aging [1999-2015]) involving 4440 respondents over 53 years old in 1999 were conducted. Cognitive function was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). The demographic, socioeconomic, health-related, behavioral, and disease status covariates were adjusted in the regression analysis. Trends in cognitive decline were observed over 16 years. The risk of cognitive decline decreased by 63% when high physical activity and high fruit and vegetable intake were combined (odds ratio 0.37; 95% confidence interval 0.23-0.59), indicating a potential combined effect of physical activity and fruit and vegetable intake on mitigating cognitive decline. These personal actions are safe, effective, and economical approaches to health promotion and disease prevention., (© 2022. The Author(s).)

The recent increase in the older adult population has led to a higher prevalence of cognitive impairment, which is often overlooked in routine health examinations. Citizens aged 50-89 years were targeted for this cohort survey by random sampling from the resident registry of a cooperating town in 2014. A total of 411 participants (202 male and 209 female) were enrolled. We analyzed the distribution of cognitive function test scores as determined by Montreal Cognitive Assessment and Mini-Mental State Examination tests in each age (50's, 60's, 70's and 80's) and sex group to examine whether cognitive decline could be detected by sagittal spinal balance measurement based on a radiological approach. Sagittal spinal balance was quantitatively measured as sagittal vertical axis (SVA). We observed significant associations for higher age and/or SVA anteriorization with lower cognitive function. In males, spinal balance anteriorization was associated with cognitive decline independently of age, with combinations of age and SVA also making valid cognitive decline determinations; male cases of SVA ≥ 100 mm at any age, SVA ≥ 90 mm at ≥ 70 years, and SVA ≥ 70 mm at ≥ 80 years were all more likely to have cognitive decline than cases below those values. For females, cognitive decline was more likely in cases of SVA ≥ 70 mm, regardless of age. Thus, spinal balance anteriorization can be regarded as an easily visible indicator of latent cognitive decline in community-dwelling older people., (© 2022. The Author(s).)

Cognitive frailty (CF) is a clinical condition defined by the presence of both mild cognitive impairment (MCI) and physical frailty (PF). Elderly with CF are at greater risk of dementia than those with MCI or PF alone, but there are few known clinical or neuroimaging features to reliably distinguish CF from PF or MCI. We therefore conducted a population-based cross-sectional study of community elderly combining physical, cognitive, neuropsychiatric, and multisequence magnetic resonance imaging (MRI) evaluations. The MRI evaluation parameters included white matter (WM) lesion volumes, perivascular and deep subcortical WM lesion grades, lacunar infarct prevalence, microbleed number, and regional medial temporal lobe (MTL) volumes. Participants were divided into 4 groups according to the presence or absence of MCI and PF-(1) no MCI, PF (n = 27); (2) no PF, MCI (n = 119); (3) CF (MCI + PF) (n = 21), (4) normal controls (n = 716). Unique features of CF included shorter one-leg standing time; severe depressive symptoms; and MRI signs of significantly more WM lesions, lacunar infarcts, small-vessel disease lesions, microbleeds, and reduced MTL volumes. These unique deficits suggest that interventions for CF prevention and treatment should focus on motor skills, depressive symptoms, and vascular disease risk factor control., (© 2022. The Author(s).)

Cognitive impairment and dementia are age-related major public health concerns in the elderly population. It is a major cause of disability, dependency, and poor quality of life. However, in Ethiopia, the magnitude of this cognitive impairment among the elderly community was not investigated. Hence, this study sought to determine the prevalence of cognitive impairment and associated factors among mature and older adults living in the community of Gondar town, Ethiopia, in 2020. A community-based cross-sectional study was conducted at Gondar town, from February 20 to April 30, 2020. Using a single-stage cluster sampling technique, 403 study participants were recruited. Data was collected by a pretested interviewer-administered structured questionnaire which consisting of sociodemographic variables, the Oslo Social Support Scale, and a Standardized Mini-mental State Examination (SMMSE) tool. Epi data version 3.0 was used to enter coded data and then exported into STATA 14 for analysis. Variables with a p-value < 0.25 in the bi-variable logistic regression were included in the multivariable regression. From multivariable logistic regression, variables having a p-value ≤ 0.05 were declared as statistically significant variables. In this study, a total of 403 study participants were involved, and 393 (97.5%) of them completed the survey. Among older participants screened for cognitive impairment, 43.8% was positive for cognitive impairment with a 95% CI (38.8-48.7%). The majority of the participants were (57.5%) male and (44.8%) aged over 60 years. After adjustment, the variables associated with cognitive impairment were age ≥ 75 years [odds ratio (OR) = 7.03, 95% CI 2.78-17.77] and between 61 and 74 years [OR = 3.18, 95% CI 1.81-5.59], and unable to read and write [OR = 5.05, 95% CI 2.04-12.50], low income level [OR = 2.60, 95% CI 1.26-5.20], being female [OR = 2.52, 95% CI 1.50-4.26], poor social support [OR = 2.50, 95% CI 1.30-4.81], and rural residence [OR = 2.39, 95% CI 1.26-4.51]. The prevalence of older participants who screened positively for cognitive impairment was high at Gondar town. The independent predictors of cognitive impairment among older individuals were older age, being unable to read and write, being female, low income, poor social support, and rural dwelling. Therefore, routine screening and social support, as well as free healthcare services for the mature and older community, are needed. Moreover, we strongly recommend the next researcher to use a diagnosis tool to estimate the actual prevalence of the problems among older people., (© 2022. The Author(s).)

The relationship between exposure to household air pollution (HAP) from solid fuel use and cognition remains poorly understood. Among 401 older adults in peri-urban northern China enrolled in the INTERMAP-China Prospective Study, we estimated the associations between exposure to HAP and z-standardized domain-specific and overall cognitive scores from the Montreal Cognitive Assessment. Interquartile range increases in exposures to fine particulate matter (53.2-µg/m 3 ) and black carbon (0.9-µg/m 3 ) were linearly associated with lower overall cognition [- 0.13 (95% confidence interval: - 0.22, - 0.04) and - 0.10 (- 0.19, - 0.01), respectively]. Using solid fuel indoors and greater intensity of its use were also associated with lower overall cognition (range of point estimates: - 0.13 to - 0.03), though confidence intervals included zero. Among individual cognitive domains, attention had the largest associations with most exposure measures. Our findings indicate that exposure to HAP may be a dose-dependent risk factor for cognitive impairment. As exposure to HAP remains pervasive in China and worldwide, reducing exposure through the promotion of less-polluting stoves and fuels may be a population-wide intervention strategy to lessen the burden of cognitive impairment., (© 2022. The Author(s).)

In a culturally different and low-resource setting, where lifestyle habits, including dietary pattern and physical activities differ from those in high-income countries, the association between physical activity and cognition is expected to differ. We aimed to investigate the association between physical activity and cognitive functioning after controlling for potential confounders among older adults in India. Furthermore, gender differences in this relationship were analyzed. Using a national-level data from the Longitudinal Ageing Study in India (2017-2018), this paper employed propensity score matching (PSM) approach to examine the association between physical activities and cognitive functioning among Indian older adults. Cognitive impairment was measured through five broad domains (memory, orientation, arithmetic function, executive function, and object naming). We limit our sample to older adults aged 60 + years, and our final dataset contains 31,464 participants (men = 16,366, and women = 15,098). The results indicated that older adults who engaged in frequent physical activity have greater cognitive functioning than older adults without physical activity after adjusting for various individual, health, lifestyle, and household factors. This association holds true for both older men and older women. The results from the PSM revealed that the cognitive function score was increased by 0.98 and 1.32 points for the frequently physically active older men and women population, respectively. The results demonstrate the possible beneficial effects of frequent physical activity on cognitive functioning among older adults. Thus, regular physical activity can be considered as an effective lifestyle factor to promote healthy cognitive aging., (© 2022. The Author(s).)

Autoantibodies are self-antigen reactive antibodies that play diverse roles in the normal immune system, tissue homeostasis, and autoimmune and neurodegenerative diseases. Anti-neuronal autoantibodies have been detected in neurodegenerative disease serum, with unclear significance. To identify diagnostic biomarkers of Alzheimer's disease (AD), we analyzed serum autoantibody profiles of the HuProt proteome microarray using the discovery set of cognitively normal control (NC, n = 5) and AD (n = 5) subjects. Approximately 1.5-fold higher numbers of autoantibodies were detected in the AD group (98.0 ± 39.9/person) than the NC group (66.0 ± 39.6/person). Of the autoantigen candidates detected in the HuProt microarray, five autoantigens were finally selected for the ELISA-based validation experiment using the validation set including age- and gender-matched normal (NC, n = 44), mild cognitive impairment (MCI, n = 44) and AD (n = 44) subjects. The serum levels of four autoantibodies including anti-ATCAY, HIST1H3F, NME7 and PAIP2 IgG were significantly different among NC, MCI and/or AD groups. Specifically, the anti-ATCAY autoantibody level was significantly higher in the AD (p = 0.003) and MCI (p = 0.015) groups compared to the NC group. The anti-ATCAY autoantibody level was also significantly correlated with neuropsychological scores of MMSE (r s  = - 0.229, p = 0.012), K-MoCA (r s  = - 0.270, p = 0.003), and CDR scores (r s  = 0.218, p = 0.016). In addition, a single or combined occurrence frequency of anti-ATCAY and anti-PAIP2 autoantibodies was significantly associated with the risk of MCI and AD. This study indicates that anti-ATCAY and anti-PAIP2 autoantibodies could be a potential diagnostic biomarker of AD., (© 2022. The Author(s).)

Therapeutic targets for halting the progression of Alzheimer's disease pathology are lacking. Recent evidence suggests that APOE4, but not APOE3, activates the Cyclophilin-A matrix metalloproteinase-9 (CypA-MMP9) pathway, leading to an accelerated breakdown of the blood-brain barrier (BBB) and thereby causing neuronal and synaptic dysfunction. Furthermore, blockade of the CypA-MMP9 pathway in APOE4 knock-in mice restores BBB integrity and subsequently normalizes neuronal and synaptic function. Thus, CypA has been suggested as a potential target for treating APOE4 mediated neurovascular injury and the resulting neuronal dysfunction and degeneration. The odds of drug targets passing through clinical trials are greatly increased if they are supported by genomic evidence. We found little evidence to suggest that CypA or MMP9 affects the risk of Alzheimer's disease or cognitive impairment using two-sample Mendelian randomization and polygenic risk score analysis in humans. This casts doubt on whether they are likely to represent effective drug targets for cognitive impairment in human APOE4 carriers., (© 2022. The Author(s).)

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer's dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer's disease., (© 2021. The Author(s).)

There has been increasing interest in finding non-invasive biomarkers for neurodegenerative diseases such as Alzheimer's disease (AD). This observational study investigated AD-specific biomarkers in tear fluid. Tear fluid was collected from a total of 65 subjects, including 23 patients with subjective cognitive decline (SCD), 22 patients with mild cognitive impairment (MCI), 11 dementia patients and 9 healthy controls (HC). Levels of amyloid-beta peptides (AB38, AB40, AB42), total-tau (t-tau) and phosphorylated-tau (p-tau) were determined using multiplex immunoassays. Levels of AB40 and t-tau were detectable in the vast majority (> 94%) of tear fluid samples. Cerebrospinal fluid (CSF) was available from a subset of patients. In this group, tear t-tau levels were significantly higher in people with dementia compared to SCD patients. Tear t-tau levels were elevated in patients with neurodegeneration (classified according to the A/T/N system) compared to patients without neurodegeneration. Negative correlations were found between CSF AB42 and CSF t-tau, and between CSF AB42 and tear t-tau. In summary, this study shows the potential of tau proteins in tear fluid to be associated with disease severity and neurodegeneration., (© 2021. The Author(s).)

The aim of the study was a systematic evaluation of cognitive development in individuals with glutaric aciduria type 1 (GA1), a rare neurometabolic disorder, identified by newborn screening in Germany. This national, prospective, observational, multi-centre study includes 107 individuals with confirmed GA1 identified by newborn screening between 1999 and 2020 in Germany. Clinical status, development, and IQ were assessed using standardized tests. Impact of interventional and non-interventional parameters on cognitive outcome was evaluated. The majority of tested individuals (n = 72) showed stable IQ values with age (n = 56 with IQ test; median test age 11 years) but a significantly lower performance (median [IQR] IQ 87 [78-98]) than in general population, particularly in individuals with a biochemical high excreter phenotype (84 [75-96]) compared to the low excreter group (98 [92-105]; p = 0.0164). For all patients, IQ results were homogenous on subscale levels. Sex, clinical motor phenotype and quality of metabolic treatment had no impact on cognitive functions. Long-term neurologic outcome in GA1 involves both motor and cognitive functions. The biochemical high excreter phenotype is the major risk factor for cognitive impairment while cognitive functions do not appear to be impacted by current therapy and striatal damage. These findings implicate the necessity of new treatment concepts., (© 2021. The Author(s).)

This study investigated the association between visual impairment and cognitive decline among the elderly in Taiwan. The data were obtained from a government-sponsored, annual physical examination program for elderly citizens ≥ 65 years in Taipei City during 2005-2012. Distance presenting visual acuity was measured using the Snellen chart. Visual impairment was classified into low vision and blindness. The Short Portable Mental Status Questionnaire (SPMSQ) was selected to measure cognitive decline. The confounding factors including age, sex, sociodemographic factors: living status, marital status, education level, health behaviors: smoking, alcohol consumption, betel nut chewing, and physical comorbidities: BMI, hypertension, diabetes, cholesterol and triglyceride were collected for analysis. We recruited 105,208 participants and 4542 (4.3%) have abnormal SPMSQ. The abnormal SPMSQ had significantly higher prevalence of low vision (44.52% vs 18.79%) and blindness (8.89% vs 0.93%) compared with normal SPMSQ. The hazard ratios of abnormal SPMSQ in low vision and blindness were 2.34 (95% CI 2.17-2.52), and 5.13 (95% CI 4.50-5.85), after adjustment for confounders. In conclusion, visual impairment was independently and significantly associated with greater incident cognitive decline among elderly Asian people. Prevention of visual impairment may help to reduce the incidence of cognitive decline in the aged Asian population., (© 2021. The Author(s).)

Burden of COVID-19 on Hospitals across the globe is enormous and has clinical and economic implications. In this retrospective study including consecutive adult patients with confirmed SARS-CoV-2 who were admitted between 3/2020 and 30/9/20, we aimed to identify post-discharge outcomes and risk factors for re-admission among COVID-19 hospitalized patients. Mortality and re-admissions were documented for a median post discharge follow up of 59 days (interquartile range 28,161). Univariate and multivariate analyses of risk factors for re-admission were performed. Overall, 618 hospitalized COVID-19 patients were included. Of the 544 patient who were discharged, 10 patients (1.83%) died following discharge and 50 patients (9.2%) were re-admitted. Median time to re-admission was 7 days (interquartile range 3, 24). Oxygen saturation or treatment prior to discharge were not associated with re-admissions. Risk factors for re-admission in multivariate analysis included solid organ transplantation (hazard ratio [HR] 3.37, 95% confidence interval [CI] 2.73-7.5, p = 0.0028) and higher Charlson comorbidity index (HR 1.34, 95% CI 1.23-1.46, p < 0.0001). Mean age of post discharge mortality cases was 85.0 (SD 9.98), 80% of them had cognitive decline or needed help in ADL at baseline. In conclusion, re-admission rates of hospitalized COVID-19 are fairly moderate. Predictors of re-admission are non-modifiable, including baseline comorbidities, rather than COVID-19 severity or treatment., (© 2021. The Author(s).)

Misokinesia--or the 'hatred of movements'--is a psychological phenomenon that is defined by a strong negative affective or emotional response to the sight of someone else's small and repetitive movements, such as seeing someone fidget with a hand or foot. Among those who regularly experience misokinesia sensitivity, there is a growing grass-roots recognition of the challenges that it presents as evidenced by on-line support groups. Yet surprisingly, scientific research on the topic is lacking. This article is novel in systematically examining whether misokinesia sensitivity actually exists in the general population, and if so, whether there is individual variability in the intensity or extent of what sensitivities are reported. Across three studies that included 4100 participants, we confirmed the existence of misokinesia sensitivity in both student and non-student populations, with approximately one-third of our participants self-reporting some degree of sensitivity to seeing the repetitive, fidgeting behaviors of others as encountered in their daily lives. Moreover, individual variability in the range and intensity of sensitivities reported suggest that the negative social-affective impacts associated with misokinesia sensitivities may grow with age. Our findings thus confirm that a large segment of the general population may have a visual-social sensitivity that has received little formal recognition., (© 2021. The Author(s).)

Disproportionately enlarged subarachnoid space hydrocephalus (DESH) is the characteristic feature of idiopathic normal pressure hydrocephalus. We aimed to characterize the prevalence, development, and association of DESH to cognitive deficit in a large population. We reviewed the data of 1384 subjects eligible for the present study among 1590 participants who underwent magnetic resonance imaging (MRI) in the Ohasama Study, a population-based study in Ohasama, Japan. The participants with Mini-Mental State Examination (MMSE) score <  = 25 were assumed to have cognitive deficit and DESH was evaluated by reviewing the MRIs. We assessed the association between DESH, Evans index (EI), and cognitive deficit using multivariate logistic regression models adjusted for relevant confounders. Furthermore, we evaluated the new development of DESH and the deterioration of cognitive function in the participants with DESH. There were nine participants with DESH (0.65%), seven of whom showed cognitive deficit. DESH was significantly associated with cognitive deficit in multivariate regression analyses (odds ratio; 8.50 [95% confidence interval: 1.61-44.88]). In the 669 participants who underwent follow-up MRI, we found four participants newly presenting with DESH; the development of DESH was observed before/after the presence of EI > 0.3. We also found two participants with existing DESH showing no remarkable worsening in MMSE and EI. The present study demonstrated a positive association between the presence of DESH and cognitive deficit. DESH can develop independently of EI > 0.3, and ventricular enlargement in combination with DESH may be an important factor in the worsening of cognitive deficit., (© 2021. The Author(s).)

We test the hypothesis that endothelial cells adopt an inflammatory phenotype in functionally intact aged human subjects with radiographic evidence of white matter hyperintensity (WMH) suggestive of small cerebrovascular disease. Components of all three complement effector pathways and regulatory proteins were quantified in extracts of plasma endothelial-derived exosomes (EDE) of 11 subjects (age 70-82) with and 15 without evidence of WMH on MRI. Group differences and associations with plasma markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling. EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of some complement components demonstrated significant associations with cognitive slowing and elevated systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Plasma inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several complement components. These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter disease, age-associated cognitive changes, and brain degeneration in functionally normal older individuals. Future endothelial biomarker development may permit recognition of early or preclinical stages of vascular contributions to cognitive impairment and dementia., (© 2021. The Author(s).)

Normative modelling is an emerging method for quantifying how individuals deviate from the healthy populational pattern. Several machine learning models have been implemented to develop normative models to investigate brain disorders, including regression, support vector machines and Gaussian process models. With the advance of deep learning technology, the use of deep neural networks has also been proposed. In this study, we assessed normative models based on deep autoencoders using structural neuroimaging data from patients with Alzheimer's disease (n = 206) and mild cognitive impairment (n = 354). We first trained the autoencoder on an independent dataset (UK Biobank dataset) with 11,034 healthy controls. Then, we estimated how each patient deviated from this norm and established which brain regions were associated to this deviation. Finally, we compared the performance of our normative model against traditional classifiers. As expected, we found that patients exhibited deviations according to the severity of their clinical condition. The model identified medial temporal regions, including the hippocampus, and the ventricular system as critical regions for the calculation of the deviation score. Overall, the normative model had comparable cross-cohort generalizability to traditional classifiers. To promote open science, we are making all scripts and the trained models available to the wider research community., (© 2021. The Author(s).)