Addenbrooke's Cognitive Examination-Revised Research Articles

Lifestyle for brain health and cognitive functioning in midlife to early late-life New Zealanders: Utility of the LIBRA index.

There is enormous potential to improve brain health and reduce the risk of cognitive decline and dementia based on modifiable risk factors. The Lifestyle for Brain Health (LIBRA) index was developed to quantify modifiable dementia risk or room for brain health improvement. The objective of the study was to investigate the utility of the LIBRA index in relation to cognitive functioning in a midlife to early late-life sample of New Zealanders. A subsample (n=1001) of the longitudinal New Zealand Health, Work and Retirement (NZHWR) study completed face-to-face cognitive assessments using the 'Kiwi' Addenbrooke's Cognitive Examination-Revised (ACE-R)in 2010 and again in 2012, in addition to completing biennial NZHWR surveys on socioeconomic, health and wellbeing aspects. The LIBRA index was calculated incorporating information on 8 out of 12 modifiable health and lifestyle factors for dementia. Unadjusted and adjusted regression models and mixed effects models were used to inspect associations of LIBRA with cognitive functioning, cognitive impairment, and cognitive decline. The analytical sample (n=881 [88.0%], after considering exclusion criteria and missing data) had a mean age of 63.1 (SD=6.5) years, 53.3% were female, 26.2% were Māori, and 61.7% were highly educated. Higher LIBRA scores (indicating higher modifiable dementia risk) were associated with lower cognitive functioning (B=-0.33, 95% CI=-0.52;-0.15, p<0.001) and a higher likelihood of cognitive impairment (OR=1.22, 95% CI=1.04; 1.42, p=0.013), but did not predict cognitive decline over 2years (B=-0.03, 95% CI=-0.22; 0.16, p=0.766), adjusted for age, age2, gender, education, and ethnicity. The LIBRA index indicated promising utility for quantifying modifiable dementia risk in midlife and early late-life New Zealanders. For local use, refinement of the LIBRA index should consider cultural differences in health and lifestyle risk factors, and further investigate its utility with a wider range of modifiable factors over a longer observation period.

Association between serum apolipoprotein E and cognitive function in Chinese patients with temporal lobe epilepsy

ObjectiveTo investigate the effect of serum apolipoprotein E (APOE) levels on cognitive function in patients with temporal lobe epilepsy (TLE). MethodsClinical data were collected from 190 subjects including 110 TLE patients and 80 healthy people. Cognitive function was assessed using the Addenbrooke’s Cognitive Examination Revised (ACE-R) scale. Serum levels of APOE were measured using ELISA kits. Genotyping of APOE in peripheral blood was detected by microarray hybridization. ResultsPatients with TLE had significantly lower ACE-R total score, memory and verbal fluency scores compared to the healthy group. Serum levels of APOE were significantly higher in TLE patients than in the healthy subjects. Serum APOE levels were significantly negatively correlated with ACE-R total score, memory and verbal fluency scores. The cognitive function score of TLE with APOE ε4 allele was lower than that of TLE without APOE ε4 allele. SignificanceOur study showed that serum APOE levels were higher in TLE patients than in the healthy population. And serum APOE levels were associated with cognitive dysfunction in TLE patients. APOE ε4 allele carriers have poor cognitive function in TLE patients.

SERUM TRANSTHYRETIN LEVEL IS ASSOCIATED WITH COGNITIVE FUNCTION IN COMMUNITY-DWELLING OLDER ADULTS

Abstract Serum transthyretin (TTR) level has been shown in several studies to be associated with mild cognitive impairment (MCI) and dementia. This study aims to clarify the usefulness of TTR as a biomarker of change in cognitive function in people with normal cognitive function (NC) as a phenotype. We therefore investigate the relationship between cognitive scores and TTR in a cross-sectional study. A longitudinal study then examines the involvement of TTR level in the transition from NC to MCI. Cognitive function was evaluated using Addenbrooke’s Cognitive Examination-Revised (ACE-R). A cross-sectional study was conducted in community-dwelling older people (n=211) classified into NC, MCI, or dementia by ACE-R score. A 32-month longitudinal study was then conducted (n=29). Multiple regression analysis used sex, age, years of education and TTR as dependent variables and ACE-R scores as an independent variable. TTR was significantly associated with ACE-R in people with NC (β = -0.295, p =0.0008). No association with TTR was found in the MCI or dementia groups. Multiple regression analysis using sex, age and each ACE-R subdomain as dependent variables and TTR level as independent variable showed significant association with memory and language. In the longitudinal study, data analysis revealed that TTR level at baseline in females with MCI was significantly higher than it in females with NC. Our results suggest serum TTR levels might be a useful marker for cognitive function in preclinical AD. Elevated TTR might be a predictor of transition to MCI in old-aged adults with NC.

Shorter Reperfusion Time in Stroke is Associated with Better Cognition.

Cognitive changes that result from cerebrovascular disease contribute to a poor functional outcome with reduced quality of life. Among patients undergoing endovascular therapy (EVT), we aim to assess cognitive function and evaluate the impact of reperfusion time in cognitive performance. Patients with acute right anterior circulation strokes that underwent EVT between January 2018 and August 2020 at Centro Hospitalar de Vila Nova de Gaia/Espinho, participated in the study. Modified treatment in cerebral infarction (mTICI) assessed the level of recanalization. Cognitive evaluation was assessed with Addenbrooke's Cognitive Examination revised (ACE-R). Multiple linear regression analyses were used to determine the association between time for recanalization and ACE-R. The level of significance adopted was 0.05. The mean age of participants was 71.5 (interquartile range [IQR] 62.0-78.2) years, and 50% (22) were women. The median time after stroke was 28.6 months (IQR 18.94-31.55). All patients in our sample had a successful level of recanalization with EVT (mTICI ≥ 2b). Time for recanalization showed an inverse association with the ACE-R (b = -0.0207, P = 0.0203). Also the mRS at 3 months had an inverse association with cognition (b = -5.2803, p = 0.0095). Level of education had a strong and direct relationship with ACE-R results (b = 3.0869, p < 0.0001). Longer time between stroke symptoms and recanalization with EVT in patients with right hemisphere ischemic stroke lead to lower ACE-R scores. Measures to improve door-to-recanalization time are also important for cognitive performance after ischemic stroke.

Post-COVID-19 Cognitive Decline and Apoe Polymorphism: Towards a Possible Link?

APOE ε4 polymorphism has been recently described as a possible association with cognitive deficits in COVID-19 patients. This research aimed to establish the correlation between COVID-19 and cognitive impairment, and the APOE gene polymorphism among outpatients. We performed a cross-sectional study with confirmed COVID-19 patients and neurological symptoms that persisted for more than three months from onset. APOE genotypes were determined. The final number of patients included in this study was 219, of which 186 blood samples were collected for APOE genotyping, evaluated 4.5 months after COVID-19. Among the participants, 143 patients (65.3%) reported memory impairment symptoms as their primary concern. However, this complaint was objectively verified through screening tests (Addenbrooke Cognitive Examination-Revised and Mini-Mental State Examination) in only 36 patients (16.4%). The group experiencing cognitive decline exhibited a higher prevalence of the APOE ε4 allele than the normal group (30.8% vs. 16.4%, respectively, p = 0.038). Furthermore, the APOE ε4 allele and anxiety symptoms remained significant after multivariate analysis. This study assessed an outpatient population where cognitive changes were the primary complaint, even in mild cases. Moreover, the ε4 allele, sleep disorders, and anxiety symptoms were more frequent in the cognitive decline group.

Depressive symptoms associated with brain morphometry in Mild Cognitive Impairment stage due to Alzheimer’s and Parkinson’s disease

Objectives: Although there are studies linking depressive symptoms with psychiatric diseases, and then, with brain morphometry, scarce is the literature examining the association between depressive symptoms and brain morphometry in the prodromal stage of neurodegenerative disorders. In the current analysis, we used a fair sample of Mild Cognitive Impairment (MCI) stage due to Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients, to examine the association between different depressive symptoms and a large variety of brain morphometric factors.&#x0D; Methods/ Design: Our sample consisted of 352 patients. The Geriatric Depression Scale (GDS) was used for the association with brain measurements. Principal Components Analysis (PCA) and regression models were used for the analyses. Age, sex, years of education, Addenbrooke’s cognitive examination revised (ACE-R), and estimated total intracranial volume were used as covariates.&#x0D; Results: Factor3 was significantly and positively correlated with GDS total, Dysthymia, Anxiety and Hopelessness. r_factor1, r_factor2 and r_factor5 were significantly and positively correlated with Anxiety, while r_factor5 was also correlated with GDS total. Concerning volumes, v_factor3 was found to be correlated with GDS total, Dysthymia, Anxiety and Hopelessness.&#x0D; Conclusions: The association between depressive symptoms and upcoming neurodegenerative disorders is reflected in human brain structural alterations, suggesting specific modifications in network-like patterns and neuronal connectivity. Characterizing differences in the morphometry of brain regions among MCI patients with depressive symptoms may aid the early diagnosis and treatment of these symptoms.

Influence of Mobile Application Based Brain Training Program on Cognitive Function and Quality of Life in Patients Post Stroke

Background: Stroke often leads to cognitive impairment, which can significantly reduce one's independence as well as quality of life. Cognitive rehabilitation is a treatment strategy for restoring cognitive abilities following brain injuries. Cognitive functioning can be improved through the use of multimedia as well as informatics in computerized cognitive rehabilitation (CCR). Purpose: to investigate the influence of a mobile application-based brain training program on cognitive functions as well as quality of life in post stroke patients. Methodology: forty referred medically and radiologically diagnosed stroke patients from both genders experienced post stroke cognitive impairment (PSCI), aged from 45 to 60 years old, were randomized into two groups of the same number: a study group and a control group. The Study group received mobile application-based brain training program (Lumosity training application) as well as aerobic training on a bicycle ergometer, and the control group received only the aerobic training on a bicycle ergometer for 18 sessions every other day for 6 weeks, 3 sessions/week, each session for 60 minutes. All patients were evaluated with Computer-based cognitive device RehaCom, Addenbrooke’s Cognitive Examination Revised (ACE-R) test, Montreal Cognitive Assessment (MoCA) in addition to Stroke specific quality of life scale (SS-QoL) pre and post treatment. Results: a significant difference has been detected among the two groups as the (p-value = 0.001) indicating that the study group reported enhancement in the cognitive functions as well as the quality of life more than the control group and there was a correlation between RehaCom, MoCA, ACE-R and SS-QoL. Conclusion: This study showed that six weeks of mobile application-based brain training program (Lumosity training application) as well as aerobic training on a bicycle ergometer was a beneficial approach and is a successful treatment for patients suffering from (PSCI).

Serum transthyretin level and its relationship with cognitive function in community-dwelling older people: Cross sectional and longitudinal study

BackgroundSerum transthyretin (TTR) level has suggested association with mild cognitive impairment (MCI) and dementia. To clarify its usefulness as a biomarker of change in cognitive function in older individuals with normal cognitive function (NC) as a phenotype, we investigated the relationship between cognitive scores and TTR levels. We also investigated the involvement of TTR in the transition from NC to MCI. MethodsCognitive function was evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R). A cross-sectional study was conducted in community-dwelling older people (n = 211) with NC, MCI, or dementia according to ACE-R scores. A 32-month longitudinal study was then conducted (n = 29). ResultsMean TTR levels did not differ between the NC, MCI and dementia groups. Linear regression analysis showed a significant relationship in people with NC between TTR and ACE-R (β = -0.192; p < 0.001). Multiple regression analysis adjusted for stepwise procedure-selected covariates showed that TTR was significantly associated with ACE-R in people with NC (β = -0.130; p = 0.014). Furthermore, multiple regression analysis showed significant association between TTR level and memory (β = -0.584; p = 0.002) and with language (β = -0.743; p = 0.031) in people with NC. In the longitudinal study, mean TTR level at baseline in women with MCI was significantly higher than that in women with NC (p = 0.044). ConclusionsSerum TTR level is suggested to be associated with cognitive scores in people with NC and to be an indicator of progression from NC to MCI.

Using MemTrax memory test to screen for post-stroke cognitive impairment after ischemic stroke: a cross-sectional study.

Whereas the Montreal Cognitive Assessment (MoCA) and Addenbrooke's cognitive examination-revised (ACE-R) are commonly used tests for the detection of post-stroke cognitive impairment (PSCI), these instruments take 10-30 min to administer and do not assess processing speed, which is a critical impairment in PSCI. MemTrax (MTx) is a continuous recognition test, which evaluates complex information processing, accuracy, speed, and attention, in 2 min. To evaluate whether MTx is an effective and practical tool for PSCI assessment. This study enrolled acute ischemic stroke (AIS) patients who have assessed the cognitive status including MTx, clinical dementia rating (CDR), MoCA, Neuropsychiatric Inventory (NPI), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), the National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), and Barthel Index of activity of daily living (BI) combined with the physical examinations of the neurologic system at the 90-day (D90) after the AIS. The primary endpoint of this study was establishing MTx cut-offs for distinguishing PSCI from AIS. Of the 104 participants, 60 were classified to the PSCI group. The optimized cut-off value of MTx-%C (percent correct) was 78%, with a sensitivity and specificity for detecting PSCI from Non-PSCI of 90.0 and 84.1%, respectively, and an AUC of 0.919. Regarding the MTx-Cp (Composite score = MTx-%C/MTx-RT), using 46.3 as a cut-off value, the sensitivity and specificity for detecting PSCI from Non-PSCI were 80.0 and 93.2%, with an AUC of 0.925. Multivariate linear regression showed that PSCI reduced the MTx-%C (Coef. -14.18, 95% CI -18.41∼-9.95, p < 0.001) and prolonged the MTx-RT (response time) (Coef. 0.29, 95% CI 0.16∼0.43, p < 0.001) and reduced the MTx-CP (Coef. -19.11, 95% CI -24.29∼-13.93, p < 0.001). MemTrax (MTx) is valid and effective for screening for PSCI among target patients and is a potentially valuable and practical tool in the clinical follow-up, monitoring, and case management of PSCI.

Neurocognitive Disorders in HIV-positive Patients.

(1) To know the prevalence of HAND in HIV-infected patients of a multi-ethnic population. (2) To describe various types of neurocognitive impairment among patients of HAND and study the factors affecting HAND. This study was a cross-sectional descriptive study conducted on 250 HIV-positive patients in outpatient department (OPD) of a tertiary care center in Mumbai, conducted over a period of 12 months. Patients with HIV-1 attending the OPD and having a minimal formal education of 4 years were included. Patients with concomitant delirium, any known central nervous system (CNS) disorder, any psychiatric disorder, and pregnant females were excluded. Outcome measures-the test batteries used were (1) International HIV Dementia Scale (IHDS) and (2) Addenbrookes cognitive examination-revised (ACE-R) scale. Of 250 subjects studied, 55.6% (139) were males and 44.4 % (111) were females. The mean age of study population was 39.42 years. The mean years of education were 8.32 years. The mean duration of infection (diagnosis of HIV-positive state) was 64.49 months and the mean duration of HAART intake in our patients was 52.30 months. The mean cluster of differentiation 4 (CD4) counts of our subjects were 527.13 per cumm [standard deviation (SD) of 234.13]. The mean nadir CD4 counts were 224.35 per cumm (SD of 115.09). Using the ACE-R scale, the prevalence of HAND was 71.60%, of which 37.20% had an asymptomatic neurological impairment, 29.60% had mild cognitive dysfunction, and 4.80% had HAD. Memory, verbal fluency and visuospatial abilities were the most affected domains on the ACE-R and memory recall and psychomotor speed were affected more on the IHDS. The prevalence of HAND was more with increasing age (p = 0.020), lesser education (p &lt; 0.00) and lesser nadir CD4 counts (p &lt; 0.00). However, it was not affected by the duration of the disease and the current CD4 counts (p &gt; 0.05). Human immunodeficiency viruses (HIV) associated neurocognitive disorders HAND is common in HIV-positive patients, most of whom are asymptomatic. Older patients with less education and severe disease, having lower nadir counts are at the highest risk of HAND. Memory, verbal fluency, and visuospatial abilities were the most commonly affected domains.

Predicting Dementia Due to Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia Using Algorithms with the Addenbrooke's Cognitive Examination-Revised Subscores Combined with Sociodemographic Factors.

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are important causes of dementia with challenging differential diagnoses in many cases. Addenbrooke's Cognitive Examination-Revised (ACE-R) is a cognitive battery that may be useful to differentiate the two disorders. The objectibe of this study is to investigate the value of the ACE-R combined with sociodemographic factors in the differential diagnosis between AD and bvFTD. The ACE-R was administered to 102 patients with mild dementia due to probable AD, 37 with mild bvFTD, and 135 controls. Performances of patients and controls were analyzed by logistic regression and by ROC curves to refine the diagnostic accuracy of the ACE-R in AD and bvFTD. The ACE-R subscores Attention and Orientation, Fluency, and Memory, in combination with schooling differentiated AD from controls with an area under the ROC curve (AUC) of 0.936 (86% sensitivity and 87% specificity). The ACE-R subscores Attention and Orientation, Fluency, and Language, in combination with sex (male), age, and schooling, discriminated bvFTD from controls with an AUC of 0.908 (81% sensitivity and 95% specificity). In the differentiation between AD and bvFTD, the ACE-R subscores Attention and Orientation, Fluency, and Language, together with age, displayed an AUC of 0.865 (78% sensitivity and 85% specificity). The combination of ACE-R scores with sociodemographic data allowed good differentiation between AD and bvFTD in the study sample.

Outcomes of a Cognitive Management Program (CMP) for an Individual with Mild Neurocognitive Disorder at Risk of Developing Alzheimer

Individuals with mild neurocognitive disorder (mild-NCD) may suffer from one or a range of mild neurocognitive dysfunctions that disturb their daily life routines. This study tested the outcomes of an author-compiled cognitive management program (CMP) on a patient at the risk of developing Alzheimer. The CMP comprised a careful diagnostic procedure, a multi-dimensional cognitive assessment of the participant's cognitive functioning, and a series of cognitive rehabilitation procedures. A 59-year old woman (diagnosed based on DSM-5 and Addenbrooke’s Cognitive Examination-Revised (ACE-R)) was included in the study. The participant's cognitive rehabilitation program consisted of a face-to-face training for twelve sessions and a daily homework-based training (35 days). The participant was tested at the baseline, at the end of the rehabilitation procedure, and 6- and 12-month follow-ups. To measure memory, attention, executive function, language, and reasoning abilities the following tests were administered: (a) Forward and Backward Digit Span Test; (b) Rey Complex Figure Test; (c) Continuous Performance Test; (d) Color-Word Interference; (e) Verbal Fluency; (f) Trial Making Test; (g) Symbol Digit Modality Test; and (h) The Twenty Questions Test and the Word Context Test. The Mean Percentage Improvement (MPI) index suggested improvements in the participant's scores for ACE-R subscales, memory, attention, language, executive functions, and reasoning and persistent improvements in the Word Context Test (55% at post-test and 63% at follow-up) and Rey Complex Figure Test (33% at the post-test and 47% at the follow-up). The results suggest that the CMP could improve the overall cognitive functioning of the participant.

Neuropsychological tests and prediction of dementia in association with the degree of carotid stenosis.

This study constitutes a cross sectional analysis of the association between cognitive impairment defined by neuropsychological tests and carotid stenosis. The main objective was to compare the results of the Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination-Revised (ACE-R) with regard to the degree of carotid stenosis. The sample comprised 744 patients who underwent a carotid duplex ultrasound and cognitive function testing (by ACE-R and MMSE). A multivariable analysis of potential confounding factors was completed. The significance of the different number of positive (MMSE ≤ 27, ACE-R ≤ 88) and negative (MMSE ≥ 28, ACE-R ≥ 89) results of the neuropsychological tests was analysed with regard to the degree of carotid stenosis (50-99%). Neuropsychological test results were also compared between carotid stenosis of 50-69%, 70-89%, and 90-99%. For both the MMSE and ACE-R, a difference was observed between positive and negative test results when higher degrees of stenosis were present. However, for the ACE-R only, more severe stenosis (80-89%, 90-99%) was predominantly associated with positive test results (p-value < 0.017). The same dependence for ACE-R (although not statistically significant) was observed in the group of patients without an ischemic stroke (confounding factor). In the case of the MMSE and more severe stenosis, negative results predominated, regardless of the confounding factor. There were no statistically significant differences in test results between carotid stenosis of 50-69%, 70-89%, and 90-99%. The results suggest that for assessing the early risk of cognitive impairment in patients with carotid atherosclerosis, the ACE-R appears more suitable than the MMSE.

Cognitive impairment one year after hospitalization due to COVID‐19 infection in Brazil: preliminary results.

AbstractBackgroundPersistence of symptoms or development of new symptoms after SARS‐CoV‐2 infection is an increasingly recognized problem and the long‐term post‐COVID‐19 outcome and the effects on cognitive function remain poorly understood. This study aims to investigate the long‐term cognitive effects and impacts of COVID‐19 with a special focus on a population with low education and low socioeconomic status.MethodCross‐sectional cognitive assessment of participants with severe forms of Covid‐19 one year after hospital admission. Until now, 187 of 322 patients underwent TICS‐M for brief telephone cognitive screening one year after hospitalization for COVID‐19 in 3 public hospitals in Belo Horizonte, Brazil. This sample was divided into two groups according to scores on the TICS‐M screening test: with or without cognitive impairment. 26 participants were selected by convenience for neuropsychiatric assessment, namely 13 with abnormal TICS‐M scores (cases) and the other 13 controls. They were submitted to the following tests and scales: Addenbrooke’s Cognitive Examination‐Revised (ACE‐R), Symbol Digit Modalities Test (SDMT), Free and Cued Selective Reminding Test (FCSRT‐IR), Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale‐Revised (IES‐R).ResultThere were no significant differences between groups for age, sex, educational level, need for intensive care unit or use of anticholinergics or sedatives. Although the comparison of SDMT between the groups showed no statistical difference (p = 0.999), all participants showed lower performance compared to normative data. Cases presented lower scores than controls in ACE‐R total (p = 0.034) and in the subdomains Attention and Orientation (p = 0.002), as well as in delayed total recall of the FCSRT‐IR (p = 0.039). Moreover, participants with lower HAD‐D scores had worst performance in Attention and Orientation subdomains of the ACE‐R (p = 0.003).ConclusionOur study shows impairment in global cognition, attention, orientation and episodic memory in individuals previously hospitalized for COVID‐19 infection who presented low scores on TICS‐M. Performance in processing speed tests was impaired among both groups in relation to normative data. Cognitive and mood analyses after COVID‐19 infection can provide information for improving healthcare of these individuals.

Impact of Sociodemographic Features and Lifestyle on Cognitive Performance of Peruvian Adults.

Cognitive impairment and dementia may result from a combination of modifiable and nonmodifiable risk and protective factors, such as the environment, educational attainment, time devoted to cognitively stimulating activities, and physical activity. This study aimed to investigate the mediating role of sociodemographic characteristics and lifestyle factors in the years of education and cognitive performance in Peruvian adults. This cross-sectional study included 1,478 subjects assessed by Addenbrooke's Cognitive Examination Revised (ACE-R). Using mediation models, we evaluated the mediation role of parents' educational level, reading time (RT), and physical activity time (PAT) in the years of education (IYE) and cognitive performance. People who reported having lived in an urban area during their childhood are estimated to have, on average, 2.085 years more formal education than those who lived in rural areas. In addition, 49% of cognitive performance scores are explained by the mediation effect of reading and physical activity time in the IYE. This implies that higher levels of education, mediated by RT and PAT per week, are 1.596 units associated with higher scores on the ACE-R. Despite the fact that nonmodifiable factors (i.e., childhood residence area, parents' educational level) seem to exert an effect on older adults' cognition, their influence is mediated by other factors that are indeed modifiable (i.e., reading time, physical activity engagement). In this sense, lifestyle changes could help prevent or decrease the risk of cognitive impairment and reduce the disease's impact on vulnerable environments in Latin American and Caribbean countries.

211 ASSOCIATION OF PLASMA ANTIOXIDANTS AND COGNITIVE OUTCOMES IN NORTHERN IRISH MEN FROM PROSPECTIVE EPIDEMIOLOGICAL STUDY OF MYOCARDIAL INFARCTION (PRIME) STUDY

Abstract Background Oxidative stress and chronic inflammation have been demonstrated to contribute to cognitive decline in older age and the development of neurodegenerative disorders. Antioxidants have been revealed to help mitigate the effects of the damage caused by oxidative stress and inflammation, but their relationship with cognitive decline is not yet fully understood. The aim of this study was to investigate the association between various plasma antioxidant levels and cognitive status in participants from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study. Methods 10,600 men were recruited to the PRIME study between 1991-1993 and have been followed up across eleven time points. Baseline health and lifestyle characteristics were assessed, and plasma antioxidants were obtained and quantified. Baseline cognitive status was screened in 2000 using Mini-Mental State Examination (MMSE). Follow up assessment of cognitive status was performed in 2015 with MMSE and Addenbrooke’s Cognitive Examination-Revised (ACE-R) examinations. Results 2,009 men underwent cognitive assessment in 2000 and 873 men in 2015. At both 2000 and 2015 with the use of the MMSE and ACE-R examinations to assess cognitive status, serum concentration of all the antioxidants except for gamma-tocopherol and lycopene were higher in the men with better cognitive performance at a significant level of p&amp;lt;0.05. Better cognitive performance was associated with more time spent in education and higher level of education achieved at a statistically significant level (p&amp;lt;0.01). Furthermore, those with cognitive impairment were more likely to be older. After adjustments for lifestyle variables with a linear regression model, the only significant variable associated with cognition was time spent in education (B = 0.521, p= 0.02). Conclusion The findings suggest that the concentration of plasma antioxidants is associated with cognitive status. Smoking and education, as well as other lifestyle factors were, demonstrated to have an impact on cognitive status.

Frequency and risk factors for cognitive dysfunction in peritoneal dialysis patients.

There is limited data on cognition in patients undergoing peritoneal dialysis (PD). We assessed prevalence and associated risk factors of neurocognitive impairment (NCI) in PD patients. A cross-sectional cohort study of 149 PD patients at a single centre between 2016 and 2020 who underwent neurocognitive screening at defined intervals by Addenbrooke's Cognitive Examination - Revised (ACE-R) with incorporated Mini-Mental State Examination (MMSE). Paired-sample t-test was used to compare cognitive performance to the general population and compare cohorts for dichotomous risk factors. Residual renal function (RRF) and clearance kinetics were evaluated using local regression models. Sub-analysis was performed in patients with cerebrovascular disease (CVD). Patients on PD performed poorly in ACE-R screening compared to population norms, with discrepancy in all cognitive domains. In patients without CVD, attention and language domains were comparable to norms. The MMSE detected cognitive impairment in 2% of studied patients, significantly fewer than when the ACE-R was applied (32%). Age, gender, diabetic status and depression were associated with lower neurocognitive screening performance (p < .05). Dialysis vintage beyond 12 months conferred poorer cognitive performance. RRF correlated with cognitive performance. Patients on PD have higher prevalence of NCI than the general population, primarily with impairments in memory, fluency and visuospatial reasoning. CVD confers poorer performance in attention and language domains. The MMSE is ineffective in detecting subtle NCI in this population compared with ACE-R. Risk factors for NCI include age, gender, diabetic status, depression and vintage beyond 12 months. Protective factors include RRF.

Lymphocyte Count and Neutrophil-to-Lymphocyte Ratio Are Associated with Mild Cognitive Impairment in Parkinson's Disease: A Single-Center Longitudinal Study.

Lymphocyte count and neutrophil-to-lymphocyte ratio (NLR) may represent useful biomarkers of Parkinson’s disease (PD), but their role in PD-related mild cognitive impairment (MCI) has not been fully elucidated. The present study aimed to confirm whether these immunological measures can discriminate PD patients from healthy controls (HC) and establish their feasibility as prognostic biomarkers of MCI in PD. Immunological data at baseline were analyzed in 58 drug-naïve PD patients and 58 HC matched 1:1 for age, sex, and cardiovascular comorbidities. We selected a subgroup of 51 patients from this initial cohort who underwent longitudinal neuropsychological assessments through the Addenbrooke’s Cognitive Examination Revised (ACE-R) test. We considered the last examination available to analyze the relationship between ACE-R test scores and immunological measures. We found that lymphocyte count was lower and NLR higher in PD than HC (p = 0.006, p = 0.044), with AUC = 0.649 and 0.608, respectively. Secondly, in PD-MCI there were significantly higher levels of circulating lymphocytes (p = 0.002) and lower NLR (p = 0.020) than PD with normal cognitive status (PD-NC). Correlations between lymphocyte count and ACE-R total score and memory subitem (r = −0.382, p = 0.006; r = −0.362, p = 0.01), as well as between NLR and ACE-R total score and memory subitem (r = 0.325, p = 0.02; r = 0.374, p = 0.007), were also found. ROC curve analysis showed that lymphocyte count and NLR displayed acceptable discrimination power of PD-MCI with AUC = 0.759 and 0.691, respectively. In conclusion, we suggest that an altered peripheral immune phenotype could foster cognitive decline development in PD, thus opening the possibility of immune-targeting strategies to tackle this disabling non-motor feature.

Association between Vitamin D and Cognitive Deficiency in Alcohol Dependence.

There are still not enough findings to elucidate how exactly alcohol use impairs cognitive abilities. Some studies have shown that there is a link between alcohol intake and vitamin D levels, but these findings are inconsistent so further research is needed. The aim of this study was to investigate the association between serum vitamin D levels and cognitive impairment in alcohol-dependent individuals. A case-control study was carried out including a total of N = 132 respondents with a medical history of alcoholism, and healthy volunteers. The Montreal Cognitive Assessment (MoCa) and Addenbrooke’s Cognitive Examination-Revised (ACE-R) screening tools were used for cognitive status assessment and serum vitamin D levels analysis (blood samples of respondents). Significant difference (p = 0.022), was found in vitamin D levels in the alcohol-dependent group with cognitive deficiency 13.7 ± 9.4 (ng/mL), alcohol-dependent group without cognitive deficiency 19.5 ± 11.2 (ng/mL) and healthy controls 19.9 ± 11.1 (ng/mL), respectively. Furthermore, vitamin D levels were significantly different across all groups based on MoCa (p = 0.016) and ACE-R (p = 0.004) scores. All three groups exhibited vitamin D deficiency. A significant correlation was found between vitamin D deficiency and cognitive impairment, but it yielded no significant difference in alcohol-dependent individuals.

Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial.

SummaryBackgroundDementia greatly contributes to poor prognosis in patients with Parkinson's disease (PD). We previously reported that severe olfactory dysfunction may be a good predictor of Parkinson's disease dementia (PDD). In this trial, we investigated whether early administration of donepezil to patients with severe hyposmia can reduce the development of PDD.MethodsThis was a multi-centre, randomized, double-blind, parallel group, placebo-controlled trial in patients with non-demented PD with severe hyposmia (The Donepezil Application for Severe Hyposmic Parkinson's Disease [DASH-PD] study). A total of 201 patients were randomly allocated to receive donepezil or placebo in addition to standard therapy for PD. Patients were followed up every 6 months until the onset of PDD or for a maximum of 4 years. The primary endpoint was the onset of dementia. The secondary endpoint was cognitive impairment measured by Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Clinical Dementia Rating (CDR).(UMIN000009958: February 2013 to May 2019).FindingsA total of 201 hyposmic patients with PD were randomly assigned to a treatment: 103 to donepezil and 98 to placebo. Overall, 141 (70%) patients completed the 4-year intervention. During follow-up, 7 of 103 (6.8%) patients in the donepezil group and 12 of 98 (12.2%) patients in the placebo group developed PDD; however, the hazard ratio of PDD incidence was not statistically significant (hazard ratio (HR), 0.609; 95% confidence interval, 0.240 to 1.547; p = 0.2969). At week 208, the patients in the donepezil group had better scores on the ACE-R (p < 0.005) and the CDR (p < 0.005) than those taking placebo.InterpretationAdministration of donepezil to PD patients with severe olfactory dysfunction for 4 years did not change the incidence of dementia but had a beneficial effect on neuropsychological function, with good tolerability.FundingThe Ministry of Health Labour and Welfare and the Japan Agency for Medical Research and Development provided funding for this study.