Search

• We found a preponderance of specific seropositivities showed positive trends of association with MCI-dementia. • Dengue and VZV showed significant negative associations with MCI-dementia. • High infection burden was significantly associated with an increased MCI-dementia risk. • For most pathogens, levels of antibody titers were significantly lower in those with MCI-dementia. Infection by pathogenic microbes is widely hypothesized to be a risk factor for the development of neurocognitive disorders and dementia, but evidence remains limited. We analyzed the association of seropositivity to 11 common pathogens and cumulative infection burden with neurocognitive disorder (mild cognitive impairment and dementia) in a population-based cohort of 475 older individuals (mean age = 67.6 y) followed up over 3–5 years for the risk of MCI-dementia. Specific seropositivities showed a preponderance of positive trends of association with MCI-dementia, including for Plasmodium, H. pylori , and RSV (p < 0.05), as well as Chickungunya, HSV-2, CMV and EBV (p > 0.05), while HSV-1 and HHV-6 showed equivocal or no associations, and Dengue and VZV showed negative associations (p < 0.05) with MCI-dementia. High infection burden (5 + cumulated infections) was significantly associated with an increased MCI-dementia risk in comparison with low infection burden (1–3 cumulative infections), adjusted for age, sex, and education. Intriguingly, for a majority (8 of 11) of pathogens, levels of antibody titers were significantly lower in those with MCI-dementia compared to cognitive normal individuals. Based on our observations, we postulate that individuals who are unable to mount strong immunological responses to infection by diverse microorganisms, and therefore more vulnerable to infection by greater numbers of different microbial pathogens or repeated infections to the same pathogen in the course of their lifetime are more likely to develop MCI or dementia. This hypothesis should be tested in more studies. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity is known to positively influence cognitive performance. For adults with mild cognitive impairment (MCI), the relationship between physical activity levels and cognitive performance is unknown. This cross‐sectional study aimed to determine if cognitive performance [as measured by the Montreal Cognitive Assessment (MoCA)] of people living in the community with MCI is associated with their physical activity levels or sedentary behaviour. Methods: ActivPAL™ accelerometers were used to objectively measure physical activity and sedentary behaviour for seven full days. Cognitive performance was measured using the MoCA. Consumer and Community Involvement: No involvement other than as research participants Results: Eighty‐two participants from the Balance on the Brain randomised controlled trial were included. Most participants were retired (88%), with 33 (40%) reporting a fall in the last year. The median MoCA score was 24 (IQR 22–26). Participants achieved a mean of 6296 (±2420) steps per day and were sedentary for 10.6 (±2) hours per day. The only physical activity outcomes that had a fair, positive correlation were moderate‐ to vigorous‐intensity physical activity measures of total stepping time and total number of steps (with a cadence of ≥100 steps/min) with the orientation MoCA domain score (r(82) = 0.36, p ≤ 0.001 and r(82) = 0.37, p ≤ 0.001, respectively). Higher total sedentary time had a weak, positive correlation with better visuospatial/executive performance (r(82) = 0.23, p = 0.041). The orientation outcomes remained significant when analysed in an adjusted logistic regression model. Conclusion: This study found that performance in the MoCA orientation domain had a fair‐positive correlation with moderate‐intensity physical activity (i.e., stepping time and step count with a cadence of ≥100 steps/min) as measured by a thigh‐worn accelerometer for community‐dwelling older adults with MCI. When considering the relationship between cognitive domains and sedentary behaviour, consideration may be needed regarding whether cognitive enhancing activities (such as crosswords and other brain games) are being performed, which may confound this relationship. Further investigation is required to confirm these results. PLAIN LANGUAGE SUMMARY: Physical activity is good for people of all ages. Regular moderate to vigorous physical activity is known to help memory and thinking skills. Moderate physical activity includes brisk walking, lawn mowing and water aerobics. Vigorous physical activity includes running, fast‐paced swimming, cycling and brisk walking up hills and steps. For adults with mild cognitive impairment (i.e., a person who is starting to have trouble with their memory, but the difficulty is not yet advanced enough to be diagnosed as dementia), we did not know how their level of engagement with physical activity may be related to their memory and thinking skills. A strength of this study is that we had a large population of 82 people living in the community with mild cognitive impairment to review. We found that people who completed more moderate to vigorous physical activity had better skills in remembering the current day, date and place (orientation). [ABSTRACT FROM AUTHOR]

This study re-examined the Memory Assessment Scale (MAS), a brief memory test developed in Hawai'i in 1987, to assess whether it remains a valid and reliable cognitive impairment screening tool in Hawai'i. Patients suspected of having neurocognitive dysfunction were divided into 2 groups (those with and without mild cognitive impairment) based on their results on a battery of neuropsychological tests. No differences in MAS scores were found between patients with and without mild cognitive impairment. Further research with the MAS comparing patients with mild cognitive disorder to healthy controls is indicated to further examine the efficacy of this population-based test. [ABSTRACT FROM AUTHOR]

Objectives: To identify falls prevalence, falls risk factors and evaluate the effectiveness of falls prevention interventions for community-dwelling people with Mild Cognitive Impairment. Data sources: Peer-reviewed articles (inception to 4 August 2022) from PubMed, CINAHL, PsycInfo, EMBASE, Scopus, SportDiscus and the Cochrane library. Review methods: All types of methodological approaches were considered. Inclusion criteria were community-dwelling; diagnosis of Mild Cognitive Impairment; aged 50+ years. Interventions needed to include falls prevention programs aiming to reduce falls and/or risk of falls. Outcomes of interest included number and/or rate of falls, falls prevalence and falls risk factors. For controlled trials, any control group was included. Quality assessment was completed using Cochrane's Risk of Bias Tool for randomized controlled trials and the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields for all other studies. Where statistical data pooling was not possible, narrative synthesis was used to present data in tables and figures. Results: Forty-seven studies were included. Prevalence of falls was 43% when data were gathered prospectively for 12 months. Confirmed falls risk factors included slow gait, dual-tasking, postural control and non-amnesic Mild Cognitive Impairment. Few studies evaluated interventions to reduce falls. Six meta-analyses were conducted, no significant reduction in falls was found. Conclusions: Until further high-quality, adequately powered studies are available to guide practice, best practice guidelines recommend balance training as a core component of falls prevention programs for older people generally, as well as people with Mild Cognitive Impairment. [ABSTRACT FROM AUTHOR]

Background: Early intervention of amnestic mild cognitive impairment (aMCI) may be the most promising way for delaying or even preventing the progression to Alzheimer's disease. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been recognized as a promising approach for the treatment of aMCI.Objective: In this paper, we aimed to investigate the modulating mechanism of tDCS on the core neurocognitive networks of brain.Methods: We used repeated anodal high-definition transcranial direct current stimulation (HD-tDCS) over the left dorsolateral prefrontal cortex and assessed the effect on cognition and dynamic functional brain network in aMCI patients. We used a novel method called temporal variability to depict the characteristics of the dynamic brain functional networks.Results: We found that true anodal stimulation significantly improved cognitive performance as measured by the Montreal Cognitive Assessment after simulation. Meanwhile, the Mini-Mental State Examination scores showed a clear upward trend. More importantly, we found significantly altered temporal variability of dynamic functional connectivity of regions belonging to the default mode network, central executive network, and the salience network after true anodal stimulation, indicating anodal HD-tDCS may enhance brain function by modulating the temporal variability of the brain regions.Conclusion: These results imply that ten days of anodal repeated HD-tDCS over the LDLPFC exerts beneficial effects on the temporal variability of the functional architecture of the brain, which may be a potential neural mechanism by which HD-tDCS enhances brain functions. Repeated HD-tDCS may have clinical uses for the intervention of brain function decline in aMCI patients. [ABSTRACT FROM AUTHOR]

Introduction: Mild cognitive impairment (MCI) is defined as the symptomatic pre-dementia phase on the continuum of cognitive decline. Early recognition and application of potential interventions could prevent or delay the progression to dementia. The Rowland Universal Dementia Assessment Scale (RUDAS) shows good performance in the screening of dementia but has limited data regarding its diagnostic properties in the screening of MCI. The objectives of this study were to assess the psychometric properties of the Thai version of the RUDAS (RUDAS-Thai) in the screening of MCI, identify associated factors for the RUDAS performance, and determine the optimal cutoff point in detecting MCI. Methods: This was a cross-sectional study conducted from January 2020 to March 2021. Older patients at the outpatient clinic of an internal medicine department at a tertiary care hospital in Thailand were examined. Baseline data were collected, and the RUDAS-Thai was administered to each patient. Afterward, a geriatrician assessed each patient for MCI. Results: A total of 150 patients were included, of whom 42 cases (28%) had MCI. The overall performance of the test using an area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval 0.75–0.89). At the optimal cutoff point of 25/30, the AUC was 0.76 with sensitivity and specificity of 76.2 and 75%, respectively. The educational level affected the test performance according to regression analysis. For patients with years of education ≤6 and >6, the optimal cutoff points were 25/30 and 26/30, respectively. Conclusion: The RUDAS-Thai performed well in differentiating patients with MCI from normal cognition; however, it was affected by educational level. A score of 25/30 or lower for persons with ≤6 years of education or 26/30 or lower for persons with higher than 6 years of education is the optimal cutoff point for indication of developing MCI.

Abstract Background The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD. Methods A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) completed two Mini-Mental State Examinations (MMSEs) over a 1-year interval. In all 100 participants at the second MMSE, we examined the plasma levels of IL-33, IL-β, IL-1 receptor agonist (IL-1RA), beta amyloid (Aβ), and tau and apolipoprotein E (ApoE) genotyping; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. Results IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P

Background: The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains uninvestigated in clinical studies of Alzheimer's disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD. Methods: A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) completed two Mini-Mental State Examinations (MMSEs) over a 1-year interval. In all 100 participants at the second MMSE, we examined the plasma levels of IL-33, IL-β, IL-1 receptor agonist (IL-1RA), beta amyloid (Aβ), and tau and apolipoprotein E (ApoE) genotyping; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. Results: IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P < 0.001). Patients expressing IL-33 preserved their cognitive function compared with IL-33 non-expressing patients (1-year ΔMMSE, 0.16 ± 1.6 vs − 1.5 ± 2.6; P = 0.006). The cognitive preservation was not associated with the lower levels of Aβ, tau, and ApoE ε4, while higher levels of ApoE ε4 and phosphorylated tau were indeed associated with cognitive decline. The aMCI patients with AD conversion during study period had higher proportion of IL-33(−) than non-AD converters (90.9% vs 53.3%, P = 0.04). Conclusions: IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD. [ABSTRACT FROM AUTHOR]

Background: By the time Alzheimer's disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed.Objective: To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups.Methods: We report on the rationale and describe the design of a multisite randomized controlled trial that aims to prevent ADRD in older persons with: (1) mild cognitive impairment (MCI); (2) remitted major depressive disorder (MDD) without MCI; or (3) remitted MDD with MCI.Results: PACt-MD (Prevention of Alzheimer's dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression) is a trial that randomized 375 older participants with MCI, MDD, or MCI + MDD to cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) or sham-CR + sham-tDCS for 5 days/week for 8 weeks followed by boosters for 5 days/week once every 6 months until participants progress to MCI or ADRD, or the end of the study. Between boosters, participants are asked to train on CR daily. At baseline, end of 8 weeks, and yearly from baseline, participants undergo clinical, cognitive, and functional assessments. The primary aims are to compare the efficacy of CR + tDCS versus sham + sham in preventing: 1) long-term cognitive decline; and 2) incidence of ADRD or MCI. The secondary aim is to assess for cognitive improvement after the 8-week course. We will also explore the moderating and mediating effects of several biomarkers collected from the participants.Conclusion: PACt-MD is unique in combining brain stimulation and a psychosocial intervention to prevent ADRD. PACt-MD is also a platform for studying multi-domain biomarkers that will advance our understanding of the relationships among MCI, MDD, and ADRD. [ABSTRACT FROM AUTHOR]

A diagnosis of mild cognitive impairment is associated with an increase in anxiety and depression and a decrease in psychological well-being. Despite this, individuals with mild cognitive impairment may not receive the appropriate support needed to manage the emotional and practical elements of their diagnosis. A psychosocial group intervention based on the 'Recovery Model' was developed in order to meet these needs. Outcome data from a trial of this group intervention indicated it was successful in meeting its aims. [ABSTRACT FROM AUTHOR]

Objectives: To understand the perceived benefits and drawbacks of a mild cognitive impairment (MCI) diagnosis from the perspective of those living with the label.Methods: Participants were included if they had recently (within 6 months) received a MCI diagnosis. We also recruited close family members to gain their perspectives. Each was interviewed separately with a semi-structured topic guide covering three areas: (1) experience of cognitive impairments and changes in the individual; (2) impact of cognitive impairment(s) on daily activities and social relationships; and (3) experience of the diagnosis process and living with the label. Transcribed interviews were stored in Nvivo® . Grounded theory procedures of memo writing, open coding, constant comparison, and focused coding were used to derive conceptual themes.Results: Eighteen dyads were interviewed. The overarching themes surrounding diagnosis benefits and drawbacks were as follows: (1) emotional impact of the diagnosis; (2) practical benefits and limitations of the diagnosis, in terms of (a) understanding one's symptoms and (b) access to clinical support. Although participants were glad to have clinical support in place, they expressed frustration at the lack of clarity, and the lack of available treatments for MCI. Consequently, living with MCI can be characterized as an ambivalent experience.Conclusion: As a clinical label, MCI appears to have little explanatory power for people living with cognitive difficulties. Work is needed to clarify how clinicians and patients communicate about MCI, and how people can be helped to live well with the label. Despite an emerging body of prognostic studies, people with MCI are likely to continue living with significant uncertainty. Statement of contribution What is already known on this subject? Mild cognitive impairment is a state of cognitive decline between normal cognitive ageing and dementia. This clinical category has been an important domain of academic debate over recent years. From a clinical perspective, diagnosing MCI is a helpful way to enable communication between health professionals, and a diagnosis can be important for patients in need of support and education. However, diagnosis can be fraught with difficulties, while patients have reported significant uncertainty about the label. This study aimed to examine the perceived benefits and drawbacks of receiving a MCI diagnosis. What does this study add? The emotional impact of a MCI diagnosis is complex and raised conflicting and fluctuating emotions in our participants' accounts - most notably worry and relief. Participants were glad to have clinical support available to call on; however, they were frustrated at the lack of 'treatments' available for MCI and were often anxious to slow any cognitive decline down Health psychologists will have an important role to play in understanding and improving clinical communication about MCI. [ABSTRACT FROM AUTHOR]

Aim It is very important to maintain cognitive function in patients with mild cognitive disorder. The aim of the present study was to determine whether the amount of physical activity is associated with memory function in older adults with mild cognitive disorder. Methods A total of 47 older adults with mild cognitive disorder were studied; 30 were diagnosed with mild Alzheimer's disease and 17 with mild cognitive impairment. The global cognitive function, memory function, physical performance and amount of physical activity were measured in these patients. We divided these patients according to their walking speed (<1 m/s or >1 m/s). A total of 26 elderly patients were classified as the slow walking group, whereas 21 were classified as the normal walking group. Results The normal walking group was younger and had significantly better scores than the slow walking group in physical performance. Stepwise multiple linear regression analysis showed that only the daily step counts were associated with the Scenery Picture Memory Test in patients of the slow walking group (β = 0.471, P = 0.031), but not other variables. No variable was significantly associated with the Scenery Picture Memory Test in the normal walking group. Conclusions Memory function was strongly associated with the amount of physical activity in patients with mild cognitive disorder who showed slow walking speed. The results show that lower physical activities could be a risk factor for cognitive decline, and that cognitive function in the elderly whose motor function and cognitive function are declining can be improved by increasing the amount of physical activity. Geriatr Gerontol Int 2014; 14: 758-762. [ABSTRACT FROM AUTHOR]

Aim: Falls are common in patients with cognitive disorder. The purpose of this study was to determine whether global brain atrophy is associated with cognitive function, physical performance and fall incidents in older adults with mild cognitive disorder. Methods: A total of 31 older adults with mild cognitive disorders (mean age 78.9 ± 7.3 years) were studied, and 10 of them had experienced falls and the others had not in the past 1 year. Cognitive function and physical performance were measured in these patients. Global brain atrophy was determined by the Voxel-Based Specific Regional Analysis System for Alzheimer's Disease software. Results: Fallers showed significantly worse scores than the non-fallers in the Global Brain Atrophy Index, Clock Drawing Test (CDT), Verbal Fluency Test (animal), maximum walking time and Timed Up & Go (TUG) Test. The Global Brain Atrophy Index was correlated with the Verbal Fluency Test (animal; r = −0.522), the Verbal Fluency Test with letter (ka; r = −0.337), CDT ( r = −0.547), TUG ( r = 0.276) and Five Chair Stands Test ( r = 0.303) by age-adjusted correlation analyses. Stepwise regression analysis showed that the Global Brain Atrophy Index (β = 1.265, 95% CI 1.022-1.567) was a significant and independent determinant of falls ( R2 = 0.356, P = 0.003). Conclusion: Global brain atrophy might be indicated as one of the risk factors for falls in older adults with mild cognitive disorders. Geriatr Gerontol Int 2013; 13: 437-442. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatitis C has been associated with a decrease in quality of life and with neurological abnormalities. The aim of our study was to investigate the relationship between quality of life and cognitive function.Methods: Quality of life, clinical variables and neuropsychological function were evaluated in 120 patients with hepatitis C (mild chronic hepatitis, compensated cirrhosis and decompensated cirrhosis) and in healthy controls (n=40, in each group).Results: Patients with chronic hepatitis or compensated cirrhosis showed a decrease in quality of life, in spite of unimpaired neuropsychological tests. Patients with decompensated cirrhosis exhibited a further decrease in quality of life and neuropsychological abnormalities. The decrease in quality of life was associated with the severity of liver failure, neuropsychological abnormalities and treatment with beta-blockers or diuretics. However, in the multivariable analysis, only treatment with beta-blockers or diuretics (which was limited to decompensated cirrhosis) was independently associated with quality of life.Conclusions: Hepatitis C causes a decrease in quality of life even in the absence of major cognitive impairment. The mechanisms that worsen quality of life are unknown. However, in cirrhotic outpatients with prior decompensations, treatment with beta-blockers or diuretics appears to have an important effect on quality of life. [Copyright &y& Elsevier]

Background: Little is known about the impact of COVID-19 on mild cognitive disorder., Objective: The aim of this retrospective cohort study was to investigate whether COVID-19 diagnosis is associated with subsequent mild cognitive disorder (MCD) compared to acute upper respiratory infections (AURI)., Methods: This retrospective cohort study used data from the Disease Analyzer database (IQVIA) and included 67,046 patients with first-time symptomatic or asymptomatic COVID-19 diagnoses in 1,172 general practices in Germany between March 2020 and September 2021. Diagnoses were based on ICD-10 codes. Patients diagnosed with AURI were matched to 67,046 patients with COVID-19 using propensity scores based on sex, age, index month, and comorbidities. The index date was the diagnosis date for either COVID-19 or AURI. Associations between the COVID-19 and MCD were studied using conditional Poisson regression models., Results: The incidence of MCD was 7.6 cases per 1,000 person-years in the COVID-19 group and 5.1 cases per 1,000 person-years in the AURI group (IRR = 1.49, 95% CI = 1.22-1.82). The incidence rate ratio decreased strongly with increasing age from 10.08 (95% CI = 4.00-24.42) in the age group≤50 to 1.03 (95% CI = 0.81-1.31) in the age group > 70. In addition, the association between COVID-19 and MCD was significant in women (IRR: 1.70, 95% CI: 1.34-2.16) but not in men (IRR: 1.08, 95% CI: 0.75-1.56)., Conclusion: The incidence of MCD was low but significantly higher in COVID-19 than in AURI patients, especially among younger patients. If a cognitive disorder is suspected, referral to a specialist is recommended., Competing Interests: The authors have no conflict of interest to report., (© 2022 – The authors. Published by IOS Press.)

Objective. The aims were to (i) report the outcome of mild cognitive disorder (MCD) 3.6 years after initial interview and diagnosis; (ii) identify predictors of new cases of MCD. The hypotheses were that (i) persons with MCD are more likely to develop dementia than those without MCD; (ii) symptoms of anxiety or depression predict MCD caseness at follow-up. Design . Longitudinal cohort study. Setting . Community of elderly people (age 70–97 years). Participants . 612 of 897 elderly subjects (mean 76 years) were reinterviewed. Of the 36 MCD cases originally identified, 25 were available at follow-up. 24 incident cases of MCD were identified. Main outcome measures . ICD-10 dementia, DSM-III-R dementia, ICD-10 mild cognitive disorder diagnoses made by the Canberra Interview for the Elderly, tests of anxiety, depression, neuroticism and cognitive performance. Main results .Of the original 25 MCD cases available at follow-up, two had a diagnosis of MCD, and three had a diagnosis of both ICD-10 and DSM-III-R dementia. The prevalence of MCD and DSM-III-R dementia at follow-up was no greater for MCD cases diagnosed at initial interview than in normal subjects at initial interview. There was, however, an increased prevalence of ICD-10 dementia among original MCD cases. At initial interview and at follow-up MCD cases were more anxious and depressed but had similar cognitive performance to normals. For incident cases of MCD the only significant predictor was age. Conclusions . MCD cannot be seen to be a specific forerunner of dementia. Those with a diagnosis of MCD are distinguished more by their anxiety, depression and neuroticism than by their cognitive deficits. © 1997 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Mild cognitive impairment (MCI) is defined as the symptomatic pre-dementia phase on the continuum of cognitive decline. Early recognition and application of potential interventions could prevent or delay the progression to dementia. The Rowland Universal Dementia Assessment Scale (RUDAS) shows good performance in the screening of dementia but has limited data regarding its diagnostic properties in the screening of MCI. The objectives of this study were to assess the psychometric properties of the Thai version of the RUDAS (RUDAS-Thai) in the screening of MCI, identify associated factors for the RUDAS performance, and determine the optimal cutoff point in detecting MCI., Methods: This was a cross-sectional study conducted from January 2020 to March 2021. Older patients at the outpatient clinic of an internal medicine department at a tertiary care hospital in Thailand were examined. Baseline data were collected, and the RUDAS-Thai was administered to each patient. Afterward, a geriatrician assessed each patient for MCI., Results: A total of 150 patients were included, of whom 42 cases (28%) had MCI. The overall performance of the test using an area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval 0.75-0.89). At the optimal cutoff point of 25/30, the AUC was 0.76 with sensitivity and specificity of 76.2 and 75%, respectively. The educational level affected the test performance according to regression analysis. For patients with years of education ≤6 and >6, the optimal cutoff points were 25/30 and 26/30, respectively., Conclusion: The RUDAS-Thai performed well in differentiating patients with MCI from normal cognition; however, it was affected by educational level. A score of 25/30 or lower for persons with ≤6 years of education or 26/30 or lower for persons with higher than 6 years of education is the optimal cutoff point for indication of developing MCI., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

The extent and spatial location of white matter hyperintensities (WMH) on brain MRI may be relevant to the development of cognitive decline in older persons. Here, we introduce a new method, known as the Multi-atlas based Detection and Localization (MADL), to evaluate WMH on fluid-attenuated inversion recovery (FLAIR) data. This method simultaneously parcellates the whole brain into 143 structures and labels hyperintense areas within each WM structure. First, a multi-atlas library was established with FLAIR data of normal elderly brains; and then a multi-atlas fusion algorithm was developed by which voxels with locally abnormal intensities were detected as WMH. At the same time, brain segmentation maps were generated from the multi-atlas fusion process to determine the anatomical location of WMH. Areas identified using the MADL method agreed well with manual delineation, with an interclass correlation of 0.97 and similarity index (SI) between 0.55 and 0.72, depending on the total WMH load. Performance was compared to other state-of-the-art WMH detection methods, such as BIANCA and LST. MADL-based analyses of WMH in an older population revealed a significant association between age and WMH load in deep WM but not subcortical WM. The findings also suggested increased WMH load in selective brain regions in subjects with mild cognitive impairment compared to controls, including the inferior deep WM and occipital subcortical WM. The proposed MADL approach may facilitate location-dependent characterization of WMH in older individuals with memory impairment., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Chronic kidney disease (CKD) affects nearly 9% of global populations and is strongly associated with older age. Neurocognitive disorders (NCDs), which include mild cognitive impairment and dementia, are rising as a result of ageing populations throughout the world. This investigation's aim is to report the frequency of mild to major NCD in a clinical cohort of adults with mild to moderate CKD and diabetes., Setting: Glan Clwyd District general Hospital, North Wales, UK., Participants: We enrolled 178 patients with CKD and diabetes, aged 55 years and over with an estimated glomerular filtration rate <60 >15 mL/min/1.73 m 2 , attending a specialist renal and diabetic outpatient clinic., Outcome Measures: Frequency of mild and major NCD and the association with the stage of CKD was assessed in all patients attending the specialist clinic. The diagnosis of NCD was based on patient and informant interview, case note review, neuropsychological assessment and application of Diagnostic and Statistical Manual of Mental Disorders version 5., Results: This investigation found 86/178 (48%) of the cohort with an NCD ranging from mild (n=49) to major symptoms (n=37). No association was found with NCD and the stage of CKD. Mild and major NCD was associated poorer outcomes in several cognitive domains, including, language, executive, memory, fluency and attention function (p<0.05)., Conclusions: This is the first UK investigation to report that cognitive changes occur in a significant number of older adults with CKD and diabetes. The unexpected finding was that prior to cognitive assessment, not any of the cohort had a pre-existing diagnosis of cognitive impairment, suggesting that the current prevalence and incidence rates of NCD in the general population are possibly significantly underestimated. Our findings also suggest that the cognitive function of patients with CKD should be screened and monitored routinely as part of their overall care management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia., Methods: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline., Results: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53-0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30-17.39, p<0.001)., Conclusion: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.