INTRODUCTION: Interpretation and analysis of magnetic resonance imaging (MRI) scans in clinical settings comprise time-consuming visual ratings and complex neuroimage processing that require trained professionals. To combat these challenges, artificial intelligence (AI) techniques can aid clinicians in interpreting brain MRI for accurate diagnosis of neurodegenerative diseases but they require extensive validation. Thus, the aim of this study was to validate the use of AI-based AQUA (Neurophet Inc., Seoul, Republic of Korea) segmentation software in a Southeast Asian community-based cohort with normal cognition, mild cognitive impairment (MCI) and dementia. METHOD: Study participants belonged to the community-based Biomarker and Cognition Study in Singapore. Participants aged between 30 and 95 years, having cognitive concerns, with no diagnosis of major psychiatric, neurological or systemic disorders who were recruited consecutively between April 2022 and July 2023 were included. Participants underwent neuropsychological assessments and structural MRI, and were classified as cognitively normal, with MCI or with dementia. MRI pre-processing using automated pipelines, along with human-based visual ratings, were compared against AI-based automated AQUA output. Default mode network grey matter (GM) volumes were compared between cognitively normal, MCI and dementia groups. RESULTS: A total of 90 participants (mean age at visit was 63.32±10.96 years) were included in the study (30 cognitively normal, 40 MCI and 20 dementia). Non-parametric Spearman correlation analysis indicated that AQUA-based and human-based visual ratings were correlated with total (ρ=0.66; P<0.0001), periventricular (ρ=0.50; P<0.0001) and deep (ρ=0.57; P<0.0001) white matter hyperintensities (WMH). Additionally, volumetric WMH obtained from AQUA and automated pipelines was also strongly correlated (ρ=0.84; P<0.0001) and these correlations remained after controlling for age at visit, sex and diagnosis. Linear regression analyses illustrated significantly different AQUA-derived default mode network GM volumes between cognitively normal, MCI and dementia groups. Dementia participants had significant atrophy in the posterior cingulate cortex compared to cognitively normal participants (P=0.021; 95% confidence interval [CI] -1.25 to -0.08) and in the hippocampus compared to cognitively normal (P=0.0049; 95% CI -1.05 to -0.16) and MCI participants (P=0.0036; 95% CI -1.02 to -0.17). CONCLUSION Our findings demonstrate high concordance between human-based visual ratings and AQUA-based ratings of WMH. Additionally, the AQUA GM segmentation pipeline showed good differentiation in key regions between cognitively normal, MCI and dementia participants. Based on these findings, the automated AQUA software could aid clinicians in examining MRI scans of patients with cognitive impairment.
Humans ; Cognitive Dysfunction/pathology* ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Female ; Aged ; Artificial Intelligence ; Software ; Dementia/diagnostic imaging* ; Aged, 80 and over ; Adult ; Singapore ; Neuropsychological Tests ; Brain/pathology* ; Cohort Studies ; Gray Matter/pathology* ; Southeast Asian People

Objective Literature on cognitive prognoses in association with stroke-related and pre-stroke factors,are surprisingly meagre.Prognoses of patients with post stroke cognitive impairment(PSCI)to structured cognitive rehabilitation are not clearly understood.This study aimed to compare if the prognoses of stroke survicors after cognitive rehabilitation programme was associated with chronic cerebrovascular disease(CVD).Methods An eight-week non-pharmacological clinical programme was ran for patients with mild strokes to provide clinical support to stroke patients and collect longitudinal data on stroke prognoses.149 ischemic stroke survivors(age 63.6±9.66,64.4%males)underwent an eight-week structured group cognitive rehabilitation programme.Baseline,immediate post programme(Immediate-PP)and 6-month post programme(6-month-PP)global cognitive and quality of life outcomes were assessed by Montreal cognitive assessment(MoCA)and dementia-quality of life instrument(DemQOL).Regression analyses evaluated the influence of cognitive rehabilitation on outcomes.Results With every past stroke experienced by patients,they were less likely to demonstrate an improvement in MoCA score Immediate-PP(OR=2.17,95%CI:0.980-4.813,P=0.056).Patients with severe white matter hyperintensities were less likely to demonstrate an improvement in MoCA scores Immediate-PP compared to Baseline(OR=2.13,95%CI:1.04-4.38,P=0.039).Finally,patients with microhemorrhages in the deep region were less likely to demonstrate an improvement in MoCA at 6-month-PP(OR=19.93,95%CI:1.04-384,P=0.047).Conclusions Pre-stroke CVD is associated with poorer cognitive outcomes post cognitive rehabilitation.Our initial programme shows promising results-however further research into cognitive rehabilitation for stroke survivors with pre-stroke CVD is needed.The findings from our clinical rehabilitation programme will be useful guiding the design of a clinical trial.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Neurobehavioral symptoms of dementia (NBSD) are very common and are significant symptoms of the illness, contributing most to caregiver burdens and often resulting in premature institutionalization of the person with dementia. The main symptoms of NBSD are anxiety, depression, delusions, and hallucinations. NBSD produce significant problems for both patients and caregivers. The pathophysiology of NBSD is determined by genetic, structural, or environmental factors. Therefore, treatment of NBSD requires continuous and organic cooperation between patients, caregivers, social environments, and doctors. Therefore, it is important for neurologists, who mainly view NBSD for dementia patients, to increase their understanding of these more comprehensive areas as well as the latest insights and treatments to help patients and caregivers.

INTRODUCTIONThe purpose of the current study is to assess the psychometric properties of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) on patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) in a multicultural Asian context.

MATERIALS AND METHODSSixty-four mild AD patients (mean age ± SD; 72.24 ± 7.88 years), 80 MCI patients (66.44 ± 7.45 years) and 125 healthy controls (HCs) (61.81 ± 6.96 years) participated in the study. Participants underwent a clinical interview and serial neuropsychological testing. ADAS-Cog total and subtest scores were compared across the 3 groups. Receiver operating characteristics (ROC) analysis were performed and sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated.

RESULTSPatients with MCI attained significantly worse neuropsychological test scores than healthy controls but significantly better results than patients with mild AD on ADAS-Cog total score, subtest items, and the delayed recall item (P <0.001). The best cutoff score to differentiate between MCI and HC was ≥4 (sensitivity = 0.73, specificity = 0.69, PPV = 0.90, NPV = 0.40), while the best cutoff score to distinguish between MCI and mild AD was ≥12 (sensitivity = 0.86, specificity = 0.89, PPV = 0.99, NPV = 0.32). Evidence of internal consistency of the ADAS-Cog (Cronbach α = 0.85) as well as convergent validity with the Mini-Mental State Examination (MMSE) (ρ = -0.75) and Montreal Cognitive Assessment (MoCA) (ρ = -0.81) (both P <0.001) was also found.

CONCLUSIONThe ADAS-Cog which is widely used in clinical trials is applicable to the Asian cohort. It is useful in the detection of MCI and mild AD as well as in distinguishing these 2 conditions.

Aged ; Aged, 80 and over ; Alzheimer Disease ; diagnosis ; psychology ; Case-Control Studies ; Cognitive Dysfunction ; diagnosis ; Female ; Humans ; Male ; Mental Status Schedule ; Middle Aged ; Neuropsychological Tests ; Predictive Value of Tests ; Psychiatric Status Rating Scales ; Psychometrics ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Singapore

With the rapid increase in the prevalence of dementia worldwide there has been significant research into modifiable risk factors for dementia. In this regard cerebrovascular diseases (CVD) represent a potential therapeutic target in the fight against the epidemic of dementia. Both large vessel CVD and small vessel disease in the form of chronic lacunes, white matter hyperintensity, microbleeds, and perivascular spaces have been strongly associated with the risk of developing dementia. These CVD factors may initiate or accelerate the amyloid and tau cascades resulting in greater rates of neurodegeneration and dementia. Understanding the precise mechanisms for the interaction between CVD and neurodegeneration will allow development of potential interventional targets. These CVD risk factors may be of particular relevance to the Asian population where a high burden of small vessel CVD has been demonstrated in Asian patients with dementia
Dementia ; Cerebrovascular Disorders

Cognition Disorders ; diagnosis ; Decision Making ; Humans ; Mental Competency ; legislation & jurisprudence ; Physicians ; Singapore

Dementia is a syndrome characterised by cognitive, behavioural and neurological deficits. Both neurodegenerative and non-neurodegenerative conditions can result in dementia. Neurodegenerative diseases include diseases such as Alzheimer’s disease, Frontotemporal Dementia and Dementia with Lewy body, while nonneurodegenerative conditions include conditions such as vascular dementia and normal pressure hydrocephalus. The prevalence of dementia is on a rising trend with the rapidly ageing population in Singapore. Early diagnosis of dementia is important to allow timely pharmacological and non-pharmacological interventions. A thorough history, cognitive evaluation along with suitable investigational studies is necessary for early diagnosis. The ability to diagnose dementia at the earliest stages has been greatly improved with the use of biomarkers such as medial temporal atrophy on MR imaging and cerebrospinal fluid beta amyloid levels. A 4-step approach to dementia evaluation, incorporating local data, where possible can be used: The first step requires the exclusion of delirium as the cause of the forgetfulness or confusion; the second step involves establishing the diagnosis of dementia; the third step assesses for the behavioural, functional and social problems associated with dementia; and the final step, with the use of a focused history, physical examination, investigations and selected use of neuroimaging, attempts to establish the aetiological diagnosis of the dementia. The management of dementia requires a multidisciplinary approach. While acetyl cholinesterase inhibitors and NMDA antagonist can slow cognitive deterioration, research for newer disease modifying drugs which target the underlying pathology is ongoing. Research into nonpharmacological interventions such as cognitive training is also on-going.