1.Automatic brain segmentation in cognitive impairment: Validation of AI-based AQUA software in the Southeast Asian BIOCIS cohort.
Ashwati VIPIN ; Rasyiqah BINTE SHAIK MOHAMED SALIM ; Regina Ey KIM ; Minho LEE ; Hye Weon KIM ; ZunHyan RIEU ; Nagaendran KANDIAH
Annals of the Academy of Medicine, Singapore 2025;54(8):467-475
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
2.Analysis of the effectiveness of structured cognitive rehabilitation therapy in post-stroke cognitive impairment patients in Singapore
Yijin LEOW ; Chao DANG ; Nagaendran KANDIAH
Chinese Journal of Nervous and Mental Diseases 2024;50(4):193-208
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.
3.Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia
Kee Hyung PARK ; YoungSoon YANG ; Christopher CHEN ; Yong S. SHIM ; Jacqueline C. DOMINGUEZ ; Chan-Nyoung LEE ; Kyunghun KANG ; Hee-Jin KIM ; Seul-Ki JEONG ; Jee Hyang JEONG ; Zhen HONG ; Soo Jin YOON ; Zhen-Xin ZHANG ; Eun-Joo KIM ; Jae-Won JANG ; Yansheng LI ; Yun XU ; Yu-Te LIN ; Qiumin QU ; Chaur-Jong HU ; Chih-Ho CHOU ; Dongsheng FAN ; Nagaendran KANDIAH ; Yuan-Han YANG ; Chi-ieong LAU ; Leung-Wing CHU ; Huali WANG ; San JUNG ; Seong Hye CHOI ; SangYun KIM
Journal of Clinical Neurology 2021;17(3):376-384
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.
4.Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia
Kee Hyung PARK ; YoungSoon YANG ; Christopher CHEN ; Yong S. SHIM ; Jacqueline C. DOMINGUEZ ; Chan-Nyoung LEE ; Kyunghun KANG ; Hee-Jin KIM ; Seul-Ki JEONG ; Jee Hyang JEONG ; Zhen HONG ; Soo Jin YOON ; Zhen-Xin ZHANG ; Eun-Joo KIM ; Jae-Won JANG ; Yansheng LI ; Yun XU ; Yu-Te LIN ; Qiumin QU ; Chaur-Jong HU ; Chih-Ho CHOU ; Dongsheng FAN ; Nagaendran KANDIAH ; Yuan-Han YANG ; Chi-ieong LAU ; Leung-Wing CHU ; Huali WANG ; San JUNG ; Seong Hye CHOI ; SangYun KIM
Journal of Clinical Neurology 2021;17(3):376-384
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.
5.Clinical Aspects of Neurobehavioral Symptoms of Dementia
YoungSoon YANG ; Nagaendran KANDIAH ; SangYun KIM ; Yong Tae KWAK
Dementia and Neurocognitive Disorders 2020;19(2):54-64
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.
7.Psychometric Properties of Alzheimer's Disease Assessment Scale-Cognitive Subscale for Mild Cognitive Impairment and Mild Alzheimer's Disease Patients in an Asian Context.
Nur Hani ZAINAL ; Eveline SILVA ; Linda Lh LIM ; Nagaendran KANDIAH
Annals of the Academy of Medicine, Singapore 2016;45(7):273-283
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
8.Role of cerebrovascular risk factors in dementia
Shaun Hiu ; Marissa Ong ; Nagaendran Kandiah
Neurology Asia 2016;21(2):103-111
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
10.Effectiveness of Montreal Cognitive Assessment for the diagnosis of mild cognitive impairment and mild Alzheimer's disease in Singapore.
Amanda NG ; Ivane CHEW ; Kaavya NARASIMHALU ; Nagaendran KANDIAH
Singapore medical journal 2013;54(11):616-619
INTRODUCTIONMild cognitive impairment (MCI) is an important clinical entity with significant management implications. However, traditional screening tools lack the sensitivity needed to detect amnestic MCI (MCI-A). Montreal Cognitive Assessment (MoCA) has yet to be validated for the diagnosis of MCI in a multiracial society such as Singapore. We thus aimed to study the effectiveness of MoCA for the diagnosis of MCI-A in the Singapore population.
METHODSData on patients with MCI-A and mild Alzheimer's disease (AD) was obtained from a prospectively collected clinical database between January 2008 and January 2011. Patients with no cognitive impairment (NCI) were recruited from among the spouses and friends of patients attending the memory clinic.
RESULTSThere were a total of 212 participants (103 NCI, 49 MCI-A, 60 mild AD). For the diagnosis of MCI-A, a MoCA score of < 26 for patients with ≤ 10 years of education, and a score of < 27 for patients with > 10 years of education provided a sensitivity of > 94%. For the diagnosis of mild AD, a MoCA score of < 24 for patients with ≤ 10 years of education, and a score of < 25 for patients with > 10 years of education provided a sensitivity of > 85%.
CONCLUSIONIn the Singapore population, we recommend cutoff scores of 26/27 and 24/25 be used to detect MCI-A and mild AD, respectively, when using MoCA. For patients with ≤ 10 years of education, a +1 point correction is needed.
Aged ; Aged, 80 and over ; Alzheimer Disease ; diagnosis ; therapy ; Cognitive Dysfunction ; diagnosis ; therapy ; Cohort Studies ; Databases, Factual ; Developing Countries ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Neuropsychological Tests ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Severity of Illness Index ; Singapore

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