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Background: Behavioral and psychological symptoms are one of the earliest observable changes when a person experiences cognitive decline. These symptoms are common and are known as Neuropsychiatric symptoms(NPS), which increases risk of progression to dementia. The prevalence of NPS was compared in a cohort of Southeast Asian adults with Subjective Cognitive Decline(SCD) and Mild Cognitive Impairment(MCI). Method: This study utilized cross‐sectional data from the Biomarkers and Cognition Study, Singapore(BIOCIS). From February to December 2022, participants who met criteria for SCD and MCI in accordance with NIA‐AA's criteria were classified into two groups, NPS and without‐NPS, based on clinical cut‐offs of Depression Anxiety Stress Scales(DASS) scores. Self‐reported questionnaires assessed behavioral symptoms ‐ Mild Behavioral Impairment‐Checklist(MBI‐C); Dementia‐Quality of Life Instrument(Dem‐QOL); International Physical Activity Questionnaire(IPAQ); and Pittsburgh Sleep Quality Index(PSQI). Group comparisons of data were applied separately using univariate analyses. A Receiver Operating Characteristic analysis was conducted to test the diagnostic performance of MBI‐C total, MBI‐C‐subdomains, and PSQI in distinguishing participants with NPS and without‐NPS. Result: 488 participants (μ age = 62.7±9.64,42.2% males) were analyzed. 133(27.25%) reported significant NPS symptoms. Participants with NPS reported significantly more symptoms on MBI‐C‐total(p<.001); interest(p<.001); mood(p<.001); control(p<.001), social(p<.001), and beliefs(p<.001) subdomains; poorer sleep(p<.001) and lower quality of life(p<.001) compared to participants without‐NPS(Table 1). MBI‐C‐total, MBI‐C‐mood and MBI‐C‐control subdomains were effective in discriminating between participants with and without NPS, with an acceptable Area Under the Curve:.782(.732‐.833) for MBI‐C‐total,.753(.699‐.807) for MBI‐C‐mood, and.753(.699‐.807) for MBI‐C‐control(Figure 1 and Table 2). Conclusion: In a prodromal cohort of southeast Asians, participants with NPS reported significantly worse scores on MBI‐C‐total and subdomains, specifically ‐ decreased motivation, emotional dysregulation, impulse control, social inappropriateness, abnormal perceptions, as well as poorer sleep quality and a lower quality of life compared to participants without‐NPS. The results are keeping with the strong evidence that behavioral changes are among the first symptoms noticeable to the person themselves as they begin to experience cognitive decline. The self‐reported questionnaires used are easily administered and brief, which has important real‐world relevance for early diagnoses of, and timely intervention for prodromal dementia. Further studies of BIOCIS is on‐going to investigate the impact of NPS on cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Cognitive tests play a crucial role in evaluating mild cognitive impairment (MCI) and dementia. As most tests are originally developed in English‐speaking cohorts, their application in multilingual populations will need to be translated and may affect the test psychometrics. Therefore, the VCAT was developed as a language‐neutral visual‐based assessment to mitigate this issue. Although the VCAT has been validated in Southeast Asian countries, its performance in wider language cohorts remains unclear. Here, we aim to compare the utility of VCAT with established screening tests, Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE), in distinguishing MCI and dementia from cognitively normal (CN) individuals in a multinational study. Method: This collaboration between Canada, China, India, Korea and Singapore recruited 614 participants (306 CN, 212 MCI, 94 Dementia). The administration of the cognitive tests were standardized across all study sites. Participants underwent the MMSE, MoCA, and VCAT on the same day, with their scores and demographic data (age, gender, years of education, ethnicity, primary written and spoken language) collected in the centers respectively. The performance of VCAT in distinguishing MCI and dementia from CN were assessed within each sites using the area under the curve (AUC). Result: Baseline demographics of the participants in each site were summarized in Table 1. The mean (SD) MMSE, MoCA and VCAT scores in each diagnostic group across all countries were summarized in Table 2. The mean (SD) VCAT scores across all countries for CN, MCI and dementia were 25.91 (3.14); 21.00 (5.36) and 11.91 (4.79) respectively. Corresponding scores for MoCA were 26.09 (2.76); 22.62 (4.43); 14.02 (5.17) and corresponding scores for MMSE were 28.34 (1.79); 26.55 (2.90); 18.91 (4.81). The AUC of VCAT in detecting cognitive impairment (MCI+Dementia) was found to be 0.83 (95%CI 0.80 to 0.86), which is comparable to the MoCA 0.82 (95%CI 0.78 to 0.85) and the MMSE 0.78 (95%CI 0.74 to 0.81). Conclusion: VCAT was comparable to the MoCA and MMSE in distinguishing cognitive impairment from CN in a multinational, multilingual population. Further studies with wider language populations are needed to further validate the utility of VCAT globally. [ABSTRACT FROM AUTHOR]

Background: Post Stroke Cognitive Impairment (PSCI) is seen in 40‐60% of patients with ischemic strokes. Response of patients with PSCI to structured cognitive rehabilitation is not clearly understood. We evaluated baseline variables that predict response to an eight‐week non‐pharmacological intervention among patients with mild strokes and compared the responses to non‐pharmacological intervention among acute stroke patients with and without chronic cerebrovascular disease (CVD). Method: 139 ischemic stroke survivors were recruited from a tertiary hospital in Singapore. All patients underwent an eight‐week structured group cognitive rehabilitation programme (Figure 1). Baseline, immediate post‐intervention (Immediate‐PI) and 6‐month post intervention (6‐month‐PI) global cognitive and quality of life (QOL) outcomes were assessed by Montreal Cognitive Assessment (MoCA) and Dementia‐Quality of Life (DemQOL). Regression analyses evaluated the influence of cognitive rehabilitation on outcomes. Result: The mean age of subjects were 63.6 (±9.66) with 64.4% males. Baseline MoCA and DemQOL scores were 23.30 (±3.05) and 79.16 (±14.80). At Immediate‐PI, patients with more past strokes (p = 0.033) and severe white matter hyperintensities (WMH) (p = 0.048), benefited less on global cognitive outcome (Table 1). Male patients (p = 0.074) and patients with more severe WMH (p = 0.048) benefited less on QOL outcome (Table 2). At 6‐month‐PI, patients with microhemorrhages in the deep region (p = 0.002) were less likely to sustain cognitive improvement. With every past stroke experienced, patients were less likely to experience an improvement in MoCA score Immediate‐PI (OR = 2.17, 95% CI: 0.980‐4.813, p = 0.056). with severe WMH were less likely to experience an improvement in MoCA scores Immediate‐PI 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 retain the improvements in MoCA at 6‐month‐PI (OR = 19.93, 95% CI: 1.04‐384, p = 0.047) Conclusion: Pre‐stroke CVD were associated with worse cognitive and QoL outcomes post cognitive rehabilitation. Understanding factors that result in poor response to rehabilitation will allow clinicians to better select stroke survivors for cognitive rehabilitation. Future research could build on these findings and allocate more resources to these at‐risk groups for post‐stroke care, therefore reducing the global burden of stroke and ensuring a better QOL for stroke survivors. [ABSTRACT FROM AUTHOR]

Background: The APOE‐ε4 (APOE4) allele and cerebrovascular disease (CVD), represented by surrogate MRI measures involving white matter hyperintensities (WMH) are key dementia risk factors [Tosto et al.,2015; Mahley et al.,2006]. They relate to grey matter volume (GMV) and cognitive decline, and demonstrate increased occurrence with lowered age of dementia onset [Boyle et al.,2016; Brickman et al.,2014]. Whether APOE4 is a key effect modifier in the relationship between WMH and GMV needs further exploration. Therefore, we examined independent and interactive effects of WMH and APOE4 on GMV and cognition in cognitively unimpaired (CU) and early‐stage dementia (ESD) participants. We hypothesized that participants with higher WMH load would demonstrate worse GMV atrophy and greater cognitive impairment, especially among APOE4 carriers. Method: We studied 259 CU and 192 ESD (mild cognitive impairment, mild dementia) from a Singapore research cohort with neuroimaging, APOE genotyping and neuropsychological assessment data (Table 1). We investigated independent and interactive effects of WMH and APOE4 on whole‐brain voxel‐wise GMV using voxel‐based morphometry (uncorrected p<0.001; minimum cluster size=100 voxels). Multiple linear regression models assessed APOE4 and WMH interactive effects on global cognition (mini‐mental state examination–MMSE), memory (Alzheimer's disease assessment scale‐delayed word recall) and executive function (Color Trails 2) in ESD. Result: Higher WMH load associated with widespread voxel‐wise grey matter atrophy across frontal, parietal, temporal and occipital lobes in CU and ESD (Fig.1). When stratified by APOE4 status, APOE4 carriers showed regions of GM atrophy in frontal, temporal and parietal regions. When examining the interaction between WMH and APOE4 on GMV, contrary to our hypothesis, APOE4 non‐carriers showed more extensive derogatory effects of WMH on GMV than APOE4 carriers (Fig.2). These effects extended into ESD cognitive performance with APOE4 non‐carriers displaying deteriorating global and executive function with increasing WMH load than APOE4 carriers (Fig.3). Conclusion: We illustrate APOE4 status as likely a key moderator in the relationship between WMH and GMV in both preclinical CU and ESD stages. With differential effects of WMH on GMV and cognition between APOE4 carriers and non‐carriers, interventions targeting WMH may need a differential approach depending on the APOE4 status. [ABSTRACT FROM AUTHOR]

Background: The amyloid‐tau‐neurodegeneration (ATN) scheme enables unbiased biomarker‐based diagnoses, independent of cognitive status and temporal ordering of AD pathogenic mechanisms [Jack et al.,2016]. ATN profiles in the diverse Southeast‐Asian region will provide important insights into the ATN framework and its association with cognition [Hilal et al.,2017; Knopman et al., 2018]. We examined the effect of amyloid‐beta status on longitudinal cognitive trajectory in young and late‐onset patients as well as impact of ATN categories on longitudinal cognition in a Southeast‐Asian cohort. We hypothesized that age of onset would differentially influence the association between amyloid status and longitudinal cognition. Method: We studied 92 patients with cognitive impairment from the Singapore YouNg Dementia Cohort. Patients underwent structural‐MRI and lumbar puncture for cerebrospinal fluid amyloid‐beta (1–42), phosphorylated‐tau (p‐tau) and total‐tau (t‐tau) to assess biomarker positivity [Blennow et al., 2020]. A cut‐off age of 60 years was used to define young‐onset cognitive impairment. Separately, ATN profiles were assigned based on cerebrospinal fluid biomarker levels: normal biomarker profile (A‐T‐N‐), suspected non‐Alzheimer's pathology (SNAP: A‐T±N±) and Alzheimer's continuum (A+T±N±). Linear mixed effects models assessed longitudinal group differences in mini‐mental state examination (MMSE) trajectory. Result: Young (<60yrs) sporadic amyloid‐positive, patients demonstrated significantly greater decline in longitudinal MMSE scores (AmyloidStatus*AgeOfOnset*Time: β=2.82, p=0.0193; Fig. 1) compared to older (≥60yrs) amyloid‐positive counterparts. Across the three ATN categories, there were no differences in baseline age, sex, white matter hyperintensities, medial temporal atrophy or APOE4 status (Table 1). Patients along the Alzheimer's continuum showed a greater decline in MMSE scores over time compared to both normal biomarker A‐T‐N‐ (β=−2.23, p=0.001; Fig. 2‐3) and SNAP patients (β=−2.05, p=0.004; Fig. 2‐3). MMSE decline did not differ between SNAP and A‐T‐N‐ groups. Conclusion: We show steeper MMSE decline in young amyloid‐positive patients than their amyloid‐positive older counterparts. Additionally, Alzheimer's continuum patients showed steeper MMSE decline than A‐T‐N‐ and SNAP patients. These findings provide insights into mechanisms for the more aggressive cognitive decline frequently observed in younger patients. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain intervention to improve cognitive performance. Therefore, we aim to investigate the utility of a novel, scalable multi‐domain digital intervention as a therapeutic solution to prevent or reverse cognitive decline. Method: 30 amnestic MCI patients were enrolled in a pilot open‐label clinical trial of a 10‐week digital therapeutic intervention using NG‐001 delivered via a tablet. 27 participants completed the trial and their data were analyzed. NG‐001 consisted of weekly 1‐hour trainings spread across several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. The outcome composite scores were calculated from the Neuropsychological Test Battery including Overall Cognition, Processing Speed, Executive Functioning, Overall Memory as well as Immediate and Delayed Memory. Composites were calculated into Z‐scores based on normative data from age and education‐adjusted reference groups. Changes in the Z‐scores were then assessed using paired Wilcoxon signed ranked tests (two‐tailed) and the effect size was calculated using Hedges' g. Result: Compared to baseline, at post‐intervention, MCI patients showed significant improvements in Overall Cognition (‐0.440 to ‐0.213, g = 0.352), Overall Memory (‐0.587 to ‐0.132, g = 0.407), Immediate Memory (‐0.549 to ‐0.030, g = 0.512) and Delayed Memory (‐0.626 to ‐0.233, g = 0.305). There were no significant changes in Processing Speed or in Executive Functioning (ps >.05). Conclusion: NG‐001 significantly improved memory (both immediate and delayed) for amnestic MCI patients, indicating its potential as a form of digital therapeutics for early intervention of memory impairment in MCI. Further research is needed to investigate the mechanisms involved in this improvement, and whether modifications can be made to extend its facilitatory effect to other cognitive domains such as executive functioning and language. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a digital intervention that is accessible and scalable so that the benefits of improving behavioral outcomes can be attained on a larger scale. Here, we studied the effectiveness of a novel multi‐domain digital cognitive intervention on NPS among patients with mild cognitive impairment (MCI). Method: We conducted a pilot 10‐week open‐label clinical trial of 30 MCI patients using the NG‐001, a multi‐domain digital intervention. NG‐001 is a digital program which consists of weekly 1‐hour training in several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. Participants completed the Depression Anxiety Stress Scale (DASS) and the Mild‐Behavioral Impairment‐Checklist (MBI‐C) at baseline and at the end of the trial. Changes in DASS and MBI‐C scores were assessed using paired Wilcoxon signed ranked tests (two‐tailed) and effect sizes were reported using Hedges' g. Result: MCI patients showed significant improvements in depression (4.643 vs. 3.214, g = 0.228), anxiety (6.357 vs. 3.786, g = 0.440) and stress (7.786 vs. 5.429, g = 0.356) scores as measured by DASS with NG‐001 intervention (Figure 1). MCI patients also showed significant improvements in MBI‐C total scores (3.29 vs. 1.43, g = 0.47), the apathy sub‐domain scores (0.96 vs. 0.21, g = 0.54), and the affect sub‐domain scores (1.25 vs. 0.43, g = 0.47) with NG‐001 intervention (Figure 2). Importantly, there was high compliance among the participants who completed the full 10‐week intervention. Conclusion: A 10‐week multi‐domain digital intervention with NG‐001 reduces the severity of NPS among MCI patients. A longer trial with a control arm is needed to further determine the efficacy of NG‐001 for NPS among MCI patients. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain intervention to improve cognitive performance. Therefore, we aim to investigate the utility of a novel, scalable multi‐domain digital intervention as a therapeutic solution to prevent or reverse cognitive decline. Method: 30 amnestic MCI patients were enrolled in a pilot open‐label clinical trial of a 10‐week digital therapeutic intervention using NG‐001 delivered via a tablet. 27 participants completed the trial and their data were analyzed. NG‐001 consisted of weekly 1‐hour trainings spread across several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. The outcome composite scores were calculated from the Neuropsychological Test Battery including Overall Cognition, Processing Speed, Executive Functioning, Overall Memory as well as Immediate and Delayed Memory. Composites were calculated into Z‐scores based on normative data from age and education‐adjusted reference groups. Changes in the Z‐scores were then assessed using paired Wilcoxon signed ranked tests (two‐tailed) and the effect size was calculated using Hedges' g. Result: Compared to baseline, at post‐intervention, MCI patients showed significant improvements in Overall Cognition (‐0.440 to ‐0.213, g = 0.352), Overall Memory (‐0.587 to ‐0.132, g = 0.407), Immediate Memory (‐0.549 to ‐0.030, g = 0.512) and Delayed Memory (‐0.626 to ‐0.233, g = 0.305). There were no significant changes in Processing Speed or in Executive Functioning (ps >.05). Conclusion: NG‐001 significantly improved memory (both immediate and delayed) for amnestic MCI patients, indicating its potential as a form of digital therapeutics for early intervention of memory impairment in MCI. Further research is needed to investigate the mechanisms involved in this improvement, and whether modifications can be made to extend its facilitatory effect to other cognitive domains such as executive functioning and language. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a digital intervention that is accessible and scalable so that the benefits of improving behavioral outcomes can be attained on a larger scale. Here, we studied the effectiveness of a novel multi‐domain digital cognitive intervention on NPS among patients with mild cognitive impairment (MCI). Method: We conducted a pilot 10‐week open‐label clinical trial of 30 MCI patients using the NG‐001, a multi‐domain digital intervention. NG‐001 is a digital program which consists of weekly 1‐hour training in several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. Participants completed the Depression Anxiety Stress Scale (DASS) and the Mild‐Behavioral Impairment‐Checklist (MBI‐C) at baseline and at the end of the trial. Changes in DASS and MBI‐C scores were assessed using paired Wilcoxon signed ranked tests (two‐tailed) and effect sizes were reported using Hedges' g. Result: MCI patients showed significant improvements in depression (4.643 vs. 3.214, g = 0.228), anxiety (6.357 vs. 3.786, g = 0.440) and stress (7.786 vs. 5.429, g = 0.356) scores as measured by DASS with NG‐001 intervention (Figure 1). MCI patients also showed significant improvements in MBI‐C total scores (3.29 vs. 1.43, g = 0.47), the apathy sub‐domain scores (0.96 vs. 0.21, g = 0.54), and the affect sub‐domain scores (1.25 vs. 0.43, g = 0.47) with NG‐001 intervention (Figure 2). Importantly, there was high compliance among the participants who completed the full 10‐week intervention. Conclusion: A 10‐week multi‐domain digital intervention with NG‐001 reduces the severity of NPS among MCI patients. A longer trial with a control arm is needed to further determine the efficacy of NG‐001 for NPS among MCI patients. [ABSTRACT FROM AUTHOR]

Background: Posterior Cortical Atrophy (PCA) has been widely studied internationally, but there is limited data on its clinical and biomarker characteristics among Southeast Asians. We aim to describe a case series of PCA patients in this part of the world and explore how the new PCA consensus classification (Crutch et al., 2017) could be applied in this cohort. Method: A retrospective review of the Singapore Young Onset Dementia (YOD) research database from a tertiary neurology center was performed. Available demographic, clinical and biomarker data of patients with a clinical diagnosis of PCA were extracted. Result: Of 290 patients with YOD, ten patients (5 males; 5 females) with a clinical diagnosis of PCA were identified. Mean (SD) age of onset was 54.70 (4.11), duration between symptom onset and neurological consultation was 3.90 (1.45) years. All patients reported insidious onset and gradual progression of symptoms. Upon neurological examination, principle types of cognitive deficits seen were acalculia (80%), finger agnosia (70%), simultagnosia (60.0%) and agraphia (50%). In another sub‐group with available MRI scans (n=7), all showed biparietal cortical atrophy, five (71.0%) had concomitant bilateral medial temporal lobe atrophy and white matter hyperintensities of varying severity was noted in four (57.0%) patients. Among patients with known APOE genotyping (n=8), there was one e2e3 six e3e3 and one e4e4. Findings on cerebrospinal Ab‐42 and tau levels was available (n=7), mean (SD) of Ab‐42, phosphor‐tau and total tau levels were 525.1 (195.5)pg/ml, 72.1 (22.9)pg/ml and 611.3 (246.9)pg/ml respectively. Based on the new consensus classification for PCA (Crutch et al., 2017) and incorporating the CSF Ab‐42 criterion cut‐off for AD by Dubois et al. (2014), our series consists of one PCA‐AD (10.0%) and nine PCA‐pure (90.0%) However, if the CSF tau/ Ab‐42 ratio >0.52 (Duits et al., 2014) for biomarker diagnosis of AD is used, there would be seven PCA‐AD (70%) and three PCA‐plus (30%). Conclusion: PCA patients tend to present late in clinic and greater awareness on the presentation of PCA is needed for earlier diagnosis and timely intervention. Also, the sensitivity of the different CSF criteria for AD in diagnosing PCA‐AD would require further analyses in larger cohorts. [ABSTRACT FROM AUTHOR]

Background: Posterior Cortical Atrophy (PCA) has been widely studied internationally, but there is limited data on its clinical and biomarker characteristics among Southeast Asians. We aim to describe a case series of PCA patients in this part of the world and explore how the new PCA consensus classification (Crutch et al., 2017) could be applied in this cohort. Method: A retrospective review of the Singapore Young Onset Dementia (YOD) research database from a tertiary neurology center was performed. Available demographic, clinical and biomarker data of patients with a clinical diagnosis of PCA were extracted. Result: Of 290 patients with YOD, ten patients (5 males; 5 females) with a clinical diagnosis of PCA were identified. Mean (SD) age of onset was 54.70 (4.11), duration between symptom onset and neurological consultation was 3.90 (1.45) years. All patients reported insidious onset and gradual progression of symptoms. Upon neurological examination, principle types of cognitive deficits seen were acalculia (80%), finger agnosia (70%), simultagnosia (60.0%) and agraphia (50%). In another sub‐group with available MRI scans (n=7), all showed biparietal cortical atrophy, five (71.0%) had concomitant bilateral medial temporal lobe atrophy and white matter hyperintensities of varying severity was noted in four (57.0%) patients. Among patients with known APOE genotyping (n=8), there was one e2e3 six e3e3 and one e4e4. Findings on cerebrospinal Ab‐42 and tau levels was available (n=7), mean (SD) of Ab‐42, phosphor‐tau and total tau levels were 525.1 (195.5)pg/ml, 72.1 (22.9)pg/ml and 611.3 (246.9)pg/ml respectively. Based on the new consensus classification for PCA (Crutch et al., 2017) and incorporating the CSF Ab‐42 criterion cut‐off for AD by Dubois et al. (2014), our series consists of one PCA‐AD (10.0%) and nine PCA‐pure (90.0%) However, if the CSF tau/ Ab‐42 ratio >0.52 (Duits et al., 2014) for biomarker diagnosis of AD is used, there would be seven PCA‐AD (70%) and three PCA‐plus (30%). Conclusion: PCA patients tend to present late in clinic and greater awareness on the presentation of PCA is needed for earlier diagnosis and timely intervention. Also, the sensitivity of the different CSF criteria for AD in diagnosing PCA‐AD would require further analyses in larger cohorts. [ABSTRACT FROM AUTHOR]

Background: Hypertension and white matter hyperintensity(WMH) burden are major risk‐factors for Alzheimer's disease[Pantoni et al.,2010;Sweeney et al.,2018]. Prior studies show variable grey matter alterations, involving both negative and positive associations, independently related to WMH and hypertension in early stages of late‐onset AD[Vipin et al.,2018;Foster‐Dingley et al.,2015;Tuladhar et al.,2015;Den Heijer et al.,2003]. However, the effect of incremental WMH load and concomitant hypertension on brain structure in young‐onset mild cognitive impairment(MCI) remains to be elucidated. Such investigations may provide better insight into relationships between WMH, hypertension and dementia risk. We thus examine the influence of increasing WMH load on grey matter volume(GMV) as well as on the association between blood pressure(BP) and GMV in young‐onset MCI. We hypothesize that WMH burden and BP will have derogatory effects on GMV, especially under high WMH conditions. Method: T1‐MRI data from 78 MCI subjects(<65years) from the Singapore‐YouNg‐Dementia‐Cohort was studied. WMH load was divided into low(0.00‐1.49ml), medium(1.50‐4.99ml) and high(>5.00ml). Voxel‐based morphometry(VBM) assessed whole‐brain voxel‐wise changes related to increasing WMH load between hypertensive(systolic‐BP>130mmHg)[Whelton et al.,2017] and non‐hypertensive subjects. Pearson's correlation analysis tested associations between GMV from key Executive‐Control‐Network(ECN) and Default‐Mode‐Network(DMN) regions‐of‐interest(ROI)[Shirer et al.,2012] and vascular risk‐factors. Result: Whole‐brain VBM revealed less GMV reduction in hypertensive compared to non‐hypertensive subjects in frontal and temporal regions at low‐WMH load, with more pronounced effects at medium‐WMH load (Fig.1;uncorrected‐p<0.001, cluster‐size‐threshold:p<0.05). However, at high‐WMH load, hypertensive and non‐hypertensive subjects showed no differences in GMV. Additionally, at low‐WMH load, average and ROI‐specific DMN(bilateral posterior‐cingulate‐cortex, precuneus;p<0.05) and ECN(left[p<0.05] and right[p<0.10] posterior‐parietal‐cortex) GMV related positively to WMH but showed no association at medium‐WMH load. Importantly, only high‐WMH load was associated with lower ECN(p<0.05) and DMN(p<0.10) GMV(Fig.2). These associations remained regardless of hypertension status. Additionally, high systolic‐BP related to lower GMV at high‐WMH load only(Fig.3). Conclusion: Our findings indicate that in young‐onset MCI, the relationship between WMH and GMV is determined by WMH load rather than hypertension status. WMH load also influences the relationship between systolic BP and GMV in young‐onset MCI. Importantly, our results suggest that WMH and hypertension influence GMV via different mechanisms and BP recommendations for dementia prevention may be different in MCI with and without WMH. [ABSTRACT FROM AUTHOR]

Background: Chronic cerebrovascular pathology accelerates the incidence of poststroke dementia (PSD). Whether the risk of PSD varies according to different types of chronic cerebrovascular pathology remains unclear.Objectives: We investigated whether PSD is associated with a unique pattern of interactions between chronic cerebrovascular pathologies and acute stroke lesions.Materials and Method: In this case-control study of acute mild stroke patients (n=185), cases included patients who developed PSD at a 6-month poststroke follow-up, and controls included patients who remained nondemented at 6 months, matched on prestroke cognitive status. Magnetic resonance imaging was performed at initial stroke presentation; neuropsychological assessments were performed 6 months after the stroke.Results: White matter hyperintensities (WMH), chronic lacunes, microbleeds, and acute infarcts were not associated with PSD after controlling for demographics, cardiovascular risk, and global cortical atrophy. The risk of PSD was largest for patients with acute large subcortical infarcts (>15 mm) and concomitant periventricular WMH compared with patients with large subcortical infarcts and punctate/absent periventricular WMH [odds ratio (OR)=5.85, 95% confidence interval (CI)=1.85-40.04]. A moderate risk of PSD was observed for patients with acute multiple small infarcts (3 to 15 mm) and concomitant lacunes (OR=2.48, 95% CI=0.94-6.51) or concomitant lobar microbleeds (OR=2.20, 95% CI=0.89-5.41), compared with patients with acute multiple small infarcts and absent lacunes or microbleeds. Single small infarcts did not interact with cerebrovascular pathology to affect PSD.Conclusions: The risk of PSD varies depending on the presence of chronic cerebrovascular pathologies and type of acute infarcts. Clinical implications support a precision medicine approach for stratifying those at highest risk of PSD. [ABSTRACT FROM AUTHOR]

Background: Oligomeric Amyloid Beta (OAβ), is representative of a soluble, neurotoxic and pathogenic form of Aβ, which has been found to function as upstream drivers of Alzheimer's Disease pathology (Tolar et al., 2021). It serves as a contributory factor towards the formation of cortical Aβ plaques and neurofibrillary Tau tangles, and has been found to induce oxidative stress, synaptic toxicity and neuroinflammation (Tolar et al., 2021). The pathology culminates in neuronal dysfunction/death and resultant neurodegeneration which has been found to manifest clinically as symptoms of cognitive decline. OAβ has been found to correlate with the severity of cognitive performance, as well as brain volume reduction (An et al., 2017, Wang et al., 2017, Meng et al., 2019, Youn et al., 2019, Babapour Mofrad et al., 2021). Nevertheless, its effect on language neutral cognitive tests ‐ the novel Visual Cognitive Assessment Test (VCAT) developed and validated by our team of neurologist and neuropsychologists; remains to be evaluated (Kandiah et al., 2016, Lim et al., 2018, Low et al., 2020). Methods: A cross‐sectional pilot study was conducted in a cohort of 63 patients, clinically diagnosed with mild cognitive impairment (MCI). The patients underwent cognitive evaluation tests, Multimer Detection System (MDS) based plasma OAβ analysis and MRI based cortical grey matter evaluations (Wang et al., 2017, Youn et al., 2019, Pyun et al., 2021, Vipin et al., 2021). Pearson's correlation evaluated associations between plasma OAβ, cognitive scores [Mini‐Mental State Examination (MMSE), VCAT] and brain volume measures [Grey Matter Volume (GMV) / Intracranial Volume (ICV)]. Results: Increasing plasma OAβ expression associated with decreasing, VCAT scores (r = ‐0.291, 95% CI = ‐0.504 to ‐0.044, p = 0.022) and MMSE scores (r = ‐0.272, 95% CI = ‐0.489 to ‐0.024, p = 0.032), in MCI patients (Figure 1A, B). Additionally increasing plasma OAβ expression also associated with decreasing and GMV/ ICV ratio (r = ‐0.264, 95% CI = ‐0.489 to ‐0.007, p = 0.045), in MCI patients (Figure 1C). Conclusion: Findings from this study, emphasise on the promising clinical utility of plasma OAβ as a biomarker. Future longitudinal studies will validate these associations across the Alzheimer's disease spectrum. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH) are a known risk factor for cognitive decline (C.Puzo el. al. 2019). While the ε4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline in concomitance with WMH (D.Tsuang et. al. 2013), it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia. Our objective was thus to determine how APOE4 moderates the relationship between WMH and cognition in prodromal dementia. Method: 216 participants with prodromal dementia underwent magnetic resonance imaging (MRI), neuropsychological testing (global and domain‐specific), cardiovascular risk factor assessments and APOE genotyping. Visual ratings for WMH as well as total and lobar WMH volumes were quantified. Moderation analysis was performed to determine the influence of APOE4 on the relationship between WMH and performance on global and domain‐specific cognitive measures (executive function, episodic memory, attention, language) in moderation analysis (Figure 1). The role of confluent and non‐confluent WMH subtype on cognition was additionally studied using moderation analysis and logistic regression (Figure 1). Result: APOE4 carriers (n = 49) had poorer memory and higher global WMH (p = 0.04), temporal WMH (p = 0.01) and occipital WMH (p = 0.02) compared to APOE4 non‐carriers (n = 167). APOE4 strengthened the relationship between higher total WMH burden and worse episodic memory performance (Fig.2a). At the lobar WMH level, APOE4 strengthened associations between frontal, temporal, parietal and occipital WMH and episodic memory performance (Fig.2b, Fig.2c, Fig.2d, and Fig.2e) with large sized effects (β). APOE4 did not interact with either total or lobar WMH to predict worse cognition in other cognitive domains. Moreover, APOE4 strengthened the relationship between frontal WMH with episodic memory in the confluent WMH subgroup (Fig.2f). Logistic regression model showed memory impairment was 4.81 times more likely to develop in patients carrying APOE4 and with confluent WMH compared to APOE4 non‐carriers and those with non‐confluent WMH (OR 4.81, β 1.57, p<0.01). Conclusion: The impact of WMH on memory may be strongest in APOE4 carriers at the prodromal dementia stage. Clinicians targeting WMH would need to consider the APOE4 allele and WMH severity status to strategize cognitive interventions. [ABSTRACT FROM AUTHOR]

Objective: Late-life depression involves the disconnection of white matter tracts that regulate mood. A pathogenic link between poor tract integrity and depressive symptoms is believed to be white matter lesions (WML), however the mechanisms linking tract integrity, WML, and depression remains unexplored. The authors sought to identify whether the association between reduced tract integrity and depressive symptoms is mediated by WML in patients with Alzheimer disease (AD), and whether individual characteristics moderate this effect.Methods: This was a cross-sectional study in a tertiary memory clinic. A total of 91 patients with mild AD and 79 healthy elderly, comparable in depressive symptoms, white matter hyperintensities (WMH) volume, cardiovascular risk, age, and sex were chosen. Tract integrity was assessed using diffusion tensor imaging, WML were indexed as WMH, measured using fluid-attenuation inversion recovery imaging, and depressive symptoms were measured with the informant-based Geriatric Depression Scale.Results: In patients with mild AD, reduced tract integrity in right hemispheric cortical-subcortical tracts and the genu of the corpus callosum was moderately associated with depressive symptoms. This association was fully mediated by WML. Moderation analysis indicated that old age strengthened the association between all tracts and depressive symptoms, as mediated by WML. In cognitively healthy elderly, neither tracts nor WML were related to depressive symptoms.Conclusion: Reduced tract integrity may be important but not sufficient for the manifestation of depressive symptoms in mild AD. Instead, WML may drive the pathogenic link between reduced tract integrity and depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Mild behavioral impairment (MBI) describes the emergence of neurobehavioral symptoms in later life as harbingers of neurodegeneration. Emerging evidence suggests that white matter hyperintensity (WMH), a known risk factor for cognitive impairment, is associated with MBI. Furthermore, education level which reflects cognitive reserve, influences the risk of dementia. However, the role of education levels on the relationship between WMH and MBI is unknown. Here, we aim to evaluate the effects of education levels on WMH and MBI among a pre‐dementia cohort from a memory clinic in Singapore. Method: In this retrospective cross‐sectional study, 210 pre‐dementia participants (mean age 64.31, mean MMSE 27.77, mean education level 12.60, 37.6% males), underwent cognitive assessment, Magnetic Resonance Imaging (MRI) and completed the MBI‐checklist (MBI‐C) self‐report in National Neuroscience Institute Singapore from 2017 to 2021. Multiple linear regression models evaluated the main effects of WMH total ratings and years of education on MBI, while moderation analysis evaluated the effects of years of education with WMH on MBI. All analyses were controlled for age and sex. Result: While education levels and WMH were not associated with MBI‐C total scores independently (p>0.05), we found that education levels moderated the effects of WMH on MBI‐C total score (β=0.269 , p=0.038). Specifically, higher education attainment is associated with lower MBI‐C total scores among individuals with lower burden of WMH; while higher MBI‐C total score is observed with higher education among people with high WMH burden (Figure 1). Conclusion: Higher education attainment is associated with a lower risk of MBI when the WMH load is lower. Our findings support interventions to reduce WMH load in pre‐dementia people with higher education attainment to reduce MBI severity. [ABSTRACT FROM AUTHOR]

Background: Oligomeric amyloid‐beta (OAβ) is postulated to be the major neurotoxic species that is implicated in the pathophysiology of Alzheimer's disease (AD). Emerging evidence suggest that plasma OAβ levels are higher in AD compared to cognitively unimpaired individuals and correlate well with AD biomarkers. Diabetes Mellitus (DM) is consistently linked to cognitive dysfunction and epidemiological studies show that patients with DM have an increased risk of AD. While cerebral amyloid deposition is hypothesized to be the link between AD and DM, the association of OAβ and DM on cognition among mild cognitive impairment (MCI) remains unknown. Here, we aim to evaluate the effects of plasma OAβ levels and DM on cognition among MCI patients from a memory clinic in Singapore. Method: In this retrospective cross‐sectional study, 54 MCI patients (mean age 68.31, 44.4% males) stratified by DM diagnosis, underwent cognitive assessment and plasma OAβ measurements using the Multimer Detection System‐Oligomeric Aβ (MDS‐OAβ) in National Neuroscience Institute Singapore between 2019 to 2021. Multiple linear regression models evaluated the main effects of OAβ and DM on cognition while mediation analysis evaluated the effect of DM on cognition mediated via OAβ. All analyses were controlled for age, sex, education. Result: 13 (24.1%) of the total MCI cohort had DM and OAβ levels were higher in DM patients (0.68 vs 0.53 ng/ml, p=0.023).OAβ levels were associated with lower MMSE scores (β= ‐4.08, p=0.004) while DM was associated with lower MMSE (β = ‐1.26, p=0.046) and MoCA (β = ‐1.83, p=0.025) scores. Plasma OAβ partially mediates the effect of DM on MoCA scores (Figure 1). Conclusion: The effect of DM on poorer global cognition is partially mediated by higher plasma OAβ levels. While these results need to be replicated in a larger cohort, our findings suggest that optimizing DM control among MCI may reduce the burden of OAβ and improve cognition. [ABSTRACT FROM AUTHOR]

This is a case report of an atypical presentation of early onset Alzheimer disease (EOAD) in a young patient with Capgras syndrome and cognitive impairment. The concurrent onset of psychiatric and cognitive symptoms prompted a detailed evaluation for a neurodegenerative disease. A 50-year-old male lawyer presented with low mood, apathy, delusions, and auditory hallucinations over 18 months. He considered his wife as an imposter and would require her text message to confirm her identity. He became more forgetful and had to give up his law practice. His neuropsychological assessment was impaired in all domains. Genetic testing revealed homozygosity for APOEe4 alleles. His magnetic resonance imaging showed predominant parietal and medial temporal atrophy, [18F]Fluorodeoxyglucose positron emission tomography showed frontal, parietal and posterior temporal hypometabolism and [18F]Flutemetamol positron emission tomography was positive for amyloid deposition, leading to the diagnosis of EOAD. This case highlights EOAD as a differential diagnosis in young patients who present with Capgras syndrome. [ABSTRACT FROM AUTHOR]

Background: With increasing research into novel disease modifying therapies for mild cognitive impairment (MCI) and mild dementia, there is a need for large scale early detection of cognitive disorders. However, existing cognitive evaluation tools largely cater for native English speakers. We designed and validated a novel visual based cognitive evaluation tool that could be applied to multilingual populations worldwide without the need for translation. Methods: The development of the VCAT included pilot testing of individual test items, test refinement and development of a field version of VCAT. The test items covered domains of episodic memory, executive function, visuospatial function, semantic language and attention. The initial validation was carried out in a single centre cohort from Singapore comprising of cognitively normal (CN), MCI and dementia participants. Subsequent validation was carried out in centres across four Southeast Asian countries including Singapore, Malaysia, Indonesia and Philippines. Additional evaluation of construct validity against comprehensive neuropsychological test battery has been performed. Further validation in Canada, Brazil, India and South Korea is on‐going. Results: In the initial single centre validation in a cohort of 206 participants with a mean age of 67.8 (8.86) years and mean years of education of 10.5(6.0), the area under the curve (AUC) of VCAT for detection of cognitive impairment, CI (MCI and mild dementia) was 93.3 (95% CI 90.1 to 96.4). The Se and Sp of VCAT for the diagnosis of CI were 85.6% and 81.1%, respectively. In a wider Southeast Asian multicentre cohort of 284 participants, VCAT had an AUC of 90.5 (95% CI 87.0‐94.0) in discriminating CN from CI. The multiple languages used to administer VCAT in the four countries did not significantly influence test scores. VCAT and its subdomains demonstrated good construct validity in terms of both convergent and divergent validity and good internal consistency (α =.74). Mean time‐to‐complete VCAT was 15.7 ± 7.3 min. Conclusions: The VCAT without the need for translation in multilingual populations has demonstrated high accuracy for the detection of MCI and mild dementia. [ABSTRACT FROM AUTHOR]

Background: Mild Behavioural Impairment‐Checklist (MBI‐C) is a validated questionnaire that measures sustained later‐life emergent neuropsychiatric symptoms among people with prodromal dementia. Using this checklist as a MBI case ascertainment instrument, the prevalence of MBI was found to be 5.8% in subjective cognitive decline (SCD) and 14.2% in mild cognitive impairment (MCI). While the MBI‐C can be self‐administered or administered through a close informant via face‐to‐face or phone interviews, it is unknown whether patients and close‐informants differentially report on the MBI‐C. Here, we aim to examine the differences in self‐administered and close‐informant administered MBI‐C scores in a specialty clinic population. Method: 87 (25 SCD and 62 MCI) patients from the Singapore National Neuroscience Institute memory clinic completed the MBI‐C and Geriatric Depression Scale (GDS)4. Close‐informants completed the MBI‐C and Zarit caregiver burden scale (Zarit)5. The MBI‐C is a 34‐item questionnaire organized into five domains; 1) motivation, 2) emotional regulation, 3) impulse control, 4) social cognition, and 5) abnormal thoughts. MBI is defined by an MBI‐C total score of >6.5 in MCI 3 and a >8.5 total score in SCI2. Paired sample T‐test evaluated the difference in MBI‐C scores between patients and close‐informants. Pearson correlation test evaluated the associations between MBI‐C with GDS and Zarit scores. Result: Out of 87 participants (Mage= 67.62, SD=9.08), 29 participants were diagnosed with MBI. The frequency of MBI did not differ between SCI and MCI (40% in SCI and 30% in MCI). We found that MBI‐C domain scores did not differ significantly between patients and close‐informants (p>0.05). GDS scores positively correlated with MBI total score (p<0.01), motivation (p<0.01), emotional regulation (p<0.01), impulse control (p<0.01), social cognition (p=0.001) and abnormal thoughts (p=0.018). Zarit scores positively correlated with MBI total score (p=0.017) and impulse control (p=0.009). Conclusion: MBI is common in our Asian clinic population with preclinical prodromal dementia diagnosed using the MBI‐C and was associated with greater caregiver burden and depressive symptoms. Importantly, we found that patients and their close‐informants do not report differently on the MBI‐C. Our findings suggest that both patients and close‐informants may provide reliable measures of the patient's neuropsychiatric symptoms using the MBI‐C. [ABSTRACT FROM AUTHOR]

Background: Mild Behavioural Impairment‐Checklist (MBI‐C) is a validated questionnaire that measures sustained later‐life emergent neuropsychiatric symptoms among people with prodromal dementia. Using this checklist as a MBI case ascertainment instrument, the prevalence of MBI was found to be 5.8% in subjective cognitive decline (SCD) and 14.2% in mild cognitive impairment (MCI). While the MBI‐C can be self‐administered or administered through a close informant via face‐to‐face or phone interviews, it is unknown whether patients and close‐informants differentially report on the MBI‐C. Here, we aim to examine the differences in self‐administered and close‐informant administered MBI‐C scores in a specialty clinic population. Method: 87 (25 SCD and 62 MCI) patients from the Singapore National Neuroscience Institute memory clinic completed the MBI‐C and Geriatric Depression Scale (GDS)4. Close‐informants completed the MBI‐C and Zarit caregiver burden scale (Zarit)5. The MBI‐C is a 34‐item questionnaire organized into five domains; 1) motivation, 2) emotional regulation, 3) impulse control, 4) social cognition, and 5) abnormal thoughts. MBI is defined by an MBI‐C total score of >6.5 in MCI 3 and a >8.5 total score in SCI2. Paired sample T‐test evaluated the difference in MBI‐C scores between patients and close‐informants. Pearson correlation test evaluated the associations between MBI‐C with GDS and Zarit scores. Result: Out of 87 participants (Mage= 67.62, SD=9.08), 29 participants were diagnosed with MBI. The frequency of MBI did not differ between SCI and MCI (40% in SCI and 30% in MCI). We found that MBI‐C domain scores did not differ significantly between patients and close‐informants (p>0.05). GDS scores positively correlated with MBI total score (p<0.01), motivation (p<0.01), emotional regulation (p<0.01), impulse control (p<0.01), social cognition (p=0.001) and abnormal thoughts (p=0.018). Zarit scores positively correlated with MBI total score (p=0.017) and impulse control (p=0.009). Conclusion: MBI is common in our Asian clinic population with preclinical prodromal dementia diagnosed using the MBI‐C and was associated with greater caregiver burden and depressive symptoms. Importantly, we found that patients and their close‐informants do not report differently on the MBI‐C. Our findings suggest that both patients and close‐informants may provide reliable measures of the patient's neuropsychiatric symptoms using the MBI‐C. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that confluent WMH results in greater cognitive impairment compared to non‐confluent WMH. However, the mechanism linking confluent WMH and early cognitive impairment is not clearly understood. We studied the effects of confluent and non‐confluent WMH on whole‐brain functional connectivity (FC) across 164 regions of interest (ROI) in subjects with Mild Cognitive Impairment (MCI). Method: Sixty‐three MCI subjects with T1‐weighted MRI, T2‐weighted MRI, resting‐state functional MRI (rs‐fMRI) and neuropsychological data were studied. Subjects were classified as confluent WMH (C‐WMH) or non‐confluent WMH (NC‐WMH) using the Staal's criteria on the Fazekas WMH scale. Group‐level ROI‐to‐ROI FC trends and differences at differential WMH subtypes were computed using standard rs‐fMRI analysis. Result: Subjects with C‐WMH exhibited increased inter‐regional FC in the fronto‐parietal, fronto‐occipital, parieto‐occipital, and temporo‐parietal regions of the salience, dorsal‐attention, default‐mode, and visual networks. Increased intra‐regional FC in the frontal lobe was also observed in C‐WMH. In contrast, only intra‐regional FC changes were seen in the frontal and temporal lobes in NC‐WMH. Performance on the Montreal Cognitive Assessment correlated positively with increased inter‐regional FC only in the C‐WMH group, suggesting that increased connectivity was associated with better global cognition in MCI subjects with C‐WMH. Conclusion: C‐WMH in subjects with MCI is associated with widespread increased inter‐regional FC changes which correlates with better performance in global cognition. These findings provide novel insights into divergent functional alterations related to the confluence of WMH in MCI. [ABSTRACT FROM AUTHOR]

Background: Mild Behavioural Impairment (MBI) is a neurobehavioral syndrome characterized by later‐life emergent and sustained neuropsychiatric symptoms that is associated with higher risk of incident cognitive decline and dementia. While MBI is common in both subjective and mild cognitive impairment (MCI), most findings are based on Caucasians and the literature of MBI among Asians remains sparse. Here, we aim to investigate the frequency of MBI and its relationship with cognition, sleep and mood symptoms among cognitively intact (CN) and MCI Asians. Method: 162 subjects (80 CN and 82 MCI) with a Clinical Dementia Rating of 0 or 0.5 were recruited from an outpatient neurology clinic (National Neuroscience Institute, Singapore). All subjects were administered a comprehensive neuropsychological assessment, the Pittsburgh Sleep Quality Index (PSQI) and the MBI‐checklist (MBI‐C). The presence of MBI was determined based on published cut‐offs of 6.5 for MCI and 8.5 for CN. Regression models evaluated the relationships between MBI and cognition, sleep and mood. Result: 29 out of 162 subjects (17.9%) had MBI (28.0% of MCI and 7.5% of CN). Subjects with MBI had poorer global cognition (p=.029) and attention/working memory (p=.049). Specifically, we found that interest and impulse control subdomains of the MBI‐C were associated with poorer performance on the global cognition tests. In addition, those with MBI had sleep‐related daytime dysfunction (p=.008), poorer GDS and DASS scores (p<.01 or p<.001). Conclusion: MBI in common among our Asian cohort and is associated with poorer cognitive performance, sleep and mood symptoms. Our findings further support the utility of MBI in clinical practice to identify individuals with early presentation of neurodegenerative diseases so as to provide a window of opportunity for early interventions to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Mild Behavioural Impairment (MBI) is a neurobehavioral syndrome characterized by later‐life emergent and sustained neuropsychiatric symptoms that is associated with higher risk of incident cognitive decline and dementia. While MBI is common in both subjective and mild cognitive impairment (MCI), most findings are based on Caucasians and the literature of MBI among Asians remains sparse. Here, we aim to investigate the frequency of MBI and its relationship with cognition, sleep and mood symptoms among cognitively intact (CN) and MCI Asians. Method: 162 subjects (80 CN and 82 MCI) with a Clinical Dementia Rating of 0 or 0.5 were recruited from an outpatient neurology clinic (National Neuroscience Institute, Singapore). All subjects were administered a comprehensive neuropsychological assessment, the Pittsburgh Sleep Quality Index (PSQI) and the MBI‐checklist (MBI‐C). The presence of MBI was determined based on published cut‐offs of 6.5 for MCI and 8.5 for CN. Regression models evaluated the relationships between MBI and cognition, sleep and mood. Result: 29 out of 162 subjects (17.9%) had MBI (28.0% of MCI and 7.5% of CN). Subjects with MBI had poorer global cognition (p=.029) and attention/working memory (p=.049). Specifically, we found that interest and impulse control subdomains of the MBI‐C were associated with poorer performance on the global cognition tests. In addition, those with MBI had sleep‐related daytime dysfunction (p=.008), poorer GDS and DASS scores (p<.01 or p<.001). Conclusion: MBI in common among our Asian cohort and is associated with poorer cognitive performance, sleep and mood symptoms. Our findings further support the utility of MBI in clinical practice to identify individuals with early presentation of neurodegenerative diseases so as to provide a window of opportunity for early interventions to improve clinical outcomes. [ABSTRACT FROM AUTHOR]