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Competing Interests: The authors declared no conflict of interest.

Objectives: Current cognitive screening and diagnostic instruments rely on visually dependent tasks and are, therefore, not suitable to assess cognitive impairment (CI) in visually impaired older adults. We describe the content development of the VISually Independent test battery Of NeuroCOGnition (VISION-Cog)-a new diagnostic tool to evaluate CI in visually impaired older Singaporean adults., Design: The content development phase consisted of two iterative stages: a neuropsychological consultation and literature review (stage 1) and an expert-panel discussion (stage 2). In stage 1, we investigated currently available neuropsychological test batteries for CI to inform constructions of our preliminary test battery. We then deliberated this battery during a consensus meeting using the Modified Nominal Group technique (stage 2) to decide, via agreement of five experts, the content of a pilot neuropsychological battery for the visually impaired., Setting: Singapore Eye Research Institute., Participants: Stakeholders included researchers, psychologists, neurologists, neuro-ophthalmologists, geriatricians and psychiatrists., Outcome Measure: pilot VISION-Cog., Results: The two-stage process resulted in a pilot VISION-Cog consisting of nine vision-independent neuropsychological tests, including the modified spatial memory test, list learning, list recall and list recognition, adapted token test, semantic fluency, modified spatial analysis, verbal subtests of the frontal battery assessment, digit symbol, digit span forwards, and digit span backwards. These tests encompassed five cognitive domains-memory and learning, language, executive function, complex attention, and perceptual-motor abilities. The expert panel suggested improvements to the clarity of test instructions and culturally relevant test content. These suggestions were incorporated and iteratively pilot-tested by the study team until no further issues emerged., Conclusions: We have developed a five-domain and nine-test VISION-Cog pilot instrument capable of replacing vision-dependent diagnostic batteries in aiding the clinician-based diagnosis of CI in visually impaired older adults. Subsequent phases will examine the VISION-Cog's feasibility, comprehensibility and acceptability; and evaluate its diagnostic performance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We pilot-tested the VIS ually I ndependent test battery O f N euro COG nition (VISION-Cog) to determine its feasibility, comprehensibility and acceptability in evaluating cognitive impairment (CI) in visually impaired older Asian adults., Design: The VISION-Cog was iteratively fine-tuned through pilot studies and expert-panel discussion. In the first pilot study (Stage 1), we recruited 15 visually impaired and cognitively normal participants aged ≥60 years to examine the pilot VISION-Cog's feasibility (length of time to administer), comprehensibility (clarity of instructions) and acceptability (participant burden). We then presented the pilot results to the expert panel (Stage 2) who decided via agreement on a revised version of the VISION-Cog. Subsequently, we conducted a second pilot study (Stage 3) on another four participants to ascertain improvement in feasibility, comprehensibility and acceptability of the revised version., Setting: Singapore Eye Research Institute., Participants: Nineteen Asian adults aged ≥60 years with visual impairment (defined as near visual acuity worse than N8) were recruited., Outcome Measure: Revised VISION-Cog., Result: The VISION-Cog was deemed feasible, taking approximately 60 min to complete on average. All participants agreed that the test instructions were clear, and the battery did not cause undue discomfort or frustration. The data collector rated all tests as very user-friendly (score of 5/5). Minor modifications to the pilot VISION-Cog were suggested by the panel to improve its safety, clarity of instructions and content validity, which were incorporated and iteratively tested in the second pilot study until no further issues emerged., Conclusions: Using an iterative mixed-methods process, we have developed a feasible, comprehensible and acceptable 5-domain and 9-item visually independent VISION-Cog test battery suitable to assist CI diagnosis in older adults with visual impairment. We will assess its diagnostic potential against clinician-based assessment of CI in subsequent phases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort., Methods: Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed., Results: 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age < 50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser)., Conclusion: Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.

Background: The use of structural and perfusion brain imaging in combination with behavioural information in the prediction of cognitive syndromes using a data-driven approach remains to be explored. Here, we thus examined the contribution of brain structural and perfusion imaging and behavioural features to the existing classification of cognitive syndromes using a data-driven approach. Methods: Study participants belonged to the community-based Biomarker and Cognition Cohort Study in Singapore who underwent neuropsychological assessments, structural-functional MRI and blood biomarkers. Participants had a diagnosis of cognitively normal (CN), subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and dementia. Cross-sectional structural and cerebral perfusion imaging, behavioural scale data including mild behaviour impairment checklist, Pittsburgh Sleep Quality Index and Depression, Anxiety and Stress scale data were obtained. Results: Three hundred seventy-three participants (mean age 60.7 years; 56% female sex) with complete data were included. Principal component analyses demonstrated that no single modality was informative for the classification of cognitive syndromes. However, multivariate glmnet analyses revealed a specific combination of frontal perfusion and temporo-frontal grey matter volume were key protective factors while the severity of mild behaviour impairment interest sub-domain and poor sleep quality were key at-risk factors contributing to the classification of CN, SCI, MCI and dementia (p < 0.0001). Moreover, the glmnet model showed best classification accuracy in differentiating between CN and MCI cognitive syndromes (AUC = 0.704; sensitivity = 0.698; specificity = 0.637). Conclusions: Brain structure, perfusion and behavioural features are important in the classification of cognitive syndromes and should be incorporated by clinicians and researchers. These findings illustrate the value of using multimodal data when examining syndrome severity and provide new insights into how cerebral perfusion and behavioural impairment influence classification of cognitive syndromes. [ABSTRACT FROM AUTHOR]

Background: A delay in the detection of mild cognitive impairment (MCI) in the community delays the opportunity for early intervention. Accurate tools to detect MCI in the community are lacking. The Visual Cognitive Assessment Test (VCAT) is a visual based cognitive test useful for multilingual populations without the need for translation. Objective: Here, we evaluate the usefulness of VCAT in detecting MCI in a community population in Singapore. Methods: We recruited 301 participants from the community who completed a detailed neuropsychological assessment and 170 of them completed a 3T magnetic resonance imaging (MRI) brain scan. We performed a receiver operating characteristics analysis to test the diagnostic performance of VCAT compared to Montreal Cognitive Assessment (MoCA) in distinguishing MCI from cognitively normal (CN) by measuring area under the curve (AUC). To test for the association of VCAT with structural MRI, we performed a Pearson's correlation analysis for VCAT and MRI variables. Results: We recruited 39 CN and 262 MCI participants from Dementia Research Centre (Singapore). Mean age of the cohort was 63.64, SD = 9.38, mean education years was 13.59, SD = 3.70 and majority were women (55.8%). VCAT was effective in detecting MCI from CN with an AUC of 0.794 (95% CI 0.723–0.865) which was slightly higher than MoCA 0.699 (95% CI 0.621–0.777). Among subjects with MCI, VCAT was associated with medial temporal lobe atrophy (ρ = –0.265, p = 0.001). Conclusions: The VCAT is useful in detecting MCI in the community in Singapore and may be an effective measure of neurodegeneration. [ABSTRACT FROM AUTHOR]