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Article ; Online: Linking statins and lipids in Parkinson's disease.

Ng, Adeline S L / Tan, Eng-King

Movement disorders : official journal of the Movement Disorder Society

2017 Volume 32, Issue 6, Page(s) 807–809

MeSH term(s)	Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipids ; Parkinson Disease
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipids
Language	English
Publishing date	2017-05-27
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.27053
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Article ; Online: Plasma Soluble ST2 Levels Are Higher in Neurodegenerative Disorders and Associated with Poorer Cognition.

Tan, Yi Jayne / Siow, Isabel / Saffari, Seyed Ehsan / Ting, Simon K S / Li, Zeng / Kandiah, Nagaendran / Tan, Louis C S / Tan, Eng King / Ng, Adeline S L

Journal of Alzheimer's disease : JAD

2023 Volume 92, Issue 2, Page(s) 573–580

Abstract: Background: Suppressor of tumorgenicity 2 (ST2) is highly expressed in brain tissue and is a receptor for interleukin 33 (IL-33). ST2 exists in two forms, a transmembrane receptor (ST2L) and a soluble decoy receptor (sST2). IL-33 binds to ST2L, ... ...

Abstract	Background: Suppressor of tumorgenicity 2 (ST2) is highly expressed in brain tissue and is a receptor for interleukin 33 (IL-33). ST2 exists in two forms, a transmembrane receptor (ST2L) and a soluble decoy receptor (sST2). IL-33 binds to ST2L, triggering downstream signaling pathways involved in amyloid plaque clearance. Conversely, sST2 binds competitively to IL-33, attenuating its neuroprotective effects. High sST2 levels have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), suggesting that the IL-33/ST2 signaling pathway may be implicated in neurodegenerative diseases. Objective: To investigate plasma sST2 levels in controls and patients with MCI, AD, frontotemporal dementia (FTD), and Parkinson's disease (PD). Methods: Plasma sST2 levels were measured using ELISA in 397 subjects (91 HC, 46 MCI, 38 AD, 28 FTD, and 194 PD). Cerebrospinal fluid (CSF) levels of sST2 were measured in 22 subjects. Relationship between sST2 and clinical outcomes were analyzed. Results: Plasma sST2 levels were increased across all disease groups compared to controls, with highest levels seen in FTD followed by AD and PD. Dementia patients with higher sST2 had lower cross-sectional cognitive scores in Frontal Assessment Battery and Digit Span Backward. At baseline, PD-MCI patients had higher sST2, associated with worse attention. In the longitudinal PD cohort, higher sST2 significantly associated with decline in global cognition and visuospatial domains. Plasma sST2 levels correlated with CSF sST2 levels. Conclusion: Plasma sST2 is raised across neurodegenerative diseases and is associated with poorer cognition. Higher baseline sST2 is a potential biomarker of disease severity in neurodegeneration.
MeSH term(s)	Humans ; Interleukin-33/metabolism ; Interleukin-1 Receptor-Like 1 Protein/metabolism ; Frontotemporal Dementia/cerebrospinal fluid ; Cross-Sectional Studies ; Alzheimer Disease/psychology ; Biomarkers/cerebrospinal fluid ; Cognition ; Parkinson Disease
Chemical Substances	Interleukin-33 ; Interleukin-1 Receptor-Like 1 Protein ; Biomarkers
Language	English
Publishing date	2023-02-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-221072
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Article ; Online: Teaching NeuroImages: Linear Radial Periventricular Enhancement in Glial Fibrillary Acidic Protein Astrocytopathy.

Kong, Yongyao / McKeon, Andrew / Koh, Odelia S Q / Chiew, Yi Rong / Purohit, Bela / Chin, Chee Fang / Zekeridou, Anastasia / Ng, Adeline S L

Neurology

2021 Volume 96, Issue 19, Page(s) e2454–e2455

MeSH term(s)	Adrenal Cortex Hormones/pharmacology ; Astrocytes/pathology ; Autoantibodies/cerebrospinal fluid ; Brain/diagnostic imaging ; Brain/drug effects ; Brain/metabolism ; Female ; Glial Fibrillary Acidic Protein/cerebrospinal fluid ; Humans ; Magnetic Resonance Imaging/methods ; Meningoencephalitis/cerebrospinal fluid ; Meningoencephalitis/diagnostic imaging ; Meningoencephalitis/drug therapy ; Middle Aged ; Spinal Cord/diagnostic imaging ; Spinal Cord/drug effects ; Spinal Cord/metabolism
Chemical Substances	Adrenal Cortex Hormones ; Autoantibodies ; GFAP protein, human ; Glial Fibrillary Acidic Protein
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000011496
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Article ; Online: Feasibility, comprehensibility and acceptability of the VISION-Cog, a novel tool to assess cognitive impairment in visually impaired older adults: a cross-sectional pilot study in Singapore.

Vu, Tai Anh / Fenwick, Eva / Doshi, Kinjal / Gupta, Preeti / Quek, Shin Yi / Chen, Christopher / Ting, Simon / Ng, Adeline S L / Yap, Philip / Yeo, Donald / Milea, Dan / Lamoureux, Ecosse

BMJ open

2023 Volume 13, Issue 9, Page(s) e072151

Abstract: Objectives: We pilot-tested the : 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 ... ...

Abstract	Objectives: We pilot-tested the 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.
MeSH term(s)	Humans ; Aged ; Pilot Projects ; Cross-Sectional Studies ; Feasibility Studies ; Singapore ; Vision, Low ; Cognitive Dysfunction/diagnosis
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-072151
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Article ; Online: Content development of the VISION-Cog: a novel tool to assess cognitive impairment in visually impaired older adults in Singapore.

Vu, Tai Anh / Fenwick, Eva / Doshi, Kinjal / Gupta, Preeti / Quek, Shin Yi / Chen, Christopher / Ting, Simon / Ng, Adeline S L / Yap, Philip / Yeo, Donald / Milea, Dan / Lamoureux, Ecosse Luc

BMJ open

2023 Volume 13, Issue 10, Page(s) e070850

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Aged ; Singapore ; Cognitive Dysfunction/diagnosis ; Cognition Disorders/diagnosis ; Cognition ; Executive Function ; Neuropsychological Tests
Language	English
Publishing date	2023-10-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-070850
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Article ; Online: Feasibility, comprehensibility and acceptability of the VISION-Cog, a novel tool to assess cognitive impairment in visually impaired older adults

Preeti Gupta / Christopher Chen / Philip Yap / Dan Milea / Ecosse Lamoureux / Adeline S L Ng / Eva Fenwick / Kinjal Doshi / Tai Anh Vu / Shin Yi Quek / Simon Ting / Donald Yeo

BMJ Open, Vol 13, Iss

a cross-sectional pilot study in Singapore

2023 Volume 9

Abstract: ... cognitively normal participants aged ≥60 years to examine the pilot VISION-Cog’s feasibility (length of time ...

Abstract	Objectives We pilot-tested the VISually Independent test battery Of NeuroCOGnition (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.
Keywords	Medicine ; R
Subject code	150
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: C9orf72 expansions are the most common cause of genetic frontotemporal dementia in a Southeast Asian cohort.

Tan, Yi Jayne / Yong, Alisa C W / Foo, Jia Nee / Lian, Michelle M / Lim, Weng Khong / Dominguez, Jacqueline / Fong, Zhi Hui / Narasimhalu, Kaavya / Chiew, Hui Jin / Ng, Kok Pin / Ting, Simon K S / Kandiah, Nagaendran / Ng, Adeline S L

Annals of clinical and translational neurology

2023 Volume 10, Issue 4, Page(s) 568–578

Abstract: Objective: Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative disorders, including behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant PPA (nfvPPA). While a strong genetic ... ...

Abstract	Objective: Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative disorders, including behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant PPA (nfvPPA). While a strong genetic component is implicated in FTD, genetic FTD in Asia is less frequently reported. We aimed to investigate the frequency of Southeast Asian FTD patients harbouring known genetic FTD variants. Methods: A total of 60 FTD-spectrum patients (25 familial and 35 sporadic) from Singapore and the Philippines were included. All underwent next-generation sequencing and repeat-primed PCR for C9orf72 expansion testing. Neurofilament light chain (NfL) levels were measured in a subset of patients. Results: Overall, 26.6% (16/60 cases) carried pathogenic or likely pathogenic variants in a FTD-related gene, including: MAPT Gln351Arg (n = 1); GRN Cys92Ter (n = 1), Ser301Ter (n = 2), c.462 + 1G > C (n = 1); C9orf72 expansion (35-70 repeats; n = 8); TREM2 Arg47Cys (n = 1); and OPTN frameshift insertion (n = 2). Genetic mutations accounted for 48% (12/25) of patients with familial FTD, and 11.4% (4/35) of patients with sporadic FTD. C9orf72 repeat expansions were the most common genetic mutation (13.3%, 8/60), followed by GRN (6.7%, 4/60) variants. Within mutation carriers, plasma NfL was highest in a C9orf72 expansion carrier, and CSF NfL was highest in a GRN splice variant carrier. Interpretation: In our cohort, genetic mutations are present in one-quarter of FTD-spectrum cases, and up to half of those with family history. Our findings highlight the importance of wider implementation of genetic testing in FTD patients from Southeast Asia.
MeSH term(s)	Humans ; Frontotemporal Dementia/genetics ; Frontotemporal Dementia/pathology ; C9orf72 Protein/genetics ; Southeast Asian People ; Pick Disease of the Brain ; Mutation
Chemical Substances	C9orf72 Protein ; C9orf72 protein, human
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51744
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Article ; Online: Content development of the VISION-Cog

Preeti Gupta / Ecosse Luc Lamoureux / Christopher Chen / Philip Yap / Dan Milea / Adeline S L Ng / Eva Fenwick / Kinjal Doshi / Tai Anh Vu / Shin Yi Quek / Simon Ting / Donald Yeo

BMJ Open, Vol 13, Iss

a novel tool to assess cognitive impairment in visually impaired older adults in Singapore

2023 Volume 10

Abstract: 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 ...

Abstract	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 ...
Keywords	Medicine ; R
Subject code	150
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Longitudinal Study of SNCA Rep1 Polymorphism on Executive Function in Early Parkinson's Disease.

Tan, Yi Jayne / Saffari, Seyed Ehsan / Zhao, Yi / Ng, Ebonne Y L / Yong, Alisa C W / Ng, Samuel Y E / Chia, Nicole S Y / Choi, Xinyi / Heng, Dede / Neo, Shermyn / Xu, Zheyu / Tay, Kay Yaw / Au, Wing Lok / Tan, Eng-King / Tan, Louis C S / Ng, Adeline S L

Journal of Parkinson's disease

2022 Volume 12, Issue 3, Page(s) 865–870

Abstract: The alpha-synuclein gene promoter (SNCA-Rep1) is associated with Parkinson's disease (PD), but its relationship with performance across individual cognitive domains in early PD is unknown. This study aims to investigate Rep1 polymorphism and longitudinal ...

Abstract	The alpha-synuclein gene promoter (SNCA-Rep1) is associated with Parkinson's disease (PD), but its relationship with performance across individual cognitive domains in early PD is unknown. This study aims to investigate Rep1 polymorphism and longitudinal change in cognition in early PD. In this longitudinal study, Rep1 allele lengths ("long" and "short") were determined in 204 early PD patients. All participants underwent annual neuropsychological assessments and followed up for 3 years. Linear-mixed model was performed to investigate the association of Rep1 status and longitudinal change in individual cognitive domains. At 3 years, significant decline in executive function was observed in long Rep1 allele carriers vs short allele carriers, controlling for potential confounders. This is the first longitudinal study demonstrating that long Rep1 allele carriers are at higher risk for executive dysfunction in early PD.
MeSH term(s)	Executive Function ; Genetic Predisposition to Disease ; Humans ; Longitudinal Studies ; Parkinson Disease/complications ; Parkinson Disease/genetics ; Polymorphism, Genetic ; alpha-Synuclein/genetics
Chemical Substances	SNCA protein, human ; alpha-Synuclein
Language	English
Publishing date	2022-01-23
Publishing country	Netherlands
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-213029
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Article ; Online: Altered Cerebrospinal Fluid Exosomal microRNA Levels in Young-Onset Alzheimer's Disease and Frontotemporal Dementia.

Tan, Yi Jayne / Wong, Benjamin Y X / Vaidyanathan, Ramanathan / Sreejith, Sivaramapanicker / Chia, Sook Yoong / Kandiah, Nagaendran / Ng, Adeline S L / Zeng, Li

Journal of Alzheimer's disease reports

2021 Volume 5, Issue 1, Page(s) 805–813

Abstract: Background: micro-RNAs (miRNAs) are stable, small, non-coding RNAs enriched in exosomes. Their variation in levels according to different disease etiologies have made them a promising diagnostic biomarker for neurodegenerative diseases such as Alzheimer' ...

Abstract	Background: micro-RNAs (miRNAs) are stable, small, non-coding RNAs enriched in exosomes. Their variation in levels according to different disease etiologies have made them a promising diagnostic biomarker for neurodegenerative diseases such as Alzheimer's disease (AD). Altered expression of miR-320a, miR-328-3p, and miR-204-5p have been reported in AD and frontotemporal dementia (FTD). Objective: To determine their reliability, we aimed to examine the expression of three exosomal miRNAs isolated from cerebrospinal fluid (CSF) of patients with young-onset AD and FTD (< 65 years), correlating with core AD biomarkers and cognitive scores. Methods: Exosomes were first isolated from CSF samples of 48 subjects (8 controls, 28 AD, and 12 FTD), followed by RNA extraction and quantitative PCR to measure the expression of miR-320a, miR-328-3p, and miR-204-5p. Results: Expression of all three markers (miR-320a ( Conclusion: Overall, we demonstrated miR-320a and miR-204-5p as reliable biomarkers for AD and FTD and report miR-328-3p as a novel AD biomarker.
Language	English
Publishing date	2021-10-28
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-210311
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