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  1. Yap KH, Sulaiman S
    Singapore Med J, 2009 Jul;50(7):e247-9.
    PMID: 19644610
    Pulmonary atelectasis may be caused by endobronchial lesions or by extrinsic compression of the bronchus. However, lung collapse due to compression from a thoracic aneurysm is uncommon. We report a 76-year-old hypertensive female patient who has pulmonary atelectasis due to an extrinsic compression from a descending thoracic aortic aneurysm, and discuss possible treatment options.
  2. Yap KH, Abdul Manan H, Sharip S
    Behav Brain Res, 2021 01 15;397:112888.
    PMID: 32882284 DOI: 10.1016/j.bbr.2020.112888
    This review aims to establish the cognitive processing of patients with attention-deficit hyperactive disorder (ADHD) across age. Functional magnetic resonance imaging (fMRI) studies on children and adult populations were conducted, thus delineating deficits that could have been maintained and ameliorated across age. This allowed for the examination of the correlation between patterns of brain activation and the corresponding development of functional heterogeneity in ADHD. A systematic literature search of fMRI studies on ADHD was conducted using the PubMed and Scopus electronic databases based on PRISMA guidelines. References and citations were verified in Scopus database. The present study has identified 14 studies on children, 16 studies on adults, and one study on both populations of ADHD consisting of 1371 participants. Functional heterogeneity is present in ADHD across age, which can manifest either as different brain activation patterns, intra-subject variability, or both. This is shown in the increased role of the frontal regions and the specialized network in adults with ADHD from inefficient non-specific activation in childhood. Functional heterogeneity may manifest when delayed maturation is insufficient to normalize frontal lobe functions.
  3. Yap KH, Warren N, Allotey P, Reidpath D
    Front Neurol, 2021;12:628876.
    PMID: 34149589 DOI: 10.3389/fneur.2021.628876
    Following stroke, individuals require ongoing screening, diagnosis and monitoring for cognitive impairment. Services and policies around these vary widely between settings, and reports from many countries highlight persistent under-diagnosis of cognitive impairment in the months and years after stroke. Missed and delayed diagnosis of post-stroke cognitive impairment, including dementia, are important factors in shaping the experiences of people so affected and their family members, especially in low- and middle-income countries. Drawing upon ethnographic research conducted in Malaysia, this article draws upon three case studies to examine the continued health-seeking behaviour after the appearance of salient cognitive and behavioural symptoms that occurred after stroke. Findings highlight the challenges in getting formal diagnostic clarity for cognitive and behavioural symptoms in a rural setting within a middle-income country. No study participants sought help for memory or cognitive problems, partly due to limited lay awareness of cognitive impairment but more significantly due to health service factors. Despite their elevated risk for dementia, participants were not monitored for cognitive impairment during any follow-up care in various health facilities. Furthermore, caregivers' attempts to seek help when behavioural issues became untenable were met with multiple health system barriers. The journey was complicated by the meanings attached to the reactions towards cognitive symptoms at the community level. We suggest that strategies seek to increase the awareness of post-stroke cognitive and behavioural symptoms, and incorporate clear treatment pathways into the long-term care plans of community-dwelling stroke survivors.
  4. Yap KH, Warren N, Allotey P, Reidpath DD
    Aging Ment Health, 2020 05;24(5):709-716.
    PMID: 30588848 DOI: 10.1080/13607863.2018.1550632
    Background: Subjective memory complaints (SMC) are common in the elderly and have been suggested as the first subtle sign of decline which can predict dementia. Cognitive decline is thought to be related to inflammatory processes similarly found in other chronic diseases and conditions such as stroke, heart disease and arthritis. This study aimed to examine the association of SMC with chronic diseases and the profile of these health conditions reported by a group of older adults.Methods: Data from a cross-sectional survey conducted from August 2013 and March 2014 was drawn from 6179 individuals aged 56 years and above. Multivariable logistic regression analyses were used to examine SMC's relationship with individual chronic diseases (asthma, kidney disease, heart disease, stroke, arthritis, hypertension and diabetes) and multimorbidity. Latent class analysis (LCA) was used to identify the profile of health conditions. The effect of SMC was estimated in a multinomial logistic regression as part of the latent class model.Results: SMC was statistically significant in its association with asthma, stroke, heart disease, arthritis and multimorbidity in the fully controlled multivariable logistic regression models. Three health profiles were identified: low comorbidity (n = 4136, low rates in all health conditions), arthritis group (n = 860) and diabetes and hypertension group (n = 1183). SMC was associated with arthritis group (OR = 2.04, 95% CI = 1.51-2.75) and diabetes and hypertension group (OR = 1.22, 95% CI = 1.03-1.46).Conclusion: Adapting a combination of analytical approaches allows a better understanding in the assessment of SMC's relationship with chronic diseases and the patterns of distribution of these health conditions.
  5. Yap KH, Warren N, Allotey P, Reidpath DD
    Disabil Rehabil, 2021 02;43(3):345-353.
    PMID: 31169419 DOI: 10.1080/09638288.2019.1624841
    BACKGROUND: Stroke is a public health concern in Malaysia but local beliefs and lay understandings of stroke have not been examined before. Explanatory models provide a way for people to make sense of their illness and influence health seeking behaviors, in a locally relevant way.

    METHODS: Drawing on ethnographic research from rural Malaysia, this descriptive article explores ethnic Malaysian-Chinese stroke survivors' lay understandings of stroke. Eighteen community-dwelling stroke survivors aged 50-83 took part in the study.

    RESULTS: Causation of stroke was derived from cultural, biomedical and social sources. Participants also drew simultaneously from both biomedical and traditional explanations of stroke to develop their own understanding of etiology. Similarities with biomedical causation and other studies from different cultures were found. Participants' typically focused on the more immediate effects of stroke and often do not attribute causation and association with their comorbid conditions which are also risk factors of stroke.

    CONCLUSION: Lack of knowledge about stroke and its symptoms was evident in participants' account. Findings emphasize the importance of knowledge based health interventions, especially in health education strategies for stroke survivors to reduce delays to diagnosis and potentially improve health outcomes post-stroke. Implications for rehabilitation Stroke survivors often form explanatory models of stroke that draw from both biomedical and traditional explanations of stroke. Understanding how people derive lay understandings of stroke can contribute towards developing the goals and activities that facilitate recovery and rehabilitation in similar settings. Health practitioners in the community should strengthen communication regarding the identification, etiology and risk factors of stroke with stroke survivors and their carers to improve compliance to medication, exercise and diet for better recovery. Sustained health education which is culturally relevant is recommended. Communication should also include non-physical impact of stroke (such as cognitive deficits and emotional difficulties) as the stroke survivors were unlikely to relate such symptoms to stroke.

  6. Yap KH, Warren N, Reidpath DD, Allotey P
    Int J Qual Stud Health Well-being, 2019 Dec;14(1):1613875.
    PMID: 31120385 DOI: 10.1080/17482631.2019.1613875
    Purpose: Stroke survivors report poorer self-rated health (SRH) compared to the general population but there is limited understanding on what contributes to SRH. This ethnographic study examined the individual and contextual factors that shape stroke survivors' SRH in a rural middle income country situated in South East Asia. Methods: Ethnographic methods which encompasses various data collection methods from different data sources were used in this study to describe the socio-cultural context of 16 stroke survivors living in a rural village. Within this context, the experiences of these participants were then interpreted in terms of what contributed to their perception of health and recovery, juxtaposed with objectively measure physical and cognitive states. Results: SRH reflected the post stroke adjustment of stroke survivors. Better SRH was influenced by good post-stroke adjustment that was achieved by a combination of physical functioning, cognitive functioning, emotional well-being and family support. Poorer SRH appear to reflect poor post-stroke adjustment regardless of the objective physical and cognitive states of the stroke survivors. It was also observed that cognitive deficits, though its presence was acknowledged by participants, were usually not taken into account when rating SRH. However, while physical functioning was perceived by participants to directly impact SRH, the presence of cognitive deficits (often in tandem with depressive symptoms) indirectly complicated the recovery of physical functions treasured by participants. Conclusion: Stroke survivors reporting poorer SRH warrant further attention and intervention from health practitioners supporting the longer-term needs of stroke survivors in similar settings.
  7. Chuah SY, Tan WF, Yap KH, Tai HE, Chow ST
    Forensic Sci Int, 1994 Oct 21;68(3):169-80.
    PMID: 7982636
    The distributions of the D1S80 alleles and genotypes in the Chinese, Malays and Indians in Singapore were determined by amplified fragment length polymorphism (AMP-FLP) analysis. The distributions of the observed genotypes for the three races conformed to Hardy-Weinberg expectations. The system was applied to 19 families whose paternity had been established by restriction fragment length polymorphism (RFLP) analysis. In all cases, Mendelian inheritance of the alleles at the D1S80 locus could be demonstrated. D1S80 typing on DNA recovered by differential extraction of forensic specimens which included vaginal swabs, urethral swabs and seminal stains yielded consistent results.
  8. Yap KH, Yee GS, Candasamy M, Tan SC, Md S, Abdul Majeed AB, et al.
    Biomolecules, 2020 09 24;10(10).
    PMID: 32987623 DOI: 10.3390/biom10101360
    Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.
  9. Yap KH, Kessels RPC, Azmin S, van de Warrenburg B, Mohamed Ibrahim N
    Cerebellum, 2021 Jul 07.
    PMID: 34231180 DOI: 10.1007/s12311-021-01282-3
    Spinocerebellar ataxia type 3 (SCA3), the commonest dominantly inherited ataxia worldwide, is characterized by disruption in the cerebellar-cerebral and striatal-cortical networks. Findings on SCA3-associated cognitive impairments are mixed. The classification models, tests and scoring systems used, language, culture, ataxia severity, and depressive symptoms are all potential confounders in neuropsychological assessments and may have contributed to the heterogeneity of the neurocognitive profile of SCA3. We conducted a systematic review of studies evaluating neurocognitive function in SCA3 patients. Of 1304 articles identified, 15 articles met the eligibility criteria. All articles were of excellent quality according to the National Institutes of Health quality assessment tool for case-control studies. In line with the disrupted cerebellar-cerebral and striatal-cortical networks in SCA3, this systematic review found that the neurocognitive profile of SCA3 is characterized by a core impairment of executive function that affects processes such as nonverbal reasoning, executive aspects of language, and recall. Conversely, neurocognitive domains such as general intelligence, verbal reasoning, semantic aspect of language, attention/processing speed, recognition, and visuospatial perception and construction are relatively preserved. This review highlights the importance of evaluating neurocognitive function in SCA3 patients. Considering the negative impact of cognitive and affective impairment on quality of life, this review points to the profound impairments that existing or future treatments should prioritize.
  10. Yap KH, Mohan D, Stephan BCM, Warren N, Allotey P, Reidpath DD
    J Aging Res, 2019;2019:9151802.
    PMID: 31093373 DOI: 10.1155/2019/9151802
    Subjective memory complaints (SMCs) and social capital were known to be related to self-rated health (SRH). Despite this, no studies have examined the potential interaction of SMC and social capital on SRH. Using data from a cross-sectional health survey of men and women aged 56 years and above (n = 6,421), we examined how SMCs and social capital explained SRH in a population of community-dwelling older adults in a semirural area in Malaysia. We also evaluated whether SRH's relationship with SMCs is moderated by social capital. The association of SMC and social capital with poor SRH was investigated using multivariable logistic regression. Social capital (OR = 0.86, 95% CI = 0.82-0.89), mild SMC (OR = 1.70, 95% CI = 1.50-1.94), and moderate SMC (OR = 1.90, 95% CI = 1.63-2.20) were found to be associated with poor SRH after adjustment for sociodemographic factors and depression in the initial regression model. SMC was found to have partial interaction effects with social capital which was included in the subsequent regression model. Unlike individuals with no SMC and mild SMC, those who reported moderate SMC did not show decreasing probabilities of poor SRH despite increasing levels of social capital. Nevertheless, this analysis suggests that social capital and SMC are independent predictors of poor SRH. Further research needs to be targeted at improving the understanding on how social capital and SMC moderate and interact with the perception of health in older adults.
  11. Yap KH, Azmin S, Che Hamzah J, Ahmad N, van de Warrenburg B, Mohamed Ibrahim N
    J Neurol, 2021 Nov 06.
    PMID: 34743220 DOI: 10.1007/s00415-021-10874-2
    Spinocerebellar ataxias (SCA) comprise a rare, genetic subgroup within the degenerative ataxias and are dominantly inherited, with up to 48 recognized genetic subtypes. While an updated review on the management of degenerative ataxia is published recently, an evidence-based review focussed on the management of SCA is lacking. Here, we reviewed the pharmacological and non-pharmacological management of SCA by conducting a systematic review on Medline Ovid and Scopus. Of 29,284 studies identified, 47 studies (pharmacological: n = 25; non-pharmacological: n = 22) that predominantly involved SCA patients were included. Twenty studies had a high risk of bias based on the Cochrane's Collaboration risk of bias tool. As per the European Federation of Neurological Societies 2004 guideline for therapeutic intervention, the remaining 27 studies were of Class I (n = 4) and Class II (n = 23) evidence. Only two therapies had Level A recommendations for the management of ataxia symptoms: riluzole and immediate in-patient neurorehabilitation. Ten therapies had Level B recommendations for managing ataxia symptoms and require further investigations with better study design. These include high dose valproate acid, branched-chain amino acid, intravenous trehalose; restorative rehabilitation using cycling regimen and videogame; and cerebellar stimulations using transcranial direct current stimulation and transcranial magnetic stimulation. Lithium and coaching on psychological adjustment received Level B recommendation for depressive symptoms and quality of life, respectively. Heterogeneous study designs, different genotypes, and non-standardized clinical measures alongside short duration and small sample sizes may hamper meaningful clinical translation. Therefore, rating of recommendations only serve as points of reference.
  12. Soh YC, Yap KH, McGrattan A, Yasin S, Reidpath D, Siervo M, et al.
    BMJ Open, 2022 Jan 03;12(1):e052175.
    PMID: 34980615 DOI: 10.1136/bmjopen-2021-052175
    INTRODUCTION: Accurate sodium intake estimates in adults with elevated blood pressure are essential for monitoring salt reduction progress and preventing cardiovascular diseases. However, sodium assessments are challenging in this high-risk population because many commonly used antihypertensive drugs alter urinary sodium excretion. Despite the high cost and substantial participant burden of gold-standard 24-hour urine collection, the relative performance of existing spot-urine based equations and dietary self-report instruments have not been well studied in this population, who will benefit from salt restriction. This systematic review aims to describe the current methods of assessing dietary sodium intake in adults with elevated blood pressure and determine what method can provide a valid and accurate estimate of sodium intake compared with the gold standard 24-hour urine collection.

    METHODS AND ANALYSIS: Studies assessing sodium intake in adults aged 18 years and above with reported elevated blood pressure will be included. Five electronic databases (MEDLINE, Embase, Global Health, WoS and Cochrane CENTRAL) will be systematically searched from inception to March 2021. Also, a manual search of bibliographies and grey literature will be conducted. Two reviewers will screen the records independently for eligibility. One reviewer will extract all data, and two others will review the extracted data for accuracy. The methodological quality of included studies will be evaluated based on three scoring systems: (1) National Heart, Lung and Blood Institute for interventional studies; (2) Biomarker-based Cross-sectional Studies for biomarker-based observational studies and (3) European Micronutrient Recommendation Aligned Network of Excellence for validation studies of dietary self-report instruments.

    ETHICS AND DISSEMINATION: As the proposed systematic review will collect and analyse secondary data associated with individuals, there will be no ethical approval requirement. Findings will be disseminated in a peer-reviewed journal or presented at a conference.

    PROSPERO REGISTRATION NUMBER: CRD42020176137.

  13. Yap KH, Azmin S, Makpol S, Damanhuri HA, Mustapha M, Hamzah JC, et al.
    Neural Regen Res, 2023 Jun;18(6):1179-1185.
    PMID: 36453391 DOI: 10.4103/1673-5374.360164
    Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.
  14. Wong ARK, Ng LTE, Lee MH, Yeow JLH, Lim YJ, Yap KH
    Aging Med (Milton), 2024 Aug;7(4):528-534.
    PMID: 39234199 DOI: 10.1002/agm2.12344
    Dementia is characterized by a progressive decline in cognition, behavioral and psychological symptoms (BPSD), and quality of life (QoL). The lack of curative therapies has led to a psychosocial discourse prioritizing QoL of people thriving with dementia (PTD). Group reminiscence therapy (RT) is a relatively inexpensive intervention, with music prompts being a preferred choice, owing to robust musical memory in the early disease stage. However, a synthesis of current evidence is needed to inform research and clinical use of group music RT in dementia care. Therefore, we conducted a systematic review on PubMed, Scopus, CINAHL, APA PsycInfo, and APA PsycArticles to critically appraise published randomized controlled trials examining group music RT to improve cognition, BPSD, and QoL in PTD. Of 14,725 articles, two RCTs involving 102 PTD were included. All studies used prerecorded music for group music RT. All studies were deemed of good quality, adhering to intention-to-treat analysis and assessor blinding. Based on the American Academy of Neurology guidelines, we assigned a Level C recommendation for group music RT for cognition and Level B recommendations for BPSD and QoL (ineffective). In conclusion, group music RT may be useful for symptomatic management in PTD. However, heterogeneous study designs, disease severity, dementia subtype, and outcome measures are likely barriers to meaningful clinical translation. Therefore, the rating of recommendations only serves as a point of reference. Future avenues include live performances as prompts for group music RT.
  15. Mohan D, Yap KH, Reidpath D, Soh YC, McGrattan A, Stephan BCM, et al.
    J Alzheimers Dis, 2020;76(4):1347-1373.
    PMID: 32675410 DOI: 10.3233/JAD-191339
    BACKGROUND: A key focus for dementia risk-reduction is the prevention of socio-demographic, lifestyle, and nutritional risk factors. High sodium intake is associated with hypertension and cardiovascular disease (both are linked to dementia), generating numerous recommendations for salt reduction to improve cardiovascular health.

    OBJECTIVE: This systematic review aimed to assess, in middle- and older-aged people, the relationship between dietary sodium intake and cognitive outcomes including cognitive function, risk of cognitive decline, or dementia.

    METHODS: Six databases (PubMed, EMBASE, CINAHL, Psych info, Web of Science, and Cochrane Library) were searched from inception to 1 March 2020. Data extraction included information on study design, population characteristics, sodium reduction strategy (trials) or assessment of dietary sodium intake (observational studies), measurement of cognitive function or dementia, and summary of main results. Risk-of-bias assessments were performed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tool.

    RESULTS: Fifteen studies met the inclusion criteria including one clinical trial, six cohorts, and eight cross-sectional studies. Studies reported mixed associations between sodium levels and cognition. Results from the only clinical trial showed that a lower sodium intake was associated with improved cognition over six months. In analysis restricted to only high-quality studies, three out of four studies found that higher sodium intake was associated with impaired cognitive function.

    CONCLUSION: There is some evidence that high salt intake is associated with poor cognition. However, findings are mixed, likely due to poor methodological quality, and heterogeneous dietary, analytical, and cognitive assessment methods and design of the studies. Reduced sodium intake may be a potential target for intervention. High quality prospective studies and clinical trials are needed.

  16. Yap KH, Ung WC, Ebenezer EGM, Nordin N, Chin PS, Sugathan S, et al.
    PMID: 28919856 DOI: 10.3389/fnagi.2017.00287
    Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms. Methods: We explored functional near-infrared spectroscopy (fNIRS) alongside a semantic verbal fluency task (SVFT) to investigate any compensation exhibited by the prefrontal cortex (PFC) in Mild Cognitive Impairment (MCI) and mild Alzheimer's disease (AD). In addition, a group of healthy controls (HC) was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD) took part in the present study. Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively); in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively); in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively). The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886) between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE) score] in MCI subjects uniquely. Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment. Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and hypoactivation in mild AD could reflect an inability to compensate. Future studies will investigate the fNIRS parameters with a larger sample size, and their validity as prognostic biomarkers of neurodegeneration.
  17. Yap KH, Azmin S, Abdul Manan H, Yahya N, Ahmad N, Tajurudin FW, et al.
    Parkinsonism Relat Disord, 2024 Jul;124:107013.
    PMID: 38843619 DOI: 10.1016/j.parkreldis.2024.107013
    INTRODUCTION: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients.

    METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo).

    RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated.

    CONCLUSION: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.

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