Subjective cognitive complaints and objective cognitive impairment in patients suspected of obstructive sleep apnea who underwent polysomnography.

OBJECTIVES: Obstructive sleep apnea (OSA) is linked to cognitive impairment. We aimed to investigate subjective cognitive complaints (SCCs) and objective cognitive scores and their relation to polysomnography (PSG) parameters in patients suspected of having OSA. METHODS: A prospective cohort cross-sectional study was conducted at Siriraj Hospital. Patients suspected of OSA who were scheduled for PSG were recruited. Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and Color Trails Test (CTT). The Memory Index Score (MIS) was calculated from the MoCA. Subjective cognitive complaint presence was assessed through direct questioning of patients and by employing the Cognitive Change Index rated by self or informants (CCI-I). Patients with severe dementia were excluded. RESULTS: Among 258 patients (mean age 61.46 ± 7.05 years, 51.2% female), the mean MoCA score was 23.89 ± 3.89. Based on PSG results, patients were categorized into groups as follows: those without OSA or with mild OSA (combined total of 20.1%), moderate OSA (28.3%), or severe OSA (51.6%). Cognitive Change Index rated by self and CCI-I scores correlated significantly (r = 0.238, p = 0.019) but not with the MoCA score or CTT time. Objective cognitive scores were associated with PSG parameters: total sleep time (TST), sleep onset latency, wake after sleep onset, sleep stages, mean O2 saturation, and time spent with SaO2 below 90% (all p < 0.05). Subjective cognitive scores were not associated with PSG parameters, except CCI-I with TST. Participants with objective cognitive impairment had lower education, higher body mass index, more comorbidities, and lower SCC percentage (all p < 0.05). Patients with moderate to severe OSA had a higher proportion of objective cognitive impairment (64.1%) but a lower incidence of SCC (38.3%) than patients with no OSA or mild OSA. Thirty patients with severe OSA and cognitive impairment received continuous positive airway pressure (CPAP) treatment for a mean of 12.2 months. These patients showed MoCA and MIS improvement, but no significant changes were observed in their CTT and Cognitive Change Index scores. CONCLUSIONS: Most patients with OSA had objective cognitive impairment, but SCC was less frequent in patients with more severe OSA. Several PSG parameters correlated with cognitive scores but not with subjective cognitive scores. Patients with severe OSA may benefit cognitively from CPAP treatment.

Clinical presentations and treatment outcomes of Hashimoto encephalopathy at Siriraj Hospital - Thailand's largest national tertiary referral center.

BACKGROUND: Hashimoto encephalopathy has multiple clinical presentations, and other than the presence of thyroid antibody, laboratory and imaging investigations are all non-specific. Data specific to the clinical presentations and treatment outcomes of patients with Hashimoto encephalopathy in Thailand remain scarce. OBJECTIVES: To retrospectively investigate the clinical presentations and treatment outcomes of patients with Hashimoto encephalopathy at Siriraj Hospital. METHODS: Patients who presented with acute encephalopathy at our center during July 2012-March 2017 were evaluated for eligibility. The inclusion criteria were positive anti-thyroperoxidase (anti-TPO) or anti-thyroglobulin (anti-Tg) in serum with negative neuronal antibody in serum or cerebral spinal fluid (CSF). Clinical presentations, symptom duration, laboratory results of thyroid status and thyroid autoantibody, CSF study, and clinical outcomes were collected. RESULTS: Of the 204 patients who presented with encephalopathy, 31 (15.2%) were positive for the anti-TPO or anti-Tg antibody. Of those, 13 patients met the diagnostic criteria for Hashimoto encephalopathy. Clinical presentations included cognitive impairment (76.9%), clouding of consciousness (46.2%), and behavior change (30.8%). The neuropsychiatric presentations were visual hallucination (30.8%), auditory hallucination (15.4%), delusion (7.7%), and mood disturbance (23.1%). Other clinical presentations included seizure (38.5%), abnormal movement (23.1%), sleep disturbance (38.5%), ataxia (46.2%), stroke-like episode (15.4%), and fever (15.4%). Most patients (76.9%) had onset within < 3 months. Regarding outcomes, 1 patient who did not receive corticosteroid died from status epilepticus and septic shock. Among the 12 patients who received corticosteroid, 9 (75%) had marked improvement, 1 (8.3%) had slight improvement, and 2 (16.6%) had no clinical improvement. Seven patients (53.9%) had normal thyroid function, 4 patients (30.8%) had subclinical hypothyroidism, and 2 patients (15.4%) had subclinical hyperthyroidism. CONCLUSIONS: The results of this study revealed cognitive impairment, neuropsychiatric symptoms, seizure, ataxia, and sleep disturbance to be common manifestations of Hashimoto encephalopathy. This condition should always be considered in individuals with subacute onset of unexplained cognitive impairment or cerebellar ataxia. Laboratory and neuroimaging investigations were all found to be nonspecific in Hashimoto encephalopathy. Most patients responded well to treatment, so clinical suspicion and early diagnosis and treatment will lead to improved patient outcomes.

Association study identifies genetic determinants and non-genetic factors on steady-state plasma and therapeutic outcome of galantamine in mixed dementia.

PURPOSE: This study aimed to evaluate the influence of genetic polymorphisms of drug-metabolizing enzyme genes, transporter gene, pathological gene (APOE), and non-genetic factors on therapeutic outcomes as well as steady-state plasma concentrations (Cpss) of galantamine in Thai patients with mixed dementia. METHODS: Fifty-one Thai patients with mixed dementia who received galantamine for at least 6 months were recruited. CYP2D6, CYP3A5, and ABCB1 polymorphisms were detected by TaqMan® Genotyping Assay. UGT1A1 and APOE polymorphism was detected by direct Sanger sequencing technique and restriction fragment length polymorphism technique. Cpss of galantamine was measured by ultra-performance liquid chromatography. Associations of genetic and non-genetic factors with Cpss and clinical outcomes (change in cognitive function as measured by the Thai Mental State Examination (ΔTMSE) scores) were determined by using univariate and multivariate analysis. RESULTS: The multivariate regression model revealed that patients who carried one or more detrimental allelic variant (CYP2D6, CYP3A5, and UGT1A1) showed a tendency toward a higher galantamine adjusted Cpss (B = 34.559, 95% CI = 0.741-68.377, p value = 0.045). Logistic regression analysis also revealed CYP2D6*10 carriers were significantly associated with higher ΔTMSE (B = 5.227, 95% CI = 2.395-8.060, p value = 0.001). UGT1A1 mutant alleles and non-genetic factors including concomitant use of statin drugs and higher education level can attenuate therapeutic outcomes of galantamine. CONCLUSION: Pharmacokinetic-related genes including CYP2D6*10 and UGT1A1 mutant alleles were significantly associated with galantamine adjusted Cpss and cognitive function. Determination of Cpss and genotype could be an adjunct examination to provide further explanation in interindividual variability of galantamine therapeutic outcome.

Quantitative gait analysis in mild cognitive impairment, dementia, and cognitively intact individuals: a cross-sectional case-control study.

BACKGROUND: Cognitive age-related decline is linked to dementia development and gait has been proposed to measure the change in brain function. This study aimed to investigate if spatiotemporal gait variables could be used to differentiate between the three cognitive status groups. METHODS: Ninety-three older adults were screened and classified into three groups; mild cognitive impairment (MCI) (n = 32), dementia (n = 31), and a cognitively intact (n = 30). Spatiotemporal gait variables were assessed under single- and dual-tasks using an objective platform system. Effects of cognitive status and walking task were analyzed using a two-way ANCOVA. Sub-comparisons for between- and within-group were performed by one-way ANCOVA and Paired t-tests. Area Under the Curve (AUC) of Receiver Operating Characteristics (ROC) was used to discriminate between three groups on gait variables. RESULTS: There were significant effects (P < 0.05) of cognitive status during both single and dual-task walking in several variables between the MCI and dementia and between dementia and cognitively intact groups, while no difference was seen between the MCI and cognitively intact groups. A large differentiation effect between the groups was found for step length, stride length, and gait speed during both conditions of walking. CONCLUSIONS: Spatiotemporal gait variables showed discriminative ability between dementia and cognitively intact groups in both single and dual-tasks. This suggests that gait could potentially be used as a clinical differentiation marker for individuals with cognitive problems.

Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer's Disease.

Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and prion diseases have a certain degree of clinical, pathological, and molecular overlapping. Previous studies revealed that many causative mutations in AD, PD, and FTD/ALS genes could be found in clinical familial and sporadic AD. To further elucidate the missing heritability in early-onset Alzheimer's disease (EOAD), we genetically characterized a Thai EOAD cohort by Next-Generation Sequencing (NGS) with a high depth of coverage, capturing variants in 50 previously recognized AD and other related disorders' genes. A novel mutation, APP p.V604M, and the known causative variant, PSEN1 p.E184G, were found in two of the familiar cases. Remarkably, among 61 missense variants were additionally discovered from 21 genes out of 50 genes, six potential mutations including MAPT P513A, LRRK2 p.R1628P, TREM2 p.L211P, and CSF1R (p.P54Q and pL536V) may be considered to be probably/possibly pathogenic and risk factors for other dementia leading to neuronal degeneration. All allele frequencies of the identified missense mutations were compared to 622 control individuals. Our study provides initial evidence that AD and other neurodegenerative diseases may represent shades of the same disease spectrum, and consideration should be given to offer exactly embracing genetic testing to patients diagnosed with EOAD. Our results need to be further confirmed with a larger cohort from this area.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.

Intellectual and physical activities, but not social activities, are associated with better global cognition: a multi-site evaluation of the cognition and lifestyle activity study for seniors in Asia (CLASSA).

BACKGROUND: population ageing will lead to a leap in the dementia population in Asia. However, information about potentials for low-cost and low-risk interventions is limited. OBJECTIVES: to study the associations between lifestyle activities and global cognition from the Cognitive and Lifestyle Activity Study for Seniors in Asia (CLASSA). DESIGN: a cross-sectional study. METHODOLOGY: we studied the association between global cognition and lifestyle activity participation in community living older adults (60 years or over) across nine sites in East Asia. A standardised lifestyle activity questionnaire exploring activities from four categories (intellectual, physical, social and recreational) was used to measure the pattern. Global cognition was categorised by locally validated versions of Mini-mental state examination (MMSE) or Montreal Cognitive Assessment (MoCA) (good cognition, GC-scored at the top 25% among participants with no significant cognitive deficit (SCD); normal cognition, NC-middle 50% among participants with no SCD; mild cognitive deficit, MCD-lowest 25% among participants with no SCD; SCD-below local cut-offs for dementia). RESULTS: two thousand four hundred and four (1,009 men; 1,395 women) participants were recruited. The mean age was 71.0 (7.2) years. A higher variety of intellectual and physical activities were associated with GC; more social activities were associated with higher risks of having impaired cognition (multinomial logistic regression). The same association was found in participants with no SCD and had regular activities for over 10 years (n = 574). CONCLUSION: intellectual activity and physical exercise were associated with better cognitive states in Asian older adults. Community-based intervention may take considerations into specific types of activities to optimise cognition.

The Dementia and Disability Project in Thai Elderly: rational, design, methodology and early results.

BACKGROUND: A strong inverse relationship of functional limitation and socioeconomic status has been established in western ageing society. Functional limitation can be related to chronic diseases, disuse, cognitive decline, and ageing. Among chronic diseases in the Thai population, cerebrovascular diseases, diabetes, and arthritis are common. These factors are known to contribute to disability and poor quality of life in the elder population. Neuropsychiatric problems, cognitive decline, dementia, and cultural issues in elderly people also can alter the quality of life of the elderly. METHODS: The Dementia and Disability Project in Thai Elderly (DDP) aims at comprehensively assessing community dwelling Thai elderly to understand the relationship between disability and motor function, neuropsychiatric symptoms, cognitive function, and chronic diseases. The DDP is the first study to look at the prevalence and etiology of dementia and of mild cognitive impairment (MCI) in Thai elders and to explore the relationship of cognition, disability, small vessel diseases and cortical degeneration with neuroimaging in Thai elderly people. 1998 Thai elders were screened in 2004-2006 and diagnosed as having MCI or dementia. 223 elders with MCI or dementia and cognitively normal elderly had brain magnetic resonance imaging (MRI) or at baseline. 319 elders from the 3 groups had blood tests to investigate the risks and possible etiologies of dementia including genotyping at baseline. RESULTS: The mean age of elders in this study is 69.51(SD=6.71, min=60, max=95) years. 689(34.9%) are men and 1284(65.1%) are women. Mean body weight was 58.36(SD=11.20) kgs. The regression model reveals that performance on gait and balance and serum triglyceride predicts activity of daily living performance (adjusted r2 = 0.280, f=2.644, p=0.003). The majority of abnormal gait in Thai elders was lower level gait disturbance. Only 1.5% (29/1952) had highest level gait disorders. 39.5% of 1964 subjects were free of chronic diseases. Treatment gap (indicating those who have untreated or inadequate treatment) of diabetes mellitus and hypertension in Thai elders in this study was 37% and 55.5% respectively. 62.6% of Thai elders have ApoE3E3 allele. Prevalence of positive ApoE4 gene in this study is 22.85%. 38.6% of Thai elders who had MRI brain study have moderate to severe white matter lesions. CONCLUSION: The large and comprehensive set of measurements in DDP allows a wide-ranging explanation of the functional and clinical features to be investigated in relation to white matter lesions or cortical atrophy of the brain in Thai elderly population. An almost 2 year follow up was made available to those with MCI and dementia and some of the cognitively normal elderly. The longitudinal design will provide great understanding of the possible contributors to disability in the elderly and to the progression of cognitive decline in Thai elders.

Clock drawing test (CDT) and activities of daily living (ADL) questionnaire as a short screening test for dementia in Thai population.

OBJECTIVE: This paper was to develop a short bedside cognitive behavioral test for screening dementia in Thai population. MATERIAL AND METHOD: The 182 elderly subjects were gathered from a community near the vicinity of Siriraj Hospital. Family interview, CDT ADL assessment were assessed by trained nurse. Neurology residents conducted TMSE and Physical examination. The diagnosis of dementia was using the DSM IV criteria. RESULTS: 67 subjects were diagnosed with dementia by DSM IV criteria. The CDT at cut off score of 7 had sensitivity 83.8% and specificity 65.2% with area under ROC being 0.825. For ADL assessment at the cut off score of 5 had sensitivity 74.6% and specificity 79.1% with the area under ROC being 0.849. Using CDT and ADL questionnaires together increased the area under the curve from 0.825 to 0.905. CONCLUSION: The combination of CDT and ADL questionnaire help increase sensitivity and specificity for screening dementia.

Estimated creatinine clearance and cognitive impairment in Thai older adults: a pilot study from the dementia and disability project in Thailand.

BACKGROUND: Chronic kidney disease and dementia are the two common conditions in the older adults. The recent study from the US older adult populations has shown that the lower levels of kidney function are associated with increased prevalence of cognitive impairment. OBJECTIVE: Exploring the relationship between levels of kidney function and cognitive function in Thai community base older adults and finding the threshold of kidney function for which general practitioner should screen for cognitive impairment. MATERIAL AND METHOD: Bangkok community dwelling older adults were recruited during 2004-2006. Serum creatinine and cognitive function were measured. Kidney function was represented in estimated creatinine clearance (eCrCl), calculated by Cockcroft-Gault formula. Cognitive function assessment was evaluated by Mini Mental State Exam Thai version (TMSE). The participants were divided into 4 groups, Model 1, those stratified by level of eCrCl; > or = 90 60-89, 30-59 and < 30 mL/min respectively. Unfortunately, after the authors categorized eCrCl as a Model 1, the number of participants are largely unequally distributed among the 4 groups. Therefore, the authors developed Model 2. In Model 2, eCrCl was divided, by tertile, into 3 groups; eCrCl > 65, 48-65 and < 48 mL/min respectively. Participants with TMSE < 24 were considered to have cognitive impairment. The association between kidney function and cognitive impairment was determined by univariable and multivariable logistic regression models. RESULTS: 317 participants were enrolled, 65.71% (n = 207) were women. The mean age was 71.13 years (SD = 7.99). In Model 1, the authors found a trend which indicated that eCrCl < 30 mL/min increased the prevalence of cognitive impairment when compared with eCrCl > or = 90 mL/min (adjusted odds ratio 3.82; 95% CI 0.90-16.19, p-value = 0.07). In Model 2, the authors also found that populations ofeCrCl < 48 mL/min had a trend to increase the prevalence of cognitive impairment when compared with eCrCl > 65 mL/min (adjusted odds ratio 1.76; 95% CI 0.99-3.12, p-value = 0.052). CONCLUSION: In the present study, the authors could not demonstrate any statistical significant of an association between the lower eCrCl and cognitive impairment. However the authors found that eCrCl < 48 mL/min may have a trend to associate with cognitive impairment. Therefore, the authors may use this eCrCl level for screening prevalence of cognitive impairment in the older adult population.

Assessment of cerebrospinal fluid (CSF) beta-amyloid (1-42), phosphorylated tau (ptau-181) and total Tau protein in patients with Alzheimer's disease (AD) and other dementia at Siriraj Hospital, Thailand.

BACKGROUND: The combination of decreased cerebrospinal fluid (CSF) levels of beta-amyloid (1-42) and increased levels of phosphorylated tau (ptau-181) or total tau protein are known to be biomarkers ofAlzheimer's disease (AD). These biomarkers can also be used as predictors of disease progression in persons with mild cognitive impairment. Utilizing biomarkers to differentiate Alzheimer's disease (AD) against non-Alzheimer dementia (non-AD) needs to be explored. OBJECTIVE: To evaluate the clinical use ofCSF biomarker: beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein for distinguishing Alzheimer's disease (AD) from non-Alzheimer dementia (non-AD) in Thai patients. MATERIAL AND METHOD: Thirty patients diagnosed of dementia during 2005-2007 at Siriraj hospital were offered CSF analysis for beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein. Diagnosis of dementia was performed by a concensus diagnostic group utilizing a standard criteria for diagnosis of AD and other dementia. All CSF testing was performed by Enzyme-Linked Immunoassay (ELISA) technique of the INNOTESTM to analyze these biomarkers. RESULTS: Thirty demented patients were recruited in the study. Fourteen had AD and 16 had non-AD including 5 vascular dementia, 5 normal pressure hydrocephalus, 4 frontotemporal lobar degeneration and others. Mean age of the AD group was 67.79 (12.30) and that of non-AD group was 65.75 (15.04). Twelve AD had decreased levels of CSF /3-amyloid (1-42) (less than 487 pg/ml). Only one patient with AD had increased CSF phosphorylated tau (ptau-181) (more than 61 pg/ml). None of theAD patient had increased CSF total tau (more than 425 pg/ml). Eight patients with non-AD had decreased levels of CSF p-amyloid (1-42), one had increased CSF total tau protein, and none had increased CSF phosphorylated tau (ptau-181) protein. The sensitivity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 85.71%. Those of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 7.14% and 0% consecutively. The specificity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 50%. The specificity of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 100% and 93.75% sequentially. The combination of 2 biomarkers would increase specificity but decrease sensitivity. CONCLUSION: CSF biomarker analysis should be encouraged to use as diagnostic aid in memory clinic especially to help diagnosis of atypical presentation of AD. The usefulness of longitudinal data needs to be explored.

Accuracy of Support-Vector Machines for Diagnosis of Alzheimer's Disease, Using Volume of Brain Obtained by Structural MRI at Siriraj Hospital.

Background: The determination of brain volumes using visual ratings is associated with an inherently low accuracy for the diagnosis of Alzheimer's disease (AD). A support-vector machine (SVM) is one of the machine learning techniques, which may be utilized as a classifier for various classification problems. This study exploratorily investigated the accuracy of SVM classification models for AD subjects using brain volume and various clinical data as features. Methods: The study was designed as a retrospective chart review. A total of 201 eligible subjects were recruited from the Memory Clinic at Siriraj Hospital, Thailand. Eighteen cases were excluded due to incomplete MRI data. Subjects were randomly assigned to a training group (AD = 46, normal = 46) and testing group (AD = 45, normal = 46) for SVM modeling and validation, respectively. The results in terms of accuracy and a receiver operating characteristic curve analysis are reported. Results: The highest accuracy for brain volumetry (62.64%) was found using the hippocampus as a single feature. A combination of clinical parameters as features provided accuracy ranging between 83 and 90%. However, a combination of brain volumetry and clinical parameters as features to the SVM models did not improve the accuracy of the result. Conclusions: In our study, the use of brain volumetry as SVM features provided low classification accuracy with the highest accuracy of 62.64% using the hippocampus volume alone. In contrast, the use of clinical parameters [Thai mental state examination score, controlled oral word association tests (animals; and letters K, S, and P), learning memory, clock-drawing test, and construction-praxis] as features for SVM models provided good accuracy between 83 and 90%.

Strategies for the use of Ginkgo biloba extract, EGb 761® , in the treatment and management of mild cognitive impairment in Asia: Expert consensus.

BACKGROUND: Mild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761® , is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits. AIMS: To present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761® in MCI. MATERIALS & METHODS: The ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761® as a treatment option. RESULTS: EGb 761® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761® may help delay progression from MCI to dementia in some individuals. DISCUSSION: EGb 761® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761® may benefit MCI patients with underlying CVD. CONCLUSION: As an expert group, we suggest it is clinically appropriate to incorporate EGb 761® as part of the multidomain intervention for MCI.

High burden of cerebral white matter lesion in 9 Asian cities.

Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer's disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

Priorities for research consortia on Alzheimer's disease.

Coordination and harmonization of efforts between five major research consortia on Alzheimer's disease may increase our understanding of this condition and improve our therapeutic approaches. Specific opportunities include a registry for families with early onset dementia, a study registry, minimal data sets, validation of assessment tools and outcomes, update on ethical issues, resolution of methodological issues, new investigators training, longitudinal observation studies, prevention studies, and liaison with stakeholders such as Alzheimer Disease International.

Action observation combined with gait training to improve gait and cognition in elderly with mild cognitive impairment A randomized controlled trial.

Owing to advancement of medical technology and current knowledge, the population has a longer life expectancy, leading to an increase in the proportion of elderly. OBJECTIVE: The study aimed to investigate the effect of action observation (AO) combined with gait training on gait and cognition in elderly with mild cognitive impairment (MCI). METHODS: Thirty-three participants were randomly allocated to action observation with gait training (AOGT), gait training (GT), and control (CT) groups. The AOGT and GT groups received a program of observation and gait training protocol with the same total duration of 65 min for 12 sessions. For the observation, the AGOT group watched a video of normal gait movement, while the GT group watched an abstract picture and the CT group received no training program. All participants were assessed for gait parameters during single- and dual-tasks using an electronic gait mat system and were assessed for cognitive level using the Montreal Cognitive Assessment (MoCA) at baseline, after training and at 1-month follow-up. RESULTS: The results showed that the AOGT group had significant improvements in gait speeds during single- and dual-tasks, as well as better MoCA score, while the GT group had significant improvement only in gait speed. CONCLUSION: The adjunct treatment of AO with gait training provides greater benefits for both gait and cognitive performances in elderly with MCI.

Com o avanço da tecnologia médica e do conhecimento atual, a população tem uma expectativa de vida mais longa, levando a um aumento na proporção de idosos. OBJETIVO: O estudo teve como objetivo investigar o efeito da observação de ação (AO) combinada com o treinamento da marcha na marcha e cognição em idosos com comprometimento cognitivo leve (CCL). MÉTODOS: Trinta e três participantes foram alocados aleatoriamente para observação de ação com grupos de treinamento de marcha (AOGT), treinamento de marcha (GT) e controle (CT). Os grupos AOGT e GT receberam um programa de observação e protocolo de treinamento de marcha com a mesma duração total de 65 minutos por 12 sessões. Na observação, o grupo AGOT assistiu a um vídeo de movimento normal da marcha, enquanto o grupo GT assistiu a uma figura abstrata e o grupo CT não recebeu nenhum programa de treinamento. Todos os participantes foram avaliados quanto aos parâmetros da marcha durante tarefas simples e duplas, utilizando um sistema eletrônico de esteira da marcha e avaliados quanto ao nível cognitivo, utilizando a Avaliação Cognitiva de Montreal (MoCA) na linha de base, após o treinamento e 1 mês de acompanhamento. RESULTADOS: Os resultados mostraram que o grupo AOGT apresentou melhorias significativas nas velocidades da marcha durante tarefas simples e duplas, além do escore MoCA, enquanto o grupo GT teve melhora significativa apenas na velocidade da marcha. CONCLUSÃO: O tratamento adjunto da AO com o treinamento da marcha proporciona maiores benefícios tanto do desempenho da marcha quanto do desempenho cognitivo em idosos com CCL.

Pathogenic PSEN1 Glu184Gly Mutation in a Family from Thailand with Probable Autosomal Dominant Early Onset Alzheimer's Disease.

A pathogenic mutation in PSEN1 p.Glu184Gly was discovered in a Thai family with early onset Alzheimer's disease (EOAD) as the first case in Asia. Proband patient presented memory impairment and anxiety at the age of 41 years. Family history was positive, since several family members were also diagnosed with dementia (father and grandfather). MRI in the patient revealed global cortical atrophy without specific lesions or lacuna infarctions. Extensive genetic profiling for 50 neurodegenerative disease related genes was performed by next generation sequencing (NGS) on the patient. PSEN1 Glu184Gly was previously reported in French families with frontal variant Alzheimer's disease (AD). Interestingly, this mutation is located near the splicing site and could possibly result in abnormal cleavage of PSEN1 transcript. Furthermore, 3D models from protein structural predictions revealed significant structural changes, since glycine may result in increased flexibility of TM-III helix. Inter/intra-helical interactions could also be altered. In the future, functional studies should be performed to verify the probable role PSEN1 Glu184Gly in amyloid beta processing and pathogenicity.

Role of Fluid Biomarkers and PET Imaging in Early Diagnosis and its Clinical Implication in the Management of Alzheimer's Disease.

Clinical diagnosis of Alzheimer's disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-ß 42 (Aß42) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (Aß42 and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in technology that uses approved radioactive diagnostic agents (florbetapir, flutemetamol, or florbetaben) to estimate Aß neuritic plaque density in adults with cognitive impairment evaluated for AD and other causes of cognitive decline. There is no cure for AD to date-the disease progression cannot be stopped or reversed; approved pharmacological agents (donepezil, galantamine, and rivastigmine; memantine) provide symptomatic treatment. However, the disease-modifying therapies are promising; aducanumab and CAD106 are in phase III trials for the early stages of AD. In conclusion, core CSF biomarkers reflect pathophysiology of AD in the early and late stages; the application of approved radiotracers have potential in amyloid-PET brain imaging to detect early AD.

Safety and tolerability of galantamine in possible Alzheimer's disease with or without cerebrovascular disease and vascular dementia in Thai patients.

The purpose of this study was to explore factors that influence the clinical safety and tolerability associated with galantamine administration in Thai Alzheimer's disease patients with or without cerebrovascular disease and vascular dementia. This was an analysis of previous study. Tolerability and safety profile were analyzed according to sex, age, body weight, Thai mental state examination (TMSE) score, Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) score, and Alzheimer's disease cooperative study/activities of daily living (ADCS/ADL) score. The most common adverse events were nausea, dizziness, and weight loss which more often occurred during the dose-escalation phase. Mean body weight lost at week 24 was 0.9 kg. Sex, age, body weight, and ADAS-cog score did not influence the incidence of any adverse events. Dizziness was more likely to occur in patients with low TMSE and high ADCS/ADL score (p = 0.02 and p = 0.050, respectively). Patients with TMSE score equal or higher than 23 more often experienced muscle cramps and fatigue than who had TMSE lower 23 (p < 0.05). However, flexible dose escalation of galantamine with a 4-week schedule was safe and well tolerated in Thai AD patients.