The Bayesian approach for real­world implementation of plasma p­tau217 in tertiary care memory clinics in Thailand.

INTRODUCTION: Plasma phosphorylated tau (p-tau)217 is a promising biomarker for Alzheimer's disease (AD) diagnosis, but its clinical implementation remains challenging. We propose a strategy based on Bayes' theorem and test it in real-life memory clinics. METHODS: Memory clinic patients were evaluated by neurocognitive specialists for prespecified diagnosis and subsequently underwent blood collection for p-tau217, cerebrospinal fluid, or amyloid positron emission tomography. Using cross-validation, the Bayesian approach (pretest probability × individualized likelihood ratio) was compared to other models for AD diagnosis. RESULTS: The Bayesian strategy demonstrated an area under the receiver operating characteristic curve (AUC) of 0.98 (95% confidence interval [CI]: 0.96-1.0), significantly outperforming multivariable logistic regression (p-tau217, age, apolipoprotein E; AUC 0.95, p = 0.024) and p-tau217 alone (AUC = 0.94, p = 0.007). When applying the two-threshold approach, the Bayesian strategy yielded an accuracy of 0.94 (95% CI: 0.88-1.0) without requiring confirmatory tests in 62.9% of the iterations. DISCUSSION: The Bayesian strategy offers an effective and flexible approach to address the limitations of plasma p-tau217 in clinical practice. HIGHLIGHTS: Incorporating pretest probability into the interpretation of plasma phosphorylated tau (p-tau)217 improves the diagnostic performance significantly. The strategy could obviate the need for confirmatory testing in most of the patients. Plasma p-tau217 proves useful as a biomarker for Alzheimer's disease in low- and middle-income country such as Thailand.

Cognitive impairments predict the behavioral and psychological symptoms of dementia.

Introduction: The purpose of this study was to (1) validate the Thai version of the Neuropsychiatric Inventory Questionnaire (NPI-Q) as a screening tool for behavioral and psychological symptoms of dementia (BPSD), and (2) examine the relationship between cognitive performance and BPSD in an elderly population with amnestic mild cognitive impairment (aMCI) and dementia of Alzheimer's type (DAT). Methods: One hundred and twenty participants, comprising 80 aMCI and 40 DAT patients, and their respective caregivers were included in the study. Participants completed the NPI-Q and the Neuropsychiatric Inventory (NPI) within 2 weeks of each other and cognitive performance was primarily assessed using the Montreal Cognitive Assessment (MoCA). Results: The Thai NPI-Q had good validity and reliability. Pure exploratory bifactor analysis revealed that a general factor and a single-group factor (with high loadings on delusions, hallucinations, apathy, and appetite) underpinned the NPI-Q domains. Significant negative correlations between the MoCA total score and the general and single-group NPI-Q scores were found in all subjects (aMCI + DAT combined) and DAT alone, but not in aMCI. Cluster analysis allocated subjects with BPSD (10% of aMCI and 50% of DAT participants) into a distinct "DAT + BPSD" class. Conclusion: The NPI-Q is an appropriate instrument for assessing BPSD and the total score is largely predicted by cognitive deficits. It is plausible that aMCI subjects with severe NPI-Q symptoms (10% of our sample) may have a poorer prognosis and constitute a subgroup of aMCI patients who will likely convert into probable dementia.

Prospective evaluation of plasma phosphorylated tau in a real-life memory clinic in Thailand.

INTRODUCTION: Despite the substantial accuracy of plasma p-tau in diagnosing Alzheimer's disease (AD) in research cohorts, data on real-life memory clinic patients are lacking. METHODS: Memory clinic patients at their early symptomatic stages were prospectively enrolled to undergo routine clinical assessment, plasma p-tau181 quantification (Simoa), amyloid and tau-positron emission tomography (PET). The diagnostic performance of plasma p-tau181, neurocognitive specialists, and regional tau-PET were compared head-to-head using amyloid-PET as the reference standard. RESULTS: Plasma p-tau181 has the area under the curve (AUC), sensitivity, specificity, and accuracy of 0.84 (95% confidence interval [CI] 0.73-0.94), 0.80 (95% CI 0.64-0.90), 0.75 (95% CI 0.51-0.90), and 0.78 (95% CI 0.65-0.88) for detecting amyloid-PET positivity in early symptomatic patients, respectively. The AUC of clinical diagnosis and tau-PET were 0.70 (95% CI 0.56-0.85) and 0.88 (95% CI 0.79-0.97), respectively. DISCUSSION: Plasma p-tau181 also performed well in real-life memory clinic settings and its role in clinical practice is supported.

Use of the Montreal Cognitive Assessment Thai Version to Discriminate Amnestic Mild Cognitive Impairment from Alzheimer's Disease and Healthy Controls: Machine Learning Results.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is an effective and applicable screening instrument to confirm the diagnosis of amnestic mild cognitive impairment (aMCI) from patients with Alzheimer's disease (AD) and healthy controls (HCs). OBJECTIVES: This study aimed to determine the reliability and validity of the following: (a) Thai translation of the MoCA (MoCA-Thai) and (b) delineate the key features of aMCI based on the MoCA subdomains. METHODS: This study included 60 HCs, 61 aMCI patients, and 60 AD patients. The MoCA-Thai shows adequate psychometric properties including internal consistency, concurrent validity, test-retest validity, and inter-rater reliability. RESULTS: The MoCA-Thai may be employed as a diagnostic criterion to make the diagnosis of aMCI, whereby aMCI patients are discriminated from HC with an area under the receiver-operating characteristic (AUC-ROC) curve of 0.813 and from AD patients with an AUC-ROC curve of 0.938. The best cutoff scores of the MoCA-Thai to discriminate aMCI from HC is ≤24 and from AD > 16. Neural network analysis showed that (a) aberrations in recall was the most important feature of aMCI versus HC with impairments in language and orientation being the second and third most important features and (b) aberrations in visuospatial skills and executive functions were the most important features of AD versus aMCI and that impairments in recall, language, and orientation but not attention, concentration, and working memory, further discriminated AD from aMCI. CONCLUSIONS: The MoCA-Thai is an appropriate cognitive assessment tool to be used in the Thai population for the diagnosis of aMCI and AD.

Pattern of cortical thinning in logopenic progressive aphasia patients in Thailand.

BACKGROUND: Logopenic progressive aphasia (LPA) is an uncommon neurodegenerative disorder primarily characterized by word-finding difficulties and sentence repetition impairment. Prominent cortical atrophy around left temporo-parietal junction (TPJ) is a classical imaging feature of LPA. This study investigated cortical thinning pattern in clinically diagnosed LPA patients using non-demented subjects as a control group. We also aimed to explore whether there was prominent thinning of other cortical area additional to the well-recognized left TPJ. METHODS: Thicknesses of all cortical regions were measured from brain magnetic resonance images using an automated command on Freesurfer software. Cortical thickness of the LPA and control groups were compared by two methods: 1) using a general linear model (GLM) in SPSS software; and 2) using a vertex-by-vertex GLM, performed with Freesurfer's QDEC interface. RESULTS: Besides the well-recognized left TPJ, cortical regions that were significantly thinner in the LPA group by both comparison methods included left caudal middle frontal gyrus (CMFG) (p = 0.006 by SPSS, p = 0.0003 by QDEC), left rostral middle frontal gyrus (p = 0.001 by SPSS, p = 0.0001 by QDEC), left parahippocampal gyrus (p = 0.008 by SPSS, p = 0.005 by QDEC) and right CMFG (p = 0.005 by SPSS, p = 0.0001 by QDEC). CONCLUSIONS: Our results demonstrated that thinning of middle frontal gyri may be an additional feature in clinically diagnosed LPA patients. Involvement of left parahippocampal gyrus may reflect the underlying neuropathology of Alzheimer's disease in majority of the LPA patients.

Associations between hypoxia parameters in obstructive sleep apnea and cognition, cortical thickness, and white matter integrity in middle-aged and older adults.

OBJECTIVE: This study aimed to investigate the association between each parameter of intermittent hypoxia in obstructive sleep apnea (OSA) and the cognitive profile, cortical thickness, and white matter integrity in middle-aged and older adults. METHODOLOGY: Participants were newly diagnosed with moderate or severe OSA from the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Respiratory parameters from polysomnography were extracted. Each participant was tested on a battery of neuropsychological tests and underwent an MRI scan of the brain. Cortical thickness analysis and diffusion tensor imaging analysis were performed. Participants were classified as having either severe or mild hypoxia based on parameters of hypoxia, i.e., oxygen desaturation index, lowest oxygen saturation, and the percentage of total sleep time spent below 90% oxygen saturation. RESULTS: Of 17 patients with OSA, there were 8 men (47%). Median age was 57 years and median AHI was 60.6. Comparison of cortical thickness between the severe and the mild group of each hypoxic parameter revealed two clusters of cortical thinning at the right inferior frontal gyrus (p-value = 0.008) and right inferior parietal gyrus (p-value = 0.006) in the severe desaturation group and a cluster of cortical thinning at the superior parietal gyrus (p-value = 0.008) in the high oxygen desaturation index group. There was no difference in cognitive function or white matter integrity between groups. CONCLUSIONS: The magnitude of the degree and frequency of desaturations in OSA are associated with a decrease in cortical thickness at the frontal and parietal regions.

Diffusion tensor imaging in Alzheimer's disease and affective disorders.

The functional organization of the brain in segregated neuronal networks has become a leading paradigm in the study of brain diseases. Diffusion tensor imaging (DTI) allows testing the validity and clinical utility of this paradigm on the structural connectivity level. DTI in Alzheimer's disease (AD) suggests a selective impairment of intracortical projecting fiber tracts underlying the functional disorganization of neuronal networks supporting memory and other cognitive functions. These findings have already been tested for their utility as clinical markers of AD in large multicenter studies. Affective disorders, including major depressive disorder (MDD) and bipolar disorder (BP), show a high comorbidity with AD in geriatric populations and may even have a pathogenetic overlap with AD. DTI studies in MDD and BP are still limited to small-scale monocenter studies, revealing subtle abnormalities in cortico-subcortial networks associated with affect regulation and reward/aversion control. The clinical utility of these findings remains to be further explored. The present paper presents the methodological background of diffusion imaging, including DTI and diffusion spectrum imaging, and discusses key findings in AD and affective disorders. The results of our review strongly point toward the necessity of large-scale multicenter multimodal transnosological networks to study the structural and functional basis of neuronal disconnection underlying different neuropsychiatric diseases.

Diffusion tensor imaging to determine effects of antidementive treatment on cerebral structural connectivity in Alzheimer's disease.

Introduction of diffusion tensor imaging (DTI) in 1980 and its advancement in the last three decades offered the possibility to visualize and quantify changes in white matter. DTI allows the evaluation of the structural integrity in complex neurodegenerative diseases, such as Alzheimer's disease (AD). Progressive disintegration of functional and structural neural network coordination contributes to the cognitive dysfunction in AD. Therefore, detection of loss of cortico-cortical projections may support an early diagnosis at prodromal stages of disease which may prove essential for future preventive AD treatment trials. Moreover, structural integrity measured by DTI may help to distinguish between symptomatic and disease modifying effects of pharmacological interventions. This review gives a concise account on the physical basis of DTI acquisition and processing. We summarize DTI findings in normal aging and AD and regarding the effects of cognitive intervention and antidementive treatment on structural neural connectivity. Finally, we evaluate the promising future potential of DTI to become a surrogate endpoint in clinical AD trials.

Isolated motor neglect following infarction of the posterior limb of the right internal capsule: a case study with diffusion tensor imaging-based tractography.

Motor neglect is an impairment in the ability to initiate movement not attributable to muscle weakness. The neural network of this syndrome is not precisely defined. We present the diffusion tensor imaging (DTI)-base tractography findings in an acute stroke patient presenting with isolated motor neglect following infarction in the posterior limb of the internal capsule within the anterior choroidal artery territory. A left-handed 17-year-old woman presented with an acute onset of motor neglect of her left arm. Motor tasks performed with the affected limb were awkward; however, the tasks could be accomplished with effort. Magnetic resonance imaging (MRI) including DTI of the brain were performed. DTI-based tractography extracted the fiber tracts originating from regions of interest placed on the ischemic lesion. MRI revealed an acute ischemic infarction at the posterior part of the posterior limb of the right internal capsule within the territory of the anterior choroidal artery. DTI-based tractography showed fiber tracts projecting from the lesion to the posterior part of the supplementary motor area and some fiber tracts projecting to posterior aspects of the thalamus. DTI-based tractography may be a useful tool for visualizing white matter pathways in vivo following an acute infarction. Our case study supports the notion that fiber tracts connecting the posterior part of the posterior limb of the internal capsule, supplementary motor area, and posterior aspect of the thalamus are key areas of a neural network involved in motor neglect syndrome.

Vasoreactivity induced by acetazolamide in patients with vascular dementia versus Alzheimer's disease.

UNLABELLED: Acetazolamide vasoreactive test measures the increment of cerebral blood flow caused by compensatory vasodilatation ability of cerebral vessels which can be detected by transcranial Doppler ultrasound (TCD). This study aimed to compare the vascular reactivity in patients with vascular dementia (VaD) and Alzheimer's disease (AD). PATIENTS AND METHODS: AD and VaD patients were recruited from the King Chulalongkorn Hospital Dementia Clinic. Thai Mini-mental State Examination was used for dementia detection. AD and possible VaD were defined by NINCDS/ADRDA and NINDS-AIREN criteria. Patients with extracranial carotid artery stenosis >50% and intracranial artery stenosis were excluded. TCD examination was performed using DWL Multi Dop-T. TCD was performed on MCA with insonation depth between 45 and 60 mm. Baseline end diastolic velocity (EDV), mid systolic velocity (MSV) and peak systolic velocity (PSV) were recorded. The velocities were obtained at 2, 5, 10 and 20 min after acetazolamide (1000 mg) injection. Mean baseline velocities (Vo) and velocities after acetazolamide injection (Va) were compared. Percentage of mean increment velocities was calculated {[(Va-Vo)/Vo]x100%}. Percentage differences of mean velocity change from Vo to Va at each recorded minute were compared. SPSS for Windows version 11.5.0. was used. RESULT: Nine AD (5 males) and 9 VaD (6 males) were selected. Average ages of VaD and AD groups were 66.11 years-old and 75.22 years-old respectively. Mini-mental State Examination (MMSE) score in VaD and AD were 21.13 and 19.00. Mean baseline EDV and MSV in VaD were higher than AD but mean PSV was lower. The percentage of velocity change after acetazolamide in AD was higher than VaD at 5, 10 and 20 min. However the differences were not statistically significant. CONCLUSION: Acetazolamide vasoreactive test using TCD may be the additional criterion to differentiate VaD from AD. Further study with more number of subjects for the study or higher dose of acetazolamide may be needed to reveal the significant difference of vasoreactive response between VaD and AD patients.

Thrombolytic therapy in acute ischemic stroke in Asia: The first prospective evaluation.

OBJECTIVE: Intravenous thrombolytic therapy has been widely recommended as a standard treatment for acute ischemic stroke in most clinical practice guidelines. However, the experience in Asia is still limited. We report the first prospective case series of thrombolytic therapy in a developing Asian country. PATIENTS AND METHODS: Consecutive patients with acute ischemic stroke who presented within 3 h of onset were screened under stroke fast track program. Those who were eligible were treated with intravenous recombinant tissue plasminogen activator (rt-PA). General and neurological examinations together with the National Institute of Health stroke scale (NHISS) and modified Rankin scale (MRS) were recorded prior to and after the treatment at 1 h, 24 h, on discharge and at 3 months. Hemorrhagic brain lesion and death within 3 months were also recorded. RESULTS: Thirty-four patients or 2.1% of patients with acute stroke received intravenous thrombolysis. The mean pretreatment NIHSS was 18.8 and the majority of patients had stroke in the middle cerebral artery territory. The mean door-to-needle time was 72.6 min (ranged 20-150 min). Major neurological improvement, defined as improving of the NIHSS >8 points or NIHSS of 0 points at 24 h, was observed in 17 patients (50%). Intracerebral hemorrhage was detected in four cases (11.8%), two of them were symptomatic (5.9%) and one was fatal. CONCLUSION: Intravenous thrombolysis can be given in patients with acute stroke in our population. Our cases were more severe than other studies. However, half of them experienced major neurological improvement. The risk of hemorrhagic brain lesion is not much higher than previously reported.