Investigating Neurocognitive Disorders Epidemiology

King Chulalongkorn Memorial Hospital990 enrolled

Overview

This is a prospective cohort study with the main purpose of predicting progression neurocognitive disorders in Thai population. The main predictor variables to be evaluated are plasma phosphorylated tau (p-tau) level and cognitive test scores, which will be combined using statistical/computational modeling. Additionally, it seeks to evaluate biomarkers for diagnosing disease pathologies, understand their correlation with clinical outcomes, and explore the socioeconomic impact of neurocognitive disorders. The study invites both participants for biospecimen collection, structured interviews, and cognitive examinations and schedules follow-up visits annually or biennially.

The INDE study is a prospective cohort aimed at investigating the natural history and epidemiology of neurocognitive disorders in Thailand. Its primary objective is to develop a predictive model that combines biomarkers (eg. plasma phosphorylated tau) and cognitive performance to accurately predict cognitive decline. Additional objectives include cross-sectional evaluation of various biomarkers for diagnosing disease pathologies, identifying correlations between biomarkers and clinical outcomes, understanding the impact of receiving a biological diagnosis, describing the epidemiology of neurocognitive disorders including risk factors and social determinants of health (SDH), exploring the socioeconomic consequences of these disorders, and establishing a biorepository for future research. The study invites both healthy volunteers and patients referred from memory clinics to participate in a 4-hour visit during which various research procedures are conducted: collection of biospecimens (blood, saliva, sweat), structured interviews covering symptoms, comorbidities, risk factors, SDH, and quality of life, as well as a comprehensive cognitive examination. Participants are scheduled for annual or biennial follow-up visits based on their cognitive status. For those consenting to specific disclosures, investigators provide some biomarker test results and offer post-test counseling based on available research literature. Depending on current funding, a subset of participants meeting additional criteria may also undergo evaluation using appropriate neuroimaging or cerebrospinal fluid (CSF) biomarkers.

Study Type

OBSERVATIONAL

Enrollment

990

Interventions

Plasma tau phosphorylated at Thr217DIAGNOSTIC_TEST

Plasma concentration of tau protein phosphorylated at Thr217 as measured on the Meso Scale Discovery, single molecule array (Simoa) or the in-house mass spectrometry platform.

Neurocognitive examinationOTHER

Traditional (paper and pencil) neurocognitive/neuropsychiatric examination performed by certified psychologists. This includes: Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), Wechsler Memory Scale - Fourth Edition (WMS-IV), Neuropsychiatric Inventory - Questionnaire (NPI-Q), Thai Geriatric Depression Scale (TGDS), General Anxiety Disorder - 7 (GAD-7), The Barthel activities of daily living (ADL) Index, Chula ADL Index.

Eligibility

Sex: ALLMin age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

1. Cognitively Healthy Individuals INCLUSION CRITERIA * Demonstrate normal cognitive function within the expected range on objective cognitive tests. * Proficient in speaking and understanding Thai without the need for a translator to participate. EXCLUSION CRITERIA * Significant neurological or uncontrolled psychiatric illness. * Significant unstable systemic condition or end-stage organ failure that affects study participation. 2. Mild Cognitive Impairment INCLUSION CRITERIA * Display impaired/abnormal performance on objective cognitive tests. * Does not meet criteria for dementia per NIA-AA (or major neurocognitive disorder per DSM-5). * Proficient in speaking and understanding Thai without the need for a translator to participate. EXCLUSION CRITERIA * Significant neurological or uncontrolled psychiatric illness. * Significant unstable systemic condition or end-stage organ failure that affects study participation. 3. Late Onset Dementia INCLUSION CRITERIA * Display impaired/abnormal performance on objective cognitive tests. * Meets criteria for dementia per NIA-AA (or major neurocognitive disorder per DSM-5), including dementia due to Alzheimer's disease or other causes. * Begins to experience symptoms, identified by the physician as a part of dementia continuum, occurring after the age of 65. * Proficient in speaking and understanding Thai without the need for a translator to participate. EXCLUSION CRITERIA * Significant neurological or uncontrolled psychiatric illness. * Significant unstable systemic condition or end-stage organ failure that affects study participation. 4. Early Onset Dementia INCLUSION CRITERIA * Display impaired/abnormal performance on objective cognitive tests. * Meets criteria for dementia per NIA-AA (or major neurocognitive disorder per DSM-5), including dementia due to Alzheimer's disease or other causes. * Begins to experience symptoms, identified by the physician as a part of dementia continuum, occurring before the age of 65. * Proficient in speaking and understanding Thai without the need for a translator to participate. EXCLUSION CRITERIA * Significant neurological or uncontrolled psychiatric illness. * Significant unstable systemic condition or end-stage organ failure that affects study participation.

Outcomes

Primary Outcomes

Progression to dementia

Fulfilling the criteria for dementia according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) 2018 criteria or major neurocognitive disorder (according to DSM-5) as evaluated by neurologist with special interests in neurocognitive disorders. If such designation is not available, reaching a global CDR score of 1 will be used as a substitute. This outcome only applies to cognitively healthy and mild cognitive impairment cohort.

Time frame: At 2, 4, 6 and 8 years

Changes in Sum of Boxes of the Clinical Dementia Rating Scale

Administered by a certified psychologist in accordance with Morris, J.C. (1993). Minimum value: 0 Maximum value: 18 Higher scores mean a worse outcome.

Time frame: At 2, 4, 6 and 8 years

Secondary Outcomes

Changes in the Montreal Cognitive Assessment

Administered by a certified psychologist. Minimum value: 0 Maximum value: 30 Higher scores mean a better outcome.

Time frame: At 2, 4, 6 and 8 years

Changes in the Montreal Cognitive Assessment - Memory Index Score

Administered by a certified psychologist. Minimum value: 0 Maximum value: 15 Higher scores mean a better outcome.

Time frame: At 2, 4, 6 and 8 years

Changes in the Mini Mental State Examination

Administered by a certified psychologist. Minimum value: 0 Maximum value: 30 Higher scores mean a better outcome.

Time frame: At 2, 4, 6 and 8 years

Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Visual Reproduction Scaled Score

Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome.

Time frame: At 2, 4, 6 and 8 years

Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory Scaled Score

Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome.

Time frame: At 2, 4, 6 and 8 years

Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Verbal Paired Associates Scaled Score

Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome.

Time frame: At 2, 4, 6 and 8 years

Biological diagnosis of Alzheimer's disease

Receiving the diagnosis of Alzheimer's disease based on the abnormality of any pathology-specific biomarkers that fulfills the current NIA-AA criteria. These biomarkers include, but not limited to, amyloid positron emission tomography (PET) (eg. \[18 F\]-Florbetaben PET), tau-PET (eg. \[18F\]PI-2620 PET), or CSF levels of core Alzheimer's disease biomarkers.

Time frame: within 6 months of baseline measurement

Biological staging of Alzheimer's disease

Staging of Alzheimer's disease based on the abnormality of pathology-specific biomarkers according to the current NIA-AA criteria.

Time frame: within 6 months of baseline measurement

Quantitative amyloid PET uptake.

Amyloid PET uptake tracer uptake quantified in Centiloids.

Time frame: within 6 months of baseline measurement

Quantitative tau PET uptake in various cortical regions.

Cortical tau-PET uptake measured using mean standardized uptake value ratios of referenced against inferior cerebellar cortex. The pre-specified regions of interest are analogous with Braak staging (as suggested by Cho, H. (2016).): Stage I-II, entorhinal cortex; Stage III, parahippocampal and fusiform cortices, and amygdala; Stage IV, inferior and middle temporal cortices; Stage V, inferior parietal, posterior cingulate, lingual, orbitofrontal, insular, supramarginal, lateral occipital, superior temporal, precuneus, superior parietal, superior, middle, and inferior frontal, and anterior cingulate cortices; Stage VI, medial occipital, precentral, paracentral, and postcentral cortices.

Time frame: within 6 months of baseline measurement

Future diagnosis of Alzheimer's disease dementia.

All of the following: 1. Fulfilling the criteria for dementia (NIA-AA 2018) or major neurocognitive disorder (DSM-5) as evaluated by neurologist with special interests in neurocognitive disorders. If such designation is not available, reaching a global CDR score of 1 will be used as a substitute. 2. Receiving the diagnosis of Alzheimer's disease based on the abnormality of any pathology-specific biomarkers that fulfills the current NIA-AA criteria. These biomarkers include, but not limited to, amyloid-PET (eg. \[18 F\]-Florbetaben PET), tau-PET (eg. \[18F\]PI-2620 PET), or CSF levels of core Alzheimer's disease biomarkers. 3. Conclusion made by a neurologist with special interests in neurocognitive disorders that dementia is predominately due to Alzheimer's disease.

Time frame: At 2, 4, 6 and 8 years

Investigating Neurocognitive Disorders Epidemiology

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts