Investigating Neurocognitive Disorders Epidemiology (INDE)

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.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Alzheimer Disease; Cognitive Decline
• Intervention / Treatment: Diagnostic test: Plasma tau phosphorylated at Thr217; Other: Neurocognitive examination

Detailed Description

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 (Estimated): 990

Contacts and Locations

• Study Contact: Name: Poosanu Thanapornsangsuth, M.D.; Phone Number: 3561 +66 (0)2 2564000; Email: poosanu.t@chula.ac.th
• Study Contact Backup: Name: Thanakit Pongpitakmetha, M.D.; Email: thanakit.p@chula.ac.th

Study Locations

• Thailand
  • Bangkok
    • Pathum Wan, Bangkok, Thailand, 10330
      • Recruiting
      • King Chulalongkorn Memorial Hospital
      • Contact: Adipa Chongsuksantikul, D.Eng.; Phone Number: +66 (0)84 1134443; Email: adipar@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The target population of this study comprises individuals with a risk of cognitive decline in Thailand categorized by their cognitive status.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitively healthy; This cohort includes participants with or without subjective complaints whose results of cognitive examination are normal. Participants will undergo clinical, epidemiological, and cognitive assessments, as well as biospecimen collection every two years, over an 8-year follow-up period.	Diagnostic test: Plasma tau phosphorylated at Thr217; 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.; Other Names: S-PLEX Human Tau (pT217) Kit; ALZpath pTau-217 CARe Advantage Kit; Other: Neurocognitive examination; 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.
Mild cognitive impairment; This cohort includes participants whose results of cognitive examination are abnormal but have not met the criteria for dementia. Participants will undergo annual clinical, epidemiological, and cognitive assessments, as well as biospecimen collection, for a duration of six years.	Diagnostic test: Plasma tau phosphorylated at Thr217; 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.; Other Names: S-PLEX Human Tau (pT217) Kit; ALZpath pTau-217 CARe Advantage Kit; Other: Neurocognitive examination; 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.
Late onset dementia; This cohort includes participants with dementia whose symptoms onset after the age of 65. Participants will undergo annual clinical, epidemiological, and cognitive assessments, as well as biospecimen collection, for a duration of two years.	Diagnostic test: Plasma tau phosphorylated at Thr217; 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.; Other Names: S-PLEX Human Tau (pT217) Kit; ALZpath pTau-217 CARe Advantage Kit; Other: Neurocognitive examination; 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.
Early onset dementia; This cohort includes participants with dementia whose symptoms onset before the age of 65. Participants will undergo annual clinical, epidemiological, and cognitive assessments, as well as biospecimen collection, for a duration of six years.	Diagnostic test: Plasma tau phosphorylated at Thr217; 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.; Other Names: S-PLEX Human Tau (pT217) Kit; ALZpath pTau-217 CARe Advantage Kit; Other: Neurocognitive examination; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	At 2, 4, 6 and 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	within 6 months of baseline measurement
Quantitative amyloid PET uptake.	Amyloid PET uptake tracer uptake quantified in Centiloids.	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.	within 6 months of baseline measurement
Future diagnosis of Alzheimer's disease dementia.	All of the following: 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.; 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.; Conclusion made by a neurologist with special interests in neurocognitive disorders that dementia is predominately due to Alzheimer's disease.	At 2, 4, 6 and 8 years
Changes in the Montreal Cognitive Assessment	Administered by a certified psychologist. Minimum value: 0 Maximum value: 30 Higher scores mean a better outcome.	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.	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.	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.	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.	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.	At 2, 4, 6 and 8 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life (WHOQOL-BREF)	Quality of life as measured by the Thai version of the WHOQOL-BREF questionnaire. The scales of 0-100 were subclassified for each QOL domain (ie. physical, psychological, social and environmental).	within 14 days of baseline measurement
Quality of life (EQ-5D-5L)	Quality of life as measured by the Thai version of the EQ-5D-5L questionnaire. The raw scores were transformed to utility scores for Thai population as previously suggested (Pattanaphesaj J., 2018).	within 14 days of baseline measurement
Number of modifiable risk factors	Count data of 0-12. Number of risk factors of the following 12 modifiable risk factors still present in a participant.; Untreated hearing impairment; High depression screening score; Active smoker; Social isolation; Untreated hypertension; Obesity; Untreated diabetes; Physical inactivity quantified by International physical inactivity questionnaire; Alcohol consumption over 21 units per week; Average sleep duration less than 6 hours per night; Low vegetable intake less than 2 servings per week; High red meat or processed meat intake over 5 serving per week	Three months after disclosing the biomarker results.

Collaborators and Investigators

• Sponsor: King Chulalongkorn Memorial Hospital
• Collaborators: Health Systems Research Institute,Thailand
• Investigators: Principal Investigator: Thiravat Hemachudha, M.D., Chulalongkorn University

Publications and helpful links

General Publications

• Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.
• Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412-4. doi: 10.1212/wnl.43.11.2412-a. No abstract available.
• Cho H, Choi JY, Hwang MS, Kim YJ, Lee HM, Lee HS, Lee JH, Ryu YH, Lee MS, Lyoo CH. In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum. Ann Neurol. 2016 Aug;80(2):247-58. doi: 10.1002/ana.24711. Epub 2016 Jul 8.
• American Psychiatric Association. Neurocognitive disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). 2013.
• Pattanaphesaj J, Thavorncharoensap M, Ramos-Goni JM, Tongsiri S, Ingsrisawang L, Teerawattananon Y. The EQ-5D-5L Valuation study in Thailand. Expert Rev Pharmacoecon Outcomes Res. 2018 Oct;18(5):551-558. doi: 10.1080/14737167.2018.1494574. Epub 2018 Jul 6.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): August 24, 2035
• Study Completion (Estimated): August 24, 2035

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Neurocognitive Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Imidacloprid
• Other Study ID Numbers: 425/66

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No