Clinical trial NCT06375213: Investigating Neurocognitive Disorders Epidemiology
Official title: Investigating Neurocognitive Disorders Epidemiology
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dementia
Cognitive Decline
Alzheimer Disease
Lead sponsor: King Chulalongkorn Memorial Hospital
Sponsor class: OTHER
Collaborators: name: Health Systems Research Institute,Thailand
First posted: 2024-04-19
Enrollment: 990
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression to dementia
timeFrame: At 2, 4, 6 and 8 years
measure: Changes in Sum of Boxes of the Clinical Dementia Rating Scale
timeFrame: At 2, 4, 6 and 8 years
Secondary outcomes:
measure: Changes in the Montreal Cognitive Assessment
timeFrame: At 2, 4, 6 and 8 years
measure: Changes in the Montreal Cognitive Assessment - Memory Index Score
timeFrame: At 2, 4, 6 and 8 years
measure: Changes in the Mini Mental State Examination
timeFrame: At 2, 4, 6 and 8 years
measure: Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Visual Reproduction Scaled Score
timeFrame: At 2, 4, 6 and 8 years
measure: Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory Scaled Score
timeFrame: At 2, 4, 6 and 8 years
measure: Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Verbal Paired Associates Scaled Score
timeFrame: At 2, 4, 6 and 8 years
measure: Biological diagnosis of Alzheimer's disease
timeFrame: within 6 months of baseline measurement
measure: Biological staging of Alzheimer's disease
timeFrame: within 6 months of baseline measurement
measure: Quantitative amyloid PET uptake.
timeFrame: within 6 months of baseline measurement
measure: Quantitative tau PET uptake in various cortical regions.
timeFrame: within 6 months of baseline measurement
measure: Future diagnosis of Alzheimer's disease dementia.
timeFrame: At 2, 4, 6 and 8 years
Other outcomes:
measure: Quality of life (WHOQOL-BREF)
timeFrame: within 14 days of baseline measurement
measure: Quality of life (EQ-5D-5L)
timeFrame: within 14 days of baseline measurement
measure: Number of modifiable risk factors
timeFrame: Three months after disclosing the biomarker results.
Locations:
city: Pathum Wan
country: Thailand
facility: King Chulalongkorn Memorial Hospital
state: Bangkok
Study officials:
affiliation: Chulalongkorn University
name: Thiravat Hemachudha, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: American Psychiatric Association. Neurocognitive disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). 2013.
citation: 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.