Investigating Neurocognitive Disorders Epidemiology

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.

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.

Interventions

• 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 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.

Primary outcome measures

• Progression to dementia [Time frame: At 2, 4, 6 and 8 years]
• Changes in Sum of Boxes of the Clinical Dementia Rating Scale [Time frame: At 2, 4, 6 and 8 years]

Secondary outcome measures (11)

• Changes in the Montreal Cognitive Assessment [Time frame: At 2, 4, 6 and 8 years]
• Changes in the Montreal Cognitive Assessment - Memory Index Score [Time frame: At 2, 4, 6 and 8 years]
• Changes in the Mini Mental State Examination [Time frame: At 2, 4, 6 and 8 years]
• Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Visual Reproduction Scaled Score [Time frame: At 2, 4, 6 and 8 years]
• Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory Scaled Score [Time frame: At 2, 4, 6 and 8 years]
• Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Verbal Paired Associates Scaled Score [Time frame: At 2, 4, 6 and 8 years]
• Biological diagnosis of Alzheimer's disease [Time frame: within 6 months of baseline measurement]
• Biological staging of Alzheimer's disease [Time frame: within 6 months of baseline measurement]
• Quantitative amyloid PET uptake. [Time frame: within 6 months of baseline measurement]
• Quantitative tau PET uptake in various cortical regions. [Time frame: within 6 months of baseline measurement]
• Future diagnosis of Alzheimer's disease dementia. [Time frame: At 2, 4, 6 and 8 years]

Eligibility criteria

• 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.
• 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.
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Thailand · 1 center

• King Chulalongkorn Memorial Hospital — Pathum Wan

Publications

• 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. PMID 27323247
• 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. PMID 8232972
• 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. PMID 29653606
• 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. PMID 29958008

Identifiers

NCT: NCT06375213 · 425/66

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗