Investigating Neurocognitive Disorders Epidemiology

Alzheimer Disease Clinical Trial

— INDE  

Official title:

Investigating Neurocognitive Disorders Epidemiology

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06375213
• Other study ID #: 425/66
• Status: Recruiting
• Start date: August 24, 2023
• Est. completion date: August 24, 2035

Study information

• Verified date: April 2024
• Source: King Chulalongkorn Memorial Hospital
• Contact: Poosanu Thanapornsangsuth, M.D.
• Phone: +66 (0)2 2564000
• Email: poosanu.t[@]chula.ac.th
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 990
• Est. completion date: August 24, 2035
• Est. primary completion date: August 24, 2035
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Decline
• Cognitive Dysfunction
• Dementia
• Neurocognitive Disorders

Intervention

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.

Locations

Country	Name	City	State
Thailand	King Chulalongkorn Memorial Hospital	Pathum Wan	Bangkok

Sponsors (2)

Lead Sponsor	Collaborator
King Chulalongkorn Memorial Hospital	Health Systems Research Institute,Thailand

Country where clinical trial is conducted

Thailand, 

References & Publications (5)

American Psychiatric Association. Neurocognitive disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). 2013.

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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.
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Quantitative amyloid PET uptake.	Amyloid PET uptake tracer uptake quantified in Centiloids.	within 6 months of baseline measurement
Secondary	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
Secondary	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