Alzheimer Disease, Cognitive Decline, Dementia
Conditions
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.
Interventions
DIAGNOSTIC_TESTPlasma 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.
OTHERNeurocognitive 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.
Sponsors
Health Systems Research Institute,Thailand
King Chulalongkorn Memorial Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression to dementia | At 2, 4, 6 and 8 years | 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. |
| Changes in Sum of Boxes of the Clinical Dementia Rating Scale | At 2, 4, 6 and 8 years | Administered by a certified psychologist in accordance with Morris, J.C. (1993). Minimum value: 0 Maximum value: 18 Higher scores mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Montreal Cognitive Assessment - Memory Index Score | At 2, 4, 6 and 8 years | Administered by a certified psychologist. Minimum value: 0 Maximum value: 15 Higher scores mean a better outcome. |
| Changes in the Mini Mental State Examination | At 2, 4, 6 and 8 years | Administered by a certified psychologist. Minimum value: 0 Maximum value: 30 Higher scores mean a better outcome. |
| Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Visual Reproduction Scaled Score | At 2, 4, 6 and 8 years | Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome. |
| Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Logical Memory Scaled Score | At 2, 4, 6 and 8 years | Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome. |
| Changes in the Wechsler Memory Scale - Fourth Edition (WMS-IV) Verbal Paired Associates Scaled Score | At 2, 4, 6 and 8 years | Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome. |
| Changes in the Montreal Cognitive Assessment | At 2, 4, 6 and 8 years | Administered by a certified psychologist. Minimum value: 0 Maximum value: 30 Higher scores mean a better outcome. |
| Quantitative amyloid PET uptake. | within 6 months of baseline measurement | Amyloid PET uptake tracer uptake quantified in Centiloids. |
| Quantitative tau PET uptake in various cortical regions. | within 6 months of baseline measurement | 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. |
| Future diagnosis of Alzheimer's disease dementia. | At 2, 4, 6 and 8 years | 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. |
| Biological diagnosis of Alzheimer's disease | within 6 months of baseline measurement | 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. |
| Biological staging of Alzheimer's disease | within 6 months of baseline measurement | Staging of Alzheimer's disease based on the abnormality of pathology-specific biomarkers according to the current NIA-AA criteria. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life (WHOQOL-BREF) | within 14 days of baseline measurement | 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). |
| Quality of life (EQ-5D-5L) | within 14 days of baseline measurement | 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). |
| Number of modifiable risk factors | Three months after disclosing the biomarker results. | Count data of 0-12. Number of risk factors of the following 12 modifiable risk factors still present in a participant. 1. Untreated hearing impairment 2. High depression screening score 3. Active smoker 4. Social isolation 5. Untreated hypertension 6. Obesity 7. Untreated diabetes 8. Physical inactivity quantified by International physical inactivity questionnaire 9. Alcohol consumption over 21 units per week 10. Average sleep duration less than 6 hours per night 11. Low vegetable intake less than 2 servings per week 12. High red meat or processed meat intake over 5 serving per week |
Countries
Thailand
Contacts
Primary ContactPoosanu Thanapornsangsuth, M.D.
Backup ContactThanakit Pongpitakmetha, M.D.
Outcome results
None listed