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Investigating Neurocognitive Disorders Epidemiology

Recruiting
Conditions
Dementia
Alzheimer Disease
Cognitive Decline
Interventions
Diagnostic Test: Plasma tau phosphorylated at Thr217
Other: Neurocognitive examination
Registration Number
NCT06375213
Lead Sponsor
King Chulalongkorn Memorial Hospital
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
990
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Early onset dementiaNeurocognitive examinationThis 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.
Mild cognitive impairmentNeurocognitive examinationThis 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.
Cognitively healthyNeurocognitive examinationThis 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.
Late onset dementiaPlasma tau phosphorylated at Thr217This 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.
Late onset dementiaNeurocognitive examinationThis 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.
Mild cognitive impairmentPlasma tau phosphorylated at Thr217This 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.
Early onset dementiaPlasma tau phosphorylated at Thr217This 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.
Cognitively healthyPlasma tau phosphorylated at Thr217This 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.
Primary Outcome Measures
NameTimeMethod
Changes in Sum of Boxes of the Clinical Dementia Rating ScaleAt 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.

Progression to dementiaAt 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.

Secondary Outcome Measures
NameTimeMethod
Biological diagnosis of Alzheimer's diseasewithin 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.

Changes in the Mini Mental State ExaminationAt 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 Montreal Cognitive AssessmentAt 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) Logical Memory Scaled ScoreAt 2, 4, 6 and 8 years

Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 Higher scores mean a better outcome.

Biological staging of Alzheimer's diseasewithin 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.

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.

Changes in the Montreal Cognitive Assessment - Memory Index ScoreAt 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 Wechsler Memory Scale - Fourth Edition (WMS-IV) Visual Reproduction Scaled ScoreAt 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 ScoreAt 2, 4, 6 and 8 years

Administered by a certified psychologist. Minimum value: 1 Maximum value: 19 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.

Trial Locations

Locations (1)

King Chulalongkorn Memorial Hospital

🇹🇭

Pathum Wan, Bangkok, Thailand

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