The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study

Study Overview
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Brief Summary
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A study in Finland found that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities and management of vascular risk factors slowed cognitive decline in healthy older adults at increased risk of cognitive decline. A 6-month pilot study was initiated in Singapore, which demonstrated the cultural feasibility and practicality of the FINGER interventions and a set of locally adapted interventions in an Asian population. The SINGER study is a 2-year randomized controlled trial that aims to test the efficacy and safety of these lifestyle changes, including diet and cardiovascular risk factor management, cognitive and physical exercises, in delaying cognitive decline in older adults at risk of dementia.

Detailed Description
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Results from a population-based 2-year clinical trial, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), demonstrated that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities and management of vascular risk factors slowed cognitive decline in healthy older adults at increased risk of cognitive decline. Currently, no pharmacological treatment options that can rival these effects. Thus, there is an urgent need to test the generalizability, adaptability, and sustainability of these findings in Singaporean populations. A 6-month pilot study was initiated in Singapore, which demonstrated the cultural feasibility and practicality of the FINGER interventions and a set of locally adapted interventions in an Asian population. Hence, the next step was to conduct a larger scale SINGER trial to determine the efficacy of these interventions in Singapore. If the interventions are found to be effective and safe with high applicability and scalability, the study will provide important clinical and public health implications to a rapidly increasing ageing population.

Official Title
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The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study, Biomarker and Health Service Research Analyses

Conditions
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Cognitive Impairment, Alzheimer Disease, Vascular Cognitive Impairment, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurocognitive Disorders, Mental Disorders, Cognition Disorder

Intervention / Treatment
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* Behavioral: Structured Lifestyle Intervention
* Behavioral: Self-Guided Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60-77 years Able to understand English/Chinese Risk of dementia: Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score >6 indicating the presence of modifiable risk factors Modifiable lifestyle factors (fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity) Cognitive performance at the mean level or slightly lower than expected for age (MoCA ≥18, ≤27) No plans to travel outside of Singapore for an extended period of time over the course of the study Free of physical disabilities that preclude participation in the study Willing to complete all study-related activities for 24 months Willing to be randomized to either lifestyle intervention group Exclusion Criteria: malignant diseases dementia substantial cognitive decline (MoCA<18) major depression symptomatic cardiovascular disease revascularisation within 1 year severe loss of vision, hearing or communicative ability other conditions inhibiting from safe engagement in the prescribed intervention and other conditions preventing cooperation, as judged by the study physician

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 77 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Structured Lifestyle Intervention<br>Structured lifestyle modification program developed for participants targeting diet, physical exercise, cognitive training, and social stimulation. | Behavioral: Structured Lifestyle Intervention<br>* Structured Lifestyle Intervention (SLI) involves providing participants with intensive structure and support by a team of trainers to increase physical exercise, adhere to a healthy diet, cognitive training, increase intellectual/social stimulation, and better manage vascular risk factors.<br>* Other names: SLI;|
| Experimental: Self-Guided Intervention<br>General health information provided to participants. | Behavioral: Self-Guided Intervention<br>* In the Self-Guided Intervention (SGI), education about the importance of a healthy lifestyle as a preventive strategy and support to encourage change will be provided.<br>* Other names: SGI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Cognition | Global cognition measured using the modified Neuropsychological Test Battery (mNTB) that includes: Visual Paired Associates, Logical Memory Recall of the Wechsler Memory Scale-Revised, Rey Auditory Verbal Learning, Digit Span, Word and Category Fluency test, Trail Making Test, Letter Digit Substitution test. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Episodic Memory | Episodic memory measured using mNTB subtests: Visual paired associates tests, Logical Memory immediate and delayed recall of the Wechsler Memory Scale-Revised, Rey Auditory Verbal Learning test. | Up to 2 years | 
| Executive Function | Executive function measured using mNTB subtests: Digit Span, Word and Category Fluency test, Trail Making Test Part B. | Up to 2 years | 
| Processing Speed | Processing speed measured using mNTB subtests: Letter Digit Substitution test and Trail-Making Test Part A. | Up to 2 years | 
| Clinical Dementia Rating-Sum of Boxes (CDR-SB) | The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is scored from 0 to 18. Higher scores reflect worse performance. | Up to 2 years | 
| Alzheimer's Disease Cooperative Study Activities of Daily Living-Mild Cognitive Impairment-Activities of Daily Living Inventory (ADCS-MCI-ADL) | The Alzheimer's Disease Cooperative Study Activities of Daily Living-Mild Cognitive Impairment-Activities of Daily Living Inventory (ADCS-MCI-ADL) is scored from 0 to 53. Higher scores reflect better performance. | Up to 2 years | 
| The Geriatric Depression Scale (GDS) | The Geriatric Depression Scale (GDS) is scored from 0 to 15. Scores of 0-4 are considered normal, 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression. | Up to 2 years | 
| Global Physical Activity Questionnaire (GPAQ) | The Global Physical Activity Questionnaire (GPAQ) measures physical activity across 3 domains: work, travel, and recreation, as well as average time per day spent in sedentary behavior. The GPAQ is scored based on a population's mean or median physical activity spent in physical activity or by classifying a certain percentage of a population as 'inactive' or 'insufficiently active'. | Up to 2 years | 
| Prospective-Retrospective Memory Questionnaire | The Prospective-Retrospective Memory Questionnaire (PRMQ) is measured on a 5-point scale. Higher scores represent greater frequency of memory failures. | Up to 2 years | 
| Pittsburgh Sleep Quality Index (PSQI) | The Pittsburgh Sleep Quality Index (PSQI) is scored from 0 to 21. Higher scores indicate worse sleep quality. | Up to 2 years | 
| Leisure-Time Activities Questionnaire | The Leisure-Time Activities Questionnaire measures the frequency of engagement in the following activities: Health activities, Social activities, Productive activities, Fitness activities, Recreational activities, Any cognitively-stimulating activities. Scores are measured on a 3-point scale. Higher scores represent higher frequency of engagement in leisure-time activities. | Up to 2 years | 
| Physical Performance Test (PPT) | The Physical Performance Test (PPT) is scored from 0 to 36. Higher scores represent better performance. | Up to 2 years | 
| Quality of Life Questionnaire (15D) | The Quality of Life Questionnaire (15D) has a single index (15D score) on a 0-1 scale, which represents overall HRQoL (0 = being dead, 0.0162 = being unconscious or comatose, 1 = no problems on any dimension = 'full' HRQOL). This is calculated from the health state descriptive system by using a set of population-based preference or utility weights. | Up to 2 years | 
| 36-Item Short Form Survey (SF-36) | The 36-Item Short Form Survey (SF-36) has eight domains. Each domain is scored from 0 to 100. Higher scores represent a more favourable health state. | Up to 2 years | 
| Resource Use Inventory (RUI) | The Resource Use Inventory (RUI) measures 4 domains: direct medical care, direct nonmedical care, informal care, and subjects' time use. The RUI is filled in based on the frequency and amount of resources used. If none were used, '00' is entered. | Up to 2 years | 
| Height | Height is measured in metres. | Up to 2 years | 
| Weight | Weight is measured in kilograms. | Up to 2 years | 
| Hip and waist circumference | Hip and waist circumference measured in centimetres. | Up to 2 years | 
| Changes in Blood Pressure | Vascular and metabolic risk factors measured by changes in blood pressure in mmHg. Incident events using serious adverse event reports will also be assessed. | Up to 2 years | 
| Changes in Lipid Profile | Vascular and metabolic risk factors measured by changes in lipid profile in mmol/L. | Up to 2 years | 
| Changes in Glucose Regulation | Vascular and metabolic risk factors measured by changes in glucose regulation in mmol/L. | Up to 2 years | 
| Neuroimaging | Magnetic Resonance Imaging will be used to assess changes in brain structural integrity, grey matter volume loss, white matter microstructure degradation, and increase of cerebrovascular disease markers (CeVD). Vascular polygenic risk scores (PRS) and its association with neurodegeneration, CeVD burden and cognitive decline will be performed. | Up to 2 years | 
| Blood Biomarkers | Novel and accessible blood markers to monitor AD- and CeVD-associated pathologies will be measured. Plasma concentrations of cardiac markers (High-sensitive cardiac troponin T (hs Troponin T), N-terminal pro b-type natriuretic peptide (NT-proBNP) and Growth/differentiation factor 15 (GDF 15)), and peripheral biomarkers of Aβ, tau and synaptic pathology, oxidative stress, endothelial/cardiovascular injury and degenerative protein modifications (DPMs) damaged proteins will be used. | Up to 2 years | 
| Retinal Imaging Markers | Multimodal retinal imaging will be used to assess retinal structural, vascular and neuronal changes. | Baseline only | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dementia, cognitive decline, cognitive impairment, multi-domain lifestyle interventions, elderly