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

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

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.

Study Overview

• Status: Completed
• Conditions: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Cognitive Impairment; Dementia; Alzheimer Disease; Cognition Disorder; Vascular Cognitive Impairment
• Intervention / Treatment: Behavioral: Structured Lifestyle Intervention; Behavioral: Self-Guided Intervention

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1212
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore
    • Singapore, Singapore, Singapore, 117600
      • National University Hospital
    • Singapore, Singapore, Singapore, 117600
      • National University of Singapore, Yong Loo Lin School of Medicine
    • Singapore, Singapore, Singapore, 308433
      • National Neuroscience Institute @ Tan Tock Seng Campus (NNI @ TTSH campus)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 60-80 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
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Structured Lifestyle Intervention; Structured lifestyle modification program developed for participants targeting diet, physical exercise, cognitive training, and social stimulation.	Behavioral: Structured Lifestyle Intervention; 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.; Other Names: SLI
Experimental: Self-Guided Intervention; General health information provided to participants.	Behavioral: Self-Guided Intervention; 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.; Other Names: SGI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National University of Singapore
• Collaborators: National Medical Research Council (NMRC), Singapore
• Investigators: Principal Investigator: Christopher LH Chen, MD, National University of Singapore

Publications and helpful links

General Publications

• Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.
• Chew KA, Xu X, Siongco P, Villaraza S, Phua AKS, Wong ZX, Chung CY, Tang N, Chew E, Henry CJ, Koo E, Chen C. SINgapore GERiatric intervention study to reduce physical frailty and cognitive decline (SINGER)-pilot: A feasibility study. Alzheimers Dement (N Y). 2021 Mar 15;7(1):e12141. doi: 10.1002/trc2.12141. eCollection 2021.
• Yap KH, Chen C, Chong EJY, Kandiah N, Kivipelto M, Lai MKP, Maier AB, Matchar DB, Phua AKS, Teo CKL, Xu X, Zhou HJ, Chen CPL. Baseline characteristics of the SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) multidomain dementia prevention randomized controlled trial and insights from the recruitment process. Alzheimers Dement. 2026 Apr;22(4):e71313. doi: 10.1002/alz.71313.
• Ooi LQR, Orban C, Zhang S, Nichols TE, Tan TWK, Kong R, Marek S, Dosenbach NUF, Laumann TO, Gordon EM, Yap KH, Ji F, Chong JSX, Chen C, An L, Franzmeier N, Roemer-Cassiano SN, Hu Q, Ren J, Liu H, Chopra S, Cocuzza CV, Baker JT, Zhou JH, Bzdok D, Eickhoff SB, Holmes AJ, Yeo BTT; Alzheimer's Disease Neuroimaging Initiative. Longer scans boost prediction and cut costs in brain-wide association studies. Nature. 2025 Aug;644(8077):731-740. doi: 10.1038/s41586-025-09250-1. Epub 2025 Jul 16.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2021
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: July 28, 2021
• First Submitted That Met QC Criteria: August 10, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: dementia; elderly; cognitive decline; cognitive impairment; multi-domain lifestyle interventions
• Additional Relevant MeSH Terms: Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Mental Disorders; Dementia; Brain Diseases; Nervous System Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Cognition Disorders
• Other Study ID Numbers: SINGER 2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Interested collaborators may put in a request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No