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

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.

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.

Executive function measured using mNTB subtests: Digit Span, Word and Category Fluency test, Trail Making Test Part B.

Processing speed measured using mNTB subtests: Letter Digit Substitution test and Trail-Making Test Part A.

The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is scored from 0 to 18. Higher scores reflect worse performance.

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.

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.

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'.

The Prospective-Retrospective Memory Questionnaire (PRMQ) is measured on a 5-point scale. Higher scores represent greater frequency of memory failures.

The Pittsburgh Sleep Quality Index (PSQI) is scored from 0 to 21. Higher scores indicate worse sleep quality.

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.

The Physical Performance Test (PPT) is scored from 0 to 36. Higher scores represent better performance.

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.

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.

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.

Height is measured in metres.

Weight is measured in kilograms.

Hip and waist circumference measured in centimetres.

Vascular and metabolic risk factors measured by changes in blood pressure in mmHg. Incident events using serious adverse event reports will also be assessed.

Vascular and metabolic risk factors measured by changes in lipid profile in mmol/L.

Vascular and metabolic risk factors measured by changes in glucose regulation in mmol/L.

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.

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.

Multimodal retinal imaging will be used to assess retinal structural, vascular and neuronal changes.