A Multi-domain Lifestyle Intervention Among Aged Community-residents in Zhejiang, China

Globe cognitive performance (composite z-score) measured by comprehensive Neuropsychological Test Battery (NTB)

NTB domain-specific cognitive performance (composite z-score) for memory, executive function, attention, language, visuomotor speed and visuoconstruction.

Changes in brain blood flow assessed by magnetic resonance angiography(MRA)

Changes in brain structural integrity (gray matter volume loss, white matter microstructure degradation and increase of cerebrovascular markers) assessed by T1-weighted Magnetization Prepared Rapid Gradient Recalled Echo, Fluid Attenuated Inversion Recovery (FLAIR), T2-weighted, and Susceptibility Weighted Imaging sequences

Changes in brain functional networks assessed by fMRI

Blood samples will be collected from all patients in tubes with ethylenediaminetetraacetic acid 0.1%. Changes in Novel and accessible blood markers to monitor AD- and CeVD- associated pathologies. 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 measured by laboratory testings.

Incidence of dementia. Dementia diagnoses will be made by CDR and DSM-IV criteria.

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.

Physician-diagnosed cardiometabolic health disorders will be identified based on ICD-9 or ICD-10 codes (in any position). Any incident cardiometabolic morbidity, for example, ardiac dysrhythmias, heart failure, peripheral and visceral atherosclerosis, non-alcoholic fatty liver disease, chronic kidney disease, type 2 diabetes, hypercholesterolemia, and hypertension, will be recorded.

Grip strength will be assessed by a hydraulic hand dynamometer and expressed in absolute units(kilograms) andrelative units(kilograms divided by bodyweight).

Walking pace will be assessed by the speed (m/second) of completing a 1.5 meters walk.

Balance will be measured by standing on one foot and expressed in absolute units(seconds).

Endurance will be assessed by the 2MW. Participants will be asked to "walk as fast as you can without running" for 2 minutes around a 50-foot course. A greater distance(m) indicates better endurance.

Lower limb strength will be assessed by 30 second sit to stand test and expressed by completion times.

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 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 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 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 will be measured in metres

Weight will be measured in kilograms.

Hip circumference will be measured in centimetres.

Waist circumference will be 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.

Blood samples will be collected from all patients in tubes with ethylenediaminetetraacetic acid 0.1%. Lipid Profile will be expressed by total cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides in mmol/L.

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

Retinal fundus photographs will be taken of each eye with a nonmydriatic digital camera after dilation of pupils with 1% tropicamide eye drops. A semi-automated computer-assisted program will be used to assess retinal vascular fractal dimensions (among other parameters such as vessel caliber and vessel tortuosity) from optic disc-centered images of a randomly selected eye per participant.

Prospective rate of falls, causes and consequences via monthly calendar will be recorded.