A Combined Multidomain Intervention to Prevent Cognitive Decline Associated With Cardiovascular Risk Factors.

Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning).

Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).

Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).

Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).

Variations of prefrontal cortical oxygen saturation (rSO2, [HbO]/([HbO]+[HbR])) will be measured by Near Infrared Spectroscopy (NIRS), as a surrogate of cortical blood flow. Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of oxygen saturation measures and variations of peripheral blood pressure.

Variations of cerebral blood flow velocity (cm/s) at the level of the middle cerebral artery will be measured by Transcranial Doppler (TCD). Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of cerebral blood flow measures and variations of peripheral blood pressure.

Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured by Arterial Spin Labeling MRI in two third of the study participants who do not present contra-indication for imaging studies.

Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using NIRS in the prefrontal region.

Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using TCD in the middle cerebral arteries

Pulsatility will be measured as the normalized difference of relative near-infrared light intensity changes between systole and diastole, using NIRS in the prefrontal cortical region.

Pulsatility will be measured as the normalized difference of relative blood flow velocities between systole and diastole, using TCD in the middle cerebral arteries.

Significant changes in brain activity evoked by a Stroop task relative to baseline will be assessed by t-statistics maps, computed from variations of [HbO] and [HbR] measured by NIRS at the prefrontal cortex.

Multimodal structural MRI will be performed in two third of the study participants who do not present contra-indication for imaging studies, to measure regional cerebral volumes, as well as volume of angiopathic markers (eg lacunes, microbleeds, white matter hyperintensities), in cm3.

Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)).

Fow-mediated dilation of the brachial artery (%).

Carotid femoral pulse-wave velocity (m/s).

Timed 10-meter walking test (cm/s).

Timed Time up and Go test (s).

Timed one-leg standing test (s).

Timed Sit-to-Stand test (s)

Grip strength test score (kg).

Total cholesterol levels (mmol/L)

Cholesterol-HDL levels (mmol/L)

Cholesterol-LDL calculated levels (mmol/L)

Cholesterol non-HDL levels (mmol/L)

Triglycerides levels (mmol/L)

Glucose levels (mmol/L)

Glycated hemoglobin (HbA1c) (%)

Insulin levels (pmol/L)

Creatinine levels (mg/dL)

Sodium levels (mmol/L)

Chloride levels (mmol/L)

Potassium levels (mmol/L)

High-sensitive C-reactive protein (hsCRP) levels (mg/L)

Apolipoprotein B (ApoB) levels (g/L)

Brain-derived neurotrophic factor (BDNF) plasma concentration (pg/mL).

Transcriptome analysis to assess the impact of the intervention on any changes in the activity of different cellular processes.

DNA extraction from fecal samples. The fecal samples will be collected from the participants who are also performing MRI.

Cortisol levels from saliva samples (nmol/L). The saliva samples will be collected from the participants who are also performing MRI.

Perceived Stress Scale questionnaire (Score ranges from 0-4, with 0 no stress,1 mild stress, 3 moderate stress and 4 severe).

State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).

Geriatric Depression Scale questionnaire (Score ranges from 0-30, with a higher score indicating larger depressive symptomatology).

12-Item Short Form Health Survey (a completer).

Pittsburg Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality).

Short Diet Questionnaire (Score ranges from 15-45 points, with a score between 15-29 categorised as unhealthy, 30-37 as somewhat unhealthy, and 38 or more as a healthy diet).

Social and community involvement questionnaire (Score ranges from 0-200, with a higher score indicating more social and community involvement).

Physical Activity Scale for the Elderly questionnaire (Score ranges from 0-400, with a higher score indicating better level of physical activity).

Short Form Bem Sex-Role Inventory questionnaire (30 items questionnaire with 10 items assessing the femininity traits, 10 items assessing the masculinity traits, and 10 items neutral, not scored. Two scores are calculated for femininity and masculinity, respectively, and range from 10-70, whit a higher score indicating a higher femininity or masculinity trait).

Genotyping array to generate high quality genome-wide genotyping data that include the APOE and BDNF genes.

Rami and colleagues' cognitive reserve questionnaire (Scale ranges from 0-26, with a higher score indicating a greater cognitive reserve).

Quantification of physical activity using an accelerometry recording of 7 days (minutes of moderate to vigorous activity).