Reducing Sedentary Time in Patients With Mild Cognitive Impairment: The Take a STAND for Health Study

Study Overview
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Brief Summary
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This research program aims to comprehensively investigate the clinical, physiological, metabolic, and molecular effects of reducing sedentary behavior in patients with mild cognitive impairment. A 4-month parallel-group randomized controlled trial will be conducted aiming to investigate the feasibility and efficacy of a newly developed personalized intervention focused on replacing sedentary time with light-(or very light-) intensity physical activity in patients with mild cognitive impairment. Additionally, a sub-sample of patients will complete a randomised cross-over study aiming to unravel potential mechanisms underlying the metabolic, physiological and molecular effects of breaking up sedentary time with light-intensity physical activity versus carrying out the minimum amount of daily exercise at once and then remaining sedentary versus simply remaining sedentary throughout all sessions, in a well-controlled laboratorial condition.

Official Title
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Reducing Sedentary Time in Patients With Mild Cognitive Impairment: The Take a STAND for Health Study TS4H-MCI

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Take a STAND for health


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Middle-aged and older adults with mild cognitive impairment confirmed by a team of neurologists from the CEREDIC HC-FMUSP Exclusion Criteria: Patients who spend less than 8 hours per day in sedentary time Patients who are physically active (more than 150 min/week of moderate physical activity, or more than 75 min/week of vigorous activity) Patients who are functional illiterates Patients with history or clinical diagnosis of neurological diseases Patients with severe psychiatric symptoms Patients taking antidepressants Patients with visual and/or hearing impairments that prevent participation

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A 4-month parallel-group randomised controlled trial will be performed, in which patients with mild cognitive impairment will be assessed at baseline (PRE) and after 4 months (POST). Moreover, a sub-sample of patients will perform a randomised crossover trial at baseline (PRE). Patients will complete three experimental sessions in a random manner, as follows: Prolonged sitting (SIT), in which participants engaged in prolonged sitting throughout an 5-h period and were instructed to minimize excessive movement; Exercise followed by prolonged sitting (EX), in which participants performed a 30-min moderate-to-vigorous exercise bout on a treadmill, subsequently, participants engaged in prolonged sitting as described for SIT; Light-intensity breaks (BR), in which participants completed a 3-min bout of light-intensity walking every 30 min of sitting throughout the experimental period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Take a STAND for health<br>A newly developed personalized intervention focused on replacing sedentary time with light-(or very light-) intensity physical activity | Behavioral: Take a STAND for health<br>* The Take a STAND for health is a newly developed 4-month goal-setting intervention aimed at reducing sedentary behavior<br>|
| No Intervention: Control<br>The control group will receive regular medical care and advice on healthy lifestyle, including physical activity and healthy eating recommendations | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sedentary behaviour assessed by ActivPAL™ |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity levels assessed by ActiGraph GT3X® |  | 4 months | 
| Cognitive performance assessed by the Montreal Cognitive Assessment (MoCA) | Questionnaire to be completed by the patient. Final score 0 to 30, lower scores indicate worse cognitive performance | 4 months | 
| Cognitive decline assessed by the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) | Questionnaire to be completed by the caregiver. 26 Likert scale questions. Higher scores indicate worse cognitive performance | 4 months | 
| Subjective memory complaints assessed by the Memory Complaint Scale (MCS) | Questionnaire to be completed by the patient and the caregiver. Final scores classify memory complaints as absent, mild, moderate or accentuated | 4 months | 
| Functional impairments in activities of daily living assessed by the Functional Activities Questionnaire (FAQ) | Questionnaire to be completed by the caregiver. Final score 0 to 30, higher scores indicate greater functional dependency | 4 months | 
| Anxiety symptoms assessed by the Geriatric Anxiety Inventory (GAI) | Questionnaire to be completed by the patient. Final score 0 to 20, higher scores indicate greater anxiety symptoms | 4 months | 
| Depression symptoms assessed by the Geriatric Depression Scale (GDS-15) | Questionnaire to be completed by the patient. Final score 0 to 15, higher scores indicate greater depression symptoms | 4 months | 
| Neurocognitive assessment assessed by the Cogstate Research™ (Cogstate, Melbourne, AUS) | Reliable online system that assesses verbal learning capacity, executive function, processing speed, attention capacity, reaction time, and operational memory. Final score will be generated automatically by the system | 4 months | 
| Magnetic resonance imaging using the Philips ACHIEVA 3.0 Tesla | The following sequences will be obtained: 1 - sagittal 3D T1; 2 - axial T2 fast spin echo (FSE); 3 - axial fluid-attenuated inversion recovery (FLAIR); 4 - coronal T2 spectral presaturation with inversion recovery (SPIR); 5 - coronal T2 aligned with hippocampus; 6 - SENSE diffusion | 4 months | 
| Positron emission computed tomography with 18F-fluordesoxyglucose (PET-18FDG) using the Biograph, CTI/Siemens, Knowville, EUA | Tomographic sections will be acquired for 15 minutes with a 256x256 matrix, zoom 2.5, resulting in pixels of size 1.04 mm (voxel of 1.04 mm3). The images will be reconstructed using the ordered subset expectation maximization (OSEM) iterative method, with six iterations and 16 subsets, and smoothed with a 5 mm Gaussian filter. The data will be corrected for scattering, attenuation and decay | 4 months | 
| Assessment of cerebrovascular reactivity to CO2 inhalation | Patients will wear a mask connected to a unidirectional valve with a Douglas bag (with 5% CO2). Evaluations will include: partial pressure of carbon dioxide at the end of expiration (PetO2, PetCO2) (Metalyzer model III b/breath-by-breath, CORTEX, Germany) and O2 saturation (SpO2; Nellcor, Medtronic Corporation, USA). Blood flow and diameter of the internal carotid artery will be assessed using a Doppler ultrasound (Logiq E, General Electric, Milwaukee, USA) connected to a linear transducer (12L-RS - 5.0-13.0 MHz). Cerebrovascular reactivity will be assessed by responses of arterial diameter, blood flow and shear rate to CO2 inhalation (reactivity = peak - baseline). A software with automatic detection of the artery walls will be used (Cardiovascular Suite, Quipu®, Pisa, Italy). Blood flow will be calculated (Flow = Vm x πr2 x 60). The shear rate will be calculated using the following formula: Shear rate = 8 x Vm / diameter | 4 months | 
| Muscle functional assessed by the Timed Stands Test and the Timed Up-and-Go Test | Test results will be combined to report muscle function | 4 months | 
| Handgrip strength assessed by a hand dynamometer | Patient will have three 5-second trials, with 1-minute interval between trials. Best score will be considered handgrip strength | 4 months | 
| Blood pressure |  | 4 months | 
| Fatigue severity assessed by the Fatigue Severity Scale (FSS) |  | 4 months | 
| Physical and mental aspects of fatigue assessed by the Chalder Fatigue Scale (CFS) |  | 4 months | 
| Subjective sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) |  | 4 months | 
| Daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) |  | 4 months | 
| Quality of life assessed by the SF-36 (Medical Outcomes Study 36 - Short-Form Health Survey) |  | 4 months | 
| Food consumption | 24-hour dietary recalls | 4 months | 
| Insulin sensitivity | Fasting serum concentrations of glucose, insulin | 4 months | 
| Lipid profile | Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides | 4 months | 
| Inflammatory cytokines | pro- and anti-inflammatory cytokines: IL-1, IL-1ra, IL-6, IL-10 e TNF-alpha | 4 months | 
| Genetic profile for Alzheimer's disease | Genotyping of apolipoprotein E (ApoE) | 4 months | 
| Oral glucose tolerance test | Fasting, 30, 60, 90, and 120 minutes | 4 months |