PROMOTE: Promotion of the Mind Through Exercise

Study Overview
=================
Brief Summary
-----------------
The investigators will conduct a proof-of-concept study to provide preliminary evidence of efficacy of aerobic-based exercise training for maintaining cognitive function, executive function, and everyday function in adults with mild vascular cognitive impairment.

Detailed Description
-----------------
A total of 70 adults diagnosed with Ischaemic Vascular Cognitive Impairment (SIVCI) will be randomized to either a 6 month thrice weekly walking program or usual care. After 6 months of intervention, they will be followed for an additional 6 months. There will be three measurement sessions: baseline, 6 months (end of intervention period); and 12 months.

Official Title
-----------------
Role of Exercise on Cognition and Function in Seniors With Vascular Cognitive Impairment: A Randomized Controlled Trial

Conditions
-----------------
Vascular Cognitive Impairment

Intervention / Treatment
-----------------
* Behavioral: Aerobic-based exercise training
* Behavioral: CON (control; usual care)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The study will specifically recruit individuals who fulfill the diagnostic criteria for SIVCI as outlined by Erkinjuntti and colleagues (1), which requires the presence of both cognitive syndrome (as defined in Section A below) and small vessel ischaemic disease (as defined in Section B below). A. Cognitive Syndrome defined as: Dysexecutive Syndrome: Some impairment in goal formulation, initiation, planning, organizing, sequencing, executing, set-shifting and maintenance, or abstracting. Memory Deficit: Some impairment in recall, relative intact recognition, less severe forgetting, benefit from cues. Progression: Deterioration of A1 and A2 from a previous higher level of functioning that are not per se interfering with complex occupational and social activities. B. Small Vessel Ischaemic Disease defined as: Evidence of relevant cerebrovascular disease by brain imaging (in the last 12 months) defined as the presence of both: i. Periventricular and deep white matter lesions: Patchy areas of low attenuation (intermediate density between that of normal white matter and that of intraventricular cerebro-spinal fluid) or diffuse symmetrical areas of low attenuation with ill defined margins extending to the centrum semiovale plus at least one lacunar infarct (correlating to the white matter grading scale greater than 3 from the Cardiovascular Health Study) (2,3); and ii. Absence of cortical and/or cortico-sub-cortical non-lacunar territorial infarcts and watershed infarcts, haemorrhages indicating large vessel disease, signs of normal pressure hydrocephalus, or other specific causes of white matter lesions (e.g., multiple sclerosis, leukodystrophies, sarcoidosis, brain irradiation, etc). Presence or a history of neurological signs as evidence for cerebrovascular disease such as hemiparesis, lower facial weakness, Babinski sign, sensory deficit, dysarthria, gait disorder, extrapyramidal signs consistent with sub-cortical brain lesion(s). In addition, individuals must meet the following inclusion criteria: Montreal Cognitive Assessment (MoCA) (4) score less than 26 at screening; MMSE (5) score of > 20 at screening; Community-dwelling; Lives in Metro Vancouver; Have a caregiver, family member, or friend who interacts with him/her on a weekly basis; Able to comply with scheduled visits, treatment plan, and other trial procedures; Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity; Stable on a fixed dose of cognitive medications (e.g., donepezil, galantamine, rivastigmine, memantine, etc.) that is not expected to change during the 12-month study period, or, if they are not on any of these medications, they are not expected to start them during the 12-month study period; Provide a personally signed and dated informed consent document indicating that the individual (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. In addition, an assent form will be provided at baseline and again at regular intervals; Able to walk independently; and Must be in sufficient health to participate in study's aerobic-based exercise training program. This will be based on medical history, vital signs, physical examination by study physicians, and written recommendation by family physician indicating individual's appropriateness to participate in an aerobic-based exercise training program. Exclusion Criteria: Absence of relevant small vessel ischaemic lesions on an existing brain computed tomography (CT) or MRI; Diagnosed with another type of dementia (e.g., AD) or other neurological conditions (e.g., multiple sclerosis, Parkinson's disease, etc.) that affects cognition and mobility; At high risk for cardiac complications during exercise and/or unable to self-regulate activity or to understand recommended activity level (i.e., Class C of the American Heart Risk Stratification Criteria); Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility; Taking medications that may negatively affect cognitive function, such as anticholinergics, including agents with pronounced anticholinergic properties (e.g., amitriptyline), major tranquilizers (typical and atypical antipsychotics), and anticonvulsants (e.g., gabapentin, valproic acid, etc.); or Individual who plans to participate or is enrolled in a clinical drug trial concurrent to this study.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AT (aerobic-based exercise training) | Behavioral: Aerobic-based exercise training<br>* Six months of thrice-weekly walking program that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).<br>|
| Active Comparator: 2<br>CON (control; usual care) | Behavioral: CON (control; usual care)<br>* Nutrition education and usual care as prescribed by neurologist<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This is a proof-of-concept study. The primary endpoints are: ADAS-Cog |  | baseline, 6 months, and 12 months | 
| EXIT-25 |  | baseline, 6 months, and 12 months | 
| ADCS-ADL |  | baseline, 6 months, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcomes of interest include: performance of specific executive processes |  | baseline, 6 months, and 12 months | 
| Physical function |  | baseline, 6 months, and 12 months | 
| Inflammatory biomarkers |  | baseline, 6 months, and 12 months | 
| Serum glucose and lipids. These will be assessed at 6 and 12 months. |  | baseline, 6 months, and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
exercise, aerobic exercise training, vascular cognitive impairment, Mild Sub-cortical Ischaemic Vascular Cognitive Impairment (SIVCI)