We will recruit individuals who fulfill the diagnostic criteria for SIVCI as outlined by Erkinjuntti and colleagues , 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:
1. Dysexecutive Syndrome: Some impairment in goal formulation, initiation, planning, organizing, sequencing, executing, set-shifting and maintenance, or abstracting.
2. Memory Deficit: Some impairment in recall in the presence of relatively intact recognition and benefit from cueing.
3. 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:
1. Evidence of relevant cerebrovascular disease by brain imaging (in the last 12 months) defined as the presence of both:
Periventricular and deep white matter lesions: Patchy areas of low attenuation (intermediate density between that of normal white matter and that of intraventricular cerebrospinal 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) [23, 24]; and
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).
2. Presence or a history of neurological signs as evidence for cerebrovascular disease such as lower facial weakness, Babinski sign, sensory deficit, dysarthria, gait disorder, or extrapyramidal signs consistent with sub-cortical brain lesion(s).
In addition, individuals must meet the following inclusion criteria: 1) Montreal Cognitive Assessment (MoCA)  score less than 26 at screening; 2) Mini-Mental State Examination (MMSE)  score of ≥ 20 at screening; 3) Community-dwelling; 4) Live in Metro Vancouver; 5) Have a caregiver, family member, or friend who interacts with him/her on a weekly basis; 6) Able to comply with scheduled visits, treatment plan, and other trial procedures; 7) Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity; 8) 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; 9) 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; 10) Able to walk independently; and 11) Must be in sufficient health to participate in the 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 one's appropriateness to participate in an aerobic-based exercise training program.
The exclusion criteria are: 1) Absence of relevant small vessel ischaemic lesions on an existing brain computed tomography (CT) or magnetic resonance imaging (MRI); 2) Diagnosed with another type of neurodegenerative (e.g. AD) or neurological condition (e.g., multiple sclerosis, Parkinson's disease, etc.) that affects cognition and mobility; 3) 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); 4) Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility; 5) 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 6) Planning to participate, or already enrolled in, a clinical drug trial concurrent to this study.
Ethical approval has been obtained from the Vancouver Coastal Health Research Institute (V07-01160) and the University of British Columbia's Clinical Research Ethics Board (H07-01160).
Baseline measurements will be obtained prior to randomization. There will be three measurement sessions: baseline, 6 months, and 12 months (Figure 1). Outcomes will be assessed by trained assessors blinded to group allocation.
For the screening session, we will administer the Physical Activity Readiness Questionnaire (PAR-Q) , a screening measure of physical readiness for exercise. Global cognitive function will be assessed using the MMSE  and the MoCA .
Using a wall mounted stadiometer, standing height will be measured as stretch stature to the 0.1 cm per standard protocol. Weight will be measured twice to the 0.1 kg on a calibrated digital scale. General health and socioeconomic status will be ascertained by a questionnaire. Participants will undergo a clinical assessment with neurologist and study physicians (G-YRH and PL) at baseline to confirm current health status and eligibility for study, including clinical impressions of overall cognitive and functional status. The Neuropsychiatric Inventory (NPI), an informant-rated instrument, will be used to evaluate behavioural and neuropsychiatric symptoms .
Physical activity, not including the study-assigned exercise classes, will be determined by the valid and reliable Physical Activities Scale for the Elderly (PASE) questionnaire [33, 34]. Designed for those aged 65 years and older, participants use a 12-item scale to self-report the average number of hours per day spent participating in leisure, household, and occupational physical activities over the previous seven-day period. Accounting for extracurricular physical activities throughout the randomized trial is essential to ascertain the specific effects of the delivered interventions on cognition and function.
We will assess cognitive function using the cognitive section of the Alzheimer Disease Assessment Scale (ADAS-Cog) . The scale consists of 11 brief cognitive tests assessing memory, language, and praxis. Scores range from 0 to 70, with higher scores indicating greater severity of cognitive impairment. The ADAS-Cog has been a significant outcome measure in numerous trials with AD [27, 36, 37] but also with vascular dementia [29, 38]. The ADAS-Cog has marked advantages as an outcome measure, based on its substantial data confirming both reliability and validity and its use in measuring longitudinal change together with sensitivity to treatment effects .
Global Executive Function
Because executive dysfunction is common among those with SIVCI , we will use the Executive Interview (EXIT-25)  to assess global executive function. The EXIT 25 provides a standardized clinical assessment of executive functions. It contains 25 items designed to elicit signs of frontal system pathology. Performance on the EXIT25 correlates well with standard neuropsychological tests of executive functions. The EXIT25 scores range from 0 to 50, with high scores indicating impaired global executive function. A cut point of 15 out of 50 is recommended .
Because executive dysfunction is associated with impaired everyday function , we will use the ADCS-ADL to assess the ability to perform everyday activities of daily living . The ADCS-ADL is a 23-item informant-rated questionnaire that measures, in a range of 0 to 78, an individual's performance of activities of daily living.
Serum glucose, Hgb A1c, and lipid level will be measured by conventional methods. Serum HSC, CRP, and IL-6 will be determined by standard ELISA methods .
Physical function will be assessed using a three-instrument performance battery that includes:
1) Six-Minute Walk
This is a walking test of physical status to assess general cardiovascular capacity in seniors . The total distance walked in meters in six minutes is recorded in meters.
2) Balance and Mobility
General balance and mobility will be assessed with the National Institute on Aging (NIA) Balance Scale . For this Scale, participants are assessed on performances of standing balance, walking, and sit-to-stand. Each component is rated out of four points, for a maximum of 12 points. Poor performance on this scale predicts subsequent disability .
3) Physiological Falls Risk
We will use the Physiological Profile Assessment (PPA)©  (Prince of Wales Medical Research Institute, Randwick, Sydney, NSW, Australia) to assess for physiological falls risk. The PPA is a valid and reliable tool for assessing fall risk in older people. Based on the performance of five physiological domains (postural sway, hand reaction time, quadriceps strength, proprioception, and edge contrast sensitivity), the PPA computes a fall risk score for each individual and this measure has a 75% predictive accuracy for falls in older people . A PPA z-score of 0-1 indicates mild risk, 1-2 indicates moderate risk, 2-3 indicates high risk, and 3 and above indicates marked risk .
4) Quality of Life
We will evaluate health related quality of life using the EuroQol 5D (EQ-5D) -- a preference-based generic utility instrument that provides weightings for quality adjusted life year (QALYs). QALYs are defined as the benefit of a health intervention in terms of time in a series of quality-weighted health states, in which the quality weights reflect the desirability of living in the state, typically from "perfect" health (weighted 1.0) to dead (weighted 0.0) . QALYs are calculated based on the quality of life of a patient (measured using health utilities) in a given health state and the time spent in that health state. The EQ-5D captures 243 unique health states based on the following domains: 1) mobility; 2) self-care; 3) usual activities; 4) pain and 5) anxiety or depression. We will calculate QALYs using the health state utility values from the EQ-5D to determine if there is a statistically significant difference in the incremental cost per QALY change for participants receiving the aerobic-based training compared with those who are not.
5) Health Resource Utilization
The health resource utilization questionnaire asks participants to report the following visits over a specified time period: 1) health care professionals; 2) admissions or visits to hospital; and 3) laboratory work. The health resource utilization questionnaire has been previously described and supported in previous studies . We will estimate total health care related costs over the 12 months from a Canadian health care system perspective. Participants will be instructed to specify total health care expenditure and report the reason for each item. Additionally, participants will be instructed to report health care expenditure due to any adverse events associated with the aerobic-based training program; this is not anticipated to be a major cost driver. On a per participant basis, costs will be assigned to health care resource utilization using a fully allocated hospital cost model (for in-patient costs) and the British Columbia provincial guide to medical fees (for outpatient costs). Our base case analysis will consider the costs of all health care resource use and our sensitivity analyses will include only intervention related health care resource costs and a complete case analysis.
Aerobic-Based Training (AT) Group
All AT group classes will be led by instructors certified to instruct seniors. Each 60-minute class will include a 10 minute warm-up, a target of 40 minutes of walking, and a 10-minute cool down. Class attendance will be recorded for each participant by the instructors throughout the six-month intervention period.
Over the six month intervention period, we will use three complimentary techniques to monitor and progress exercise intensity of the AT program. Each participant will:
1) Wear a heart rate monitor and will be asked to work initially at approximately 40% of his/her age specific target heart rate (i.e., heart rate reserve; HRR) and gradually progress to reach the target of 60% of HRR. Once the target of 60% of HRR is achieved, it will be sustained by the participant for the remainder of the intervention period;
2) Subjectively monitor the intensity of each workout using the Borg's Rating of Perceived Exertion (RPE) . Participants will be gradually progressed to a target RPE of 14 to 15; and
3) Use the simple "talk" test [50, 51]. Participants will be asked to initially walk at a pace where they can converse comfortably without effort and gradually progress to a pace where conversation requires a bit of effort.
In addition to the formal group classes, all individuals in the AT group will be given a pedometer to serve as both an incentive and reminder to partake in walking on a daily basis. Participants will be asked to record the number of steps each day. All pedometers will be returned to the study coordinator at the 6 month assessment session.
Usual Care (CON) Group
Participants in the CON group will receive educational material about vascular cognitive impairment and about stress management, healthful diet, and smoking. However, this group will not receive specific information regarding physical activity. Participants in the AT group will also be offered these educational materials.
As a primary objective of this study is to provide preliminary evidence of efficacy we will compare participants of the AT group who are compliant with the intervention (defined as attending 60% of the total exercise sessions) to the CON group rather than using an intention-to-treat analysis as would be appropriate in a pivotal clinical trial. In addition, no adjustment for multiple endpoints will be made since in a proof-of-concept study a Type II error is of more concern than a Type I error . For each of the three primary endpoints (i.e., ADAS-Cog, EXIT-25, ADCS-ADL), the change from baseline to six months and 12 months will be assessed using an analysis of covariance model incorporating the baseline measurement. Observing a statistically significant difference on any of the three primary outcomes will be considered preliminary evidence of efficacy.
We will also report variances, co-variances, and effect sizes, as well as sampling feasibility (i.e., ease of recruitment, recruitment rate, withdrawal rate). This information will inform sampling for future trials.