Table 2 Overview of multidomain intervention trials for the prevention of cognitive decline and dementia
Study | Design and population | Multidomain intervention | Primary outcome | Main results |
|---|---|---|---|---|
The MAX trial (Barnes et al., 2013) [11] | N = 126 Adults with cognitive complaints, USA Age, 65+ years Duration, 12 weeks | Individual, home-based mental activity plus class-based physical activity—4 groups 1. Intervention (mental activity + exercise vs. 2. Intervention + control (mental activity intervention + exercise control) vs. 3. Control + intervention (mental activity control + exercise intervention) vs. 4. Control (mental activity + exercise) | Global cognitive change based on a comprehensive neuropsychological test battery | Physical plus mental activity was associated with significant improvements in global cognitive function. |
Alves et al., 2013 [12] | N = 56 Healthy women, Brazil Mean age, 66.8 years Duration, 24 weeks | Creatine supplementation and exercise—4 groups 1. Creatine supplementation vs. 2. Placebo vs. 3. Creatine supplementation + strength training vs. 4. Placebo + strength training | Cognitive function (memory, selective attention, and inhibitory control) | No significant effect on cognition. |
Ihle-Hansen et al., 2014 [13] | N = 195 Patients after the first stroke, Norway Mean age, 71.6 years Duration, 12 months | Outpatient stroke nurse and physician consultation 3 and 6 months post-stroke, information about lifestyle and brain health. Medical treatment optimized. Tailored advice regarding risk factor management and treatment plan sent to a general practitioner. Offered smoking cessation courses vs. care as usual | Trail-making test A and 10-word test from baseline to 12 months follow-up | No difference between the intervention and control groups. |
The SMART study (Fiatarone Singh et al., 2014) [14] | N = 100 Adults with MCI, Australia Mean age, 70.1 years Duration, 18 months | 2 supervised interventions, 2–3 days/week for 6 months with 18 months follow-up - Active OR sham physical training (high-intensity progressive resistance training vs. seated calisthenics) plus - Active OR sham cognitive training (computerized, multidomain cognitive training vs. watching videos/quizzes) | Global cognitive function (ADAS-Cog) and functional independence | Resistance training significantly improved global cognitive function, with the maintenance of executive and global benefits over 18 months. |
Lam et al., 2015 [15] | N = 555 Adults with MCI, Hong Kong Mean age, 75.4 years Duration, 18 months | Physical exercise vs. Cognitive activity vs. Integrated cognitive and physical exercise vs. Social activity (active control) groups | Clinical Dementia Rating sum of boxes (CDR-SOB) scores | No difference between the groups for change in CDR-SOB and functional scores. Integrated physical and cognitive intervention exerted significantly better cognitive benefits on category verbal fluency test but not across all cognitive domains compared to single cognitive or physical activity intervention. |
FINGER (Ngandu et al., 2015) [16] | N = 1260 Persons at-risk of dementia, Finland Age, 60 to 77 years Duration, 2 years | Lifestyle intervention (diet, exercise, cognitive training, vascular risk monitoring) vs. general health advice | Cognition on the neuropsychological test battery | Significant intervention benefit on cognition. |
ASPIS (Matz et al., 2015) [17] | N = 202 Stroke patients, Austria Age, 40 to 80 years Duration, 2 years | Multidomain intervention (clinical therapy, adequate blood pressure, lipid and glycaemic control, healthy diet, regular physical activity, cognitive training) vs. standard stroke care | Cognition on Alzheimer Disease Assessment Scale and neuropsychological test battery | No difference between the intervention and control groups. |
preDIVA (Moll van Charante et al., 2016) [18] | N = 3526 Community-dwelling older persons, the Netherlands Age, 70 to 78 years Duration, 6 years | Multidomain intensive vascular care vs. standard care | Incident dementia and disability score | No difference between the intervention and control groups. |
MAPT (Andrieu et al., 2017) [19] | N = 1680 Community-dwelling older persons, France Mean age, 75.3 years Duration, 3 years | 1. Multidomain intervention + omega-3 supplementation 2. Multidomain intervention + placebo 3. Omega-3 supplementation alone 4. Placebo alone | Cognitive decline on composite Z score | No difference between the intervention and control groups. |
Look AHEAD (Espeland et al., 2018) [20] | N = 1091 Overweight or obese adults with type 2 diabetes, USA Age, 45 to 76 years Duration, 10 years | Lifestyle intervention (diet modification and physical activity) yielding long-term weight loss vs. support and education | Change in cognition (composite measure) | No difference between the intervention and control groups. |
KENKOJISEICH (Bae et al., 2019) [21] | N = 83 Individuals with MCI, Japan Mean age, 76 years Duration, 24 weeks | Physical, cognitive, and social activity sessions vs. health education | Cognition on the National Center for Geriatrics and Gerontology Functional Assessment Tool | Significant intervention effect on spatial working memory. |
Blumenthal et al., 2019 [22] | N = 160 Older adults with cognitive impairment and no dementia, USA Mean age, > 55 years Duration, 6 months | Diet and exercise—4 groups: 1. Aerobic exercise vs. 2. DASH diet nutritional counseling vs. 3. Combination of both aerobic exercise and DASH vs. 4. Health education | Global measure of executive cognitive functioning | The largest improvements were observed for combined aerobic exercise and DASH diet group. |
Body Brain Life for Cognitive Decline (McMaster et al., 2020) [23] | N = 119 Subjective cognitive decline or mild cognitive impairment, Australia Age, 70 to 78 years Duration, 8 weeks | Educational modules covering dementia and lifestyle risk factors, Mediterranean diet, physical activity, and cognitive engagement and additional active components: dietitian sessions, an exercise physiologist session, and online brain training vs. 4 online informational modules to reduce dementia risk | Dementia risk using the Australian National University-Alzheimer’s Disease Risk Index (ANU-ADRI) and cognition | The intervention group showed a significantly lower ANU-ADRI score and a significantly higher cognition score than the control group. |
DO-HEALTH (Bischoff-Ferrari et al., 2020) [24] | N = 2157 Adults having no major health events in the 5 years prior to enrolment, sufficient mobility, and good cognitive status, Europe (Switzerland, France, Germany, Portugal, and Austria) Age, 70 years or older Duration, 3 years | Supplementation and exercise—8 groups: 1. 2000 IU/day of vitamin D3, 1 g/day of omega-3s, and a strength-training exercise program vs. 2. Vitamin D3 and omega-3s vs. 3. Vitamin D3 and exercise vs. 4. Vitamin D3 alone vs. 5. Omega-3s and exercise vs. 6. Omega-3s alone vs. 7. Exercise alone vs. 8. Placebo | 6 primary outcomes: change in systolic and diastolic blood pressure, Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates of non-vertebral fractures and infections | No statistically significant benefits of any intervention individually or in combination for all 6 end points. |