Allard et al. (2017) [40] | 22 participants Age = 72.0 68.2% female MCI (as defined by [61], Clinical Dementia Rating (CDR) < = 0.5, adjusted Mini Mental State Examination (MMSE) 24–30)) | • 20–60 minutes (progressive) • 3 days per week • 24 weeks After first 4–6 weeks, participants include an additional 45–60-minute walk, leading to 4 sessions per week | • Treadmill walking/jogging • Stair stepping • Elliptical training Initially, sessions lasted 20 minutes at 50% Volume of Oxygen (V̇O2) Max; then increased by 5 minutes each week until 40 minutes was reached. Then increased by 5% V̇O2 Max weekly until achieving 70% V̇O2 max. Supervised by trained personnel | • 40 minutes • 3 days per week • 24 weeks Static joint stretching targeted at hamstrings, hip flexors, calves, and chests for 15–30 seconds. Increased number of muscle groups for the first four weeks. | Baseline 6 months V̇O2 Max • Modified Bruce protocol Serum blood derived neurotrophic factor (BDNF) • ELISA | Not reported | No significant differences in V̇O2 max between stretch and aerobic groups. No significant differences in BDNF between stretch and aerobic groups. | No significant difference in V̇O2 max between APOE carriers and non-carriers. Non-carriers in the exercise group showed a significant increase in serum BDNF levels compared to carriers. |
Brown et al. (2021) [41] | 99 participants Age = 69.1 54.6% female Cognitively normal | • 50 minutes • 2 sessions per week • 6 months | • Stationary bike 2 groups: moderate (MI) or high intensity (HI) HI: 10 minute warm up and cool down, main part of the intervention was 11 1-minute intervals at 80% aerobic capacity, broken up by 2 minutes activity recovery. MI: 50–60% aerobic capacity for 50 minutes Intensity determined by Borg Scale of Perceived Exertion and percentage of peak aerobic power, measured via graded exercise test. Percentage of peak aerobic power for 0–3 months calculated using baseline peak aerobic power output; months 4–6 calculated using peak aerobic power output from mid-intervention fitness test Supervised by an Accredited Exercise Physiologist | Information session on the benefits of exercise for physical health and brain benefits. No exercise instructions. | Baseline 3 months (V̇O2 peak, peak power, volume of fat, muscle, bone tissue only) 6 months 18 months Global cognitive function • Digit span • Cogstate one-back • Cogstate identification task • CVLT (learning, short delay recall, long delay recall, and recognition d)` • BVMT (learning and long delay recall) • Cogstate Groton Maze recall • Trails B • Phonemic fluency • Flanker • Set-shifting Attention • Digit span (forward only) • Cogstate identification task Episodic memory • California Verbal Learning Test-II (short delay recall, long delay recall and recognition d`) • Brief Verbal Memory Test long delay recall • Groton maze recall Executive function • Trails B • Phonemic fluency • Flanker • Set-shifting Peak aerobic capacity (V̇O2 peak) • Cycling-based graded exercise test Volume of fat, muscle, and bone tissue (% body fat) • Dual-energy X-ray absorptiometry scan Peak power • Cycling-based graded exercise test | 85.5% in HI and 86.3% in MI (no significant difference) | HI experienced significant improvements in fitness compared to MI and controls. HI experienced significant improvements in peak aerobic power and decreases in % body fat compared to controls. Main effects for time were significant for executive function. Within HI, changes in fitness were associated with changes in global cognitive function and executive function. Increases in fitness associated with improvements in global cognition and executive function in all groups. | No difference between APOE4 carriers and non-carriers on the cognitive composite scores. No interaction between APOE carrier status and fitness change on any cognitive change scores. When stratified by APOE4 carrier status, only APOE4 carriers had an association between improved cardiorespiratory fitness and global cognition. |
Cheng et al. (2014a) [42] | 110 participants Age = 81.5 Dementia MMSE 10–24 Clinical Dementia Rating > = 0.5 | • 60 minutes • 3 sessions per week • 12 weeks | • Tai chi 12 form seated yang style, suitable for frail individuals Intensity not specified Led by research staff | • 60 minutes • 3 sessions per week • 12 weeks Handicraft – participants created shapes by connecting beads | Baseline 3 months 6 months 9 months Primary: • MMSE Secondary: • Forward digit sequence • Backward digit sequence • Backward digit span • Forward digit span • 15-word immediate recall Episodic memory • 30-minute delayed recall Semantic memory • Categorical verbal fluency (animals, fruit and vegetables – 1 minute per category) | Not reported | Mahjong had main effects on MMSE, forward digit span forward digit sequence, and categorical fluency. Tai chi had interactions with MMSE, forward digit span, forward digit sequence, and categorical fluency on time, but no main effects. MMSE was significant better for mahjong and tai chi compared to controls at 6 and 9 months. Mahjong was significantly better than control on forward digit span and forward digit sequence at 6 and 9 months. Tai chi was significantly better on forward digit span at 9 months than controls. Mahjong had a main effect of categorical fluency compared to controls. | Differences between APOE carriers and non-carriers on MMSE, verbal immediate recall and verbal delayed recall |
Cheng et al. (2014b) [43] | 110 participants Age = 81.5 Dementia MMSE 10–24 Clinical Dementia Rating > = 0.5 | • 60 minutes • 3 sessions per week • 12 weeks | • Tai chi 12 form yang style, suitable for frail individuals Intensity not specified Led by research staff | • 60 minutes • 3 sessions per week • 12 weeks Handicraft – participants created shapes by connecting beads | Baseline 3 months 6 months 9 months • Clinical Dementia Rating sum-of-box | Not reported | Baseline 3 months 6 months 9 months Mahjong had an effect with time on CDR sum-of-box. No significant effect of tai chi | Scores on CDR sum-of-box differed between APOE4 carriers and non-carriers |
Eggermont et al. (2009) [44] | 61 participants Age = 84.6 Moderate dementia (MMSE 11–23) | • 30 minutes • 5 sessions per week • 6 weeks | • Hand movement program, including finger movements, pinching a soft ball, handling a rubber ring Intensity not specified Supervised by recreational therapists or students | • 30 minutes • 5 sessions per week • 6 weeks Stories read by the group leader and conversation | Baseline 6 weeks 12 weeks Memory • Face recognition (Rivermead Behavioural Memory Test (RBMT)) • Picture recognition (RMBT) • Eight Words Test measuring Immediate Recall score and Delayed Recall score and Recognition score Executive function • Digit Span Forward and Digit Span Backward (Weschler Memory Scale (WMS) – Revised) • Category fluency • Stop signal task • Attention network task Mood • Geriatric Depression Scale • Symptom Checklist Anxiety Interdaily stability • Actiwatch activity monitor Intradaily variability • Actiwatch activity monitor Relative amplitude • Actiwatch activity monitor | 47/61 attended over 80% of the sessions | No significant results for cognitive, mood, rest-activity domains in intention-to-treat analysis; but in per-protocol analysis mood improved for the exercise group. | No significant effect of APOE carrier status |
Eggermont et al. (2009b) [45] | 97 participants Age = 85.4 81.4% female With moderate dementia (MMSE 11–23) | • 30 minutes • 5 sessions per week • 6 weeks | • Walking at a self-selected speed, with rests as required Intensity not specified Supervised by psychology students | • 30 minutes • 5 sessions per week • 6 weeks Social visits | Baseline 6 weeks 12 weeks Memory • Face recognition (RBMT) • Picture recognition (RBMT) • Delayed recall of the eight words test Executive function • Digit span backwards • Category fluency • Letter fluency Global cognition • Tests not specified | Not reported | No significant results. | No significant impact of APOE carrier status |
Galle et al. (2023) [46] | 102 participants Age = 70.7 75.5% female MMSE > = 25 | • 45 minutes • 7 sessions total • 6 months, with an additional follow-up session at 9 months | • Coaching sessions encouraging daily physical activity: • Walking • Cycling • Housekeeping • Gardening Low-to-moderate intensity encouraged Supervision during coaching sessions | • 45 minutes • 7 sessions total • 6 months Individually guided whole-body muscle stretching sessions | Baseline 24 weeks 36 weeks Physical activity •Number of steps by hip-worn pedometer Self-reported physical activity •Physical activity scale for the elderly Global cognition •15 Word Test delayed recall •Trail Making Test B •Stroop Colour Word Test Interference •Letter Fluency Test •Digit Span backward test Executive function •Trail Making Test AB-ratio •Stroop Colour Word Test Interference •Letter Fluency Test •Digit Span Test backward Verbal episodic memory •Delayed recall condition of the 15-Word Test Short-term memory performance •Location Learning Test •15 Word test Ability to encode and imprint visual information •5 Trials of Location Learning Test Ability to encode and imprint verbal information •5 Trials of the 15 Word Test Learning index •Scores on short-term memory performance tests are standardised and the total number of placement errors on the location learning test inverted Balance, lower body strength, gait speed •Short physical performance battery (SPPB) Handgrip strength •Hydraulic JAMAR dynamometer Muscle strength •SPPB and handgrip strength Aerobic capacity •Six-minute walk test Gait speed •Six-meter walking test Serum concentrations of the cardiovascular risk factor profile •Total cholesterol, HDL- cholesterol, trigylcerides, insulin, and IGF-1 in serum Psychological well-being •Rand-36 mental health sub-scale Depressive symptoms •Centre for Epidemiological Studies Depression Scale Limitations in activities of daily living (ADL) •Katz-15 Frailty (composite) •Number of deficits in activities of daily living, social functioning, emotional well-being and self-reported health | Dropout rates under 25% | Intervention group did significantly more steps per day than controls. Number of ADL limitations decreased in intervention group compared to controls. Mental health score significantly improved in control group. Balance significantly improved in control group. No effect on self-reported physical activity, physical fitness, cognition, frailty, depression, serum concentrations of cardiovascular risk factors. In those who achieved a 35% increase in physical activity, aerobic capacity, number of ADL limitations, gait speed, global cognition, executive function, and verbal memory, compared to those who did not achieve this increase improved. Frailty, mental heath, depressive symptoms, serum concentrations for cardiovascular risk profile, learning, balance, muscle strength, and self-reported level of physical activity were unaffected. | No interaction of APOE4 carrier status for physical activity, cognition function, and physical fitness. APOE4 carrier status moderated learning and verbal memory effects in per protocol analysis. On stratification by APOE4, APOE4 carrier controls showed a relative improvement in performance on the learning index in per protocol analysis. There was greater improvement in executive functioning for APOE4 carriers than non-carriers, in those who achieved more than 35% increase in physical activity compared to those who did not. APOE carrier status did not affect global cognition, learning and verbal memory. On stratification by APOE4 carrier status in participants with a > 35% increase in physical activity there were significant changes on gait speed, global cognition, learning, and verbal memory in APOE4 non-carriers and variance in a smaller group of APOE4 carriers. |
Jensen et al. (2019a) [47] | 198 participants Age = 70.7 42.9% female Clinically diagnosed mild AD (> 19 MMSE) | • 1 hour • 3 sessions per week • 16 weeks First 4 weeks were an adaptation to exercise (focusing on strength 2 sessions/week and aerobic exercise 1 session/week). Following 12 weeks were 3x10 minute aerobic sessions | • Aerobic exercise: • Treadmill • Stationary bike • Cross trainer Moderate-to-high intensity, defined by 70–80% of heart rate reserve (HRR). Heart rate and perceived exertion were monitored. Sessions supervised by an experienced physiotherapist. | • Treatment as usual for the first 16 weeks Post exercise intervention, 4 weeks supervised adaptation exercise for 1 hour, 3 times /week | Baseline 16 weeks Inflammatory markers • Interferon gamma (IFNγ) • Interleukin-10 (IL10) • ILI12p70 • IL13 • IL1β • IL-2 • IL4 • IL6 • IL8 • Tumour necrosis factor alpha (TNFα) • 8-isoprostane • sTREM2 | 83.7% in exercise group | IL6 plasma concentration increased significantly in the exercise group compared to the control group. In ‘high exercise group’ (those with > 80% session attendance and mean intensity of 70% or higher), sTREM2 change in CSF was significantly larger than for controls. Correlations between body mass index (BMI) and relative change in IFNy in CSF and TNFα in plasma. | Plasma IFNγ concentration increased more in controls who were APOE4 carriers compared to APOE4 carriers in the exercise group. There was an increase in sTREM2 in APOE4 carriers in the exercise group and a decrease in controls. |
Jensen et al. (2019b) [48] | 200 participants Age = 69.8 45.3% female Clinical diagnosis of AD (MMSE > = 20) | • 1 hour • 3 sessions per week • 16 weeks First 4 weeks were an adaptation to exercise (focusing on strength 2 sessions/week and aerobic exercise 1 session/week). Following 12 weeks were 3x10 minute aerobic sessions | • Aerobic exercise: • Treadmill • Stationary bike • Cross trainer Moderate-to-high intensity, defined by 70–80% of HRR. Heart rate and perceived exertion were monitored. Sessions supervised by an experienced physiotherapist. | • Treatment as usual for the first 16 weeks Post exercise intervention, 4 weeks supervised adaptation exercise for 1 hour, 3 times /week | Baseline 16 weeks Mental speed and attention • Symbol Digit Modalities Test Behavioural and psychological symptoms • Neuropsychiatric inventory Basic mobility • Timed-up-and-go Gait speed • 10m walk test Walking endurance • Timed 400-meter walk test Dual task performance • Timed 10-meter walk test combined with counting backward from 50 V̇O2 max • Estimated based on workload and average heart rate during the last minute of a 6-minute cycle test, corrected for age and body weight | 83.7% in exercise group | | Exercise group APOE4 carriers maintained performance on mental speed and attention; whereas control APOE4 carriers declined. Improvement in behavioural and psychological symptoms for exercise APOE4 carriers in the exercise groups compared to control APOE4 carriers. Basic mobility improved significantly more from APOE4 carriers than non-carriers. Significant improvements in gait speed and walking endurance in APOE4 carriers (unchanged in non-carriers). Estimated V̇O2 max significantly improved after exercise in APOE4 carriers and non-carriers. |
Karssemeijer et al. (2019) [49] | 115 participants Age = 79.2 46.1% female Mild to moderate dementia (MMSE > = 17) | • 20–40 minutes (progressive increasing by 5 minutes every 2 weeks until 40 minutes is reached) • 3 sessions per week • 12 weeks | • Stationary bike (with or without additional cognitive training) Intensity was measured by 50–60% of HRR from weeks 1–4; 60–70% HRR weeks 5–9. After 12 weeks 65–75% of HRR should be achieved. Used Borg rate of perceived exertion (RPE) for participants on beta blockers. Supervised by trained research assistants | • 30 minutes • 3 sessions per week • 12 weeks Easy relaxation and flexibility exercises | Baseline 6 weeks (executive function tests except letter fluency and all psychomotor speed tests) 12 weeks 24 weeks Executive functioning • Short form of Trail Making Test Part B • Abbreviated 5-line Stroop Colour Word Test interference score • Letter fluency • Rule Shift Cards Episodic memory • Location Learning Test-Revised Working memory • WAIS (Weschler Adult Intelligence Scale)-III Digit Span • WMS-III Spatial Span Psychomotor speed • Short form of Trail Making Test part A • Abbreviated Stroop Colour Word Test parts I and II | 81.1% (aerobic group) and 87.3% exergame (aerobic + cognitive stimulation group) | No significant differences between exergame, aerobic group and control group on executive function, episodic memory or working memory. Significant improvement in psychomotor speed in aerobic and aerobic and cognitive groups compared to controls at 12 weeks. | Carrying APOE4 did not influence the relationship between training and cognitive performance. |
Lautenschlager et al. (2008) [50] | 170 participants Age = 68.7 50.6% female Memory problems but no formal diagnosis (> 19 on Telephone Interview for Cognitive Status-Modified; MMSE > 24) | • 50 minutes • 3 sessions per week (though some flexibility as aiming for 150 minutes per week total) • 24 weeks Participants already achieving 150 minutes per week were encouraged to carry out an additional 50-minute session | • Most frequently recommended walking but other types of exercise were accepted Received a behavioural intervention incorporating a personalised program workbook Moderate intensity Supervised during interview | Educational material about memory loss, stress management, healthful diet, alcohol consumption, and smoking not physical activity. Materials offered to intervention group. | Baseline 6 months 12 months 18 months Physical activity • Community Healthy Activities Program for Seniors survey • Pedometer • Diary of activity • Alzheimer Disease Assessment Scale (ADAS- Cog) • CDR sum-of-box • Cognitive Battery of the Consortium to Establish a Registry for Alzheimer Disease total number of words recalled with and without delay • Digit Symbol Coding Test Verbal fluency • Number of words beginning with F, A, or S in one minute measured by the Delis-Kaplin Executive Function Battery Premorbid Intelligence Quotient • Cambridge contextual reading test Frequency and severity of depressive symptoms • Beck Depression inventory Quality of life • Medical outcomes 36-item short-form health survey physical and mental composite scores | 78.2% | Exercise group had significantly better ADAS-Cog scores, physical activity levels, and delayed recall than control group. | APOE4 non-carriers in the intervention group had significantly better ADAS-Cog than other groups combined and APOE4 carriers and non-carriers in the control group. |
Legault et al. (2011) [51] | 73 participants Age = 76.5 50.3% female At risk for cognitive decline, but no MCI (telephone interview for cognitive status > 31). | • Target of 150 minutes/week, including two 60-minute centre-based training sessions per week • Four months • 8 visits per month Tailored home-based walking sessions at 1–2 per week for first month. Encouraged to increase duration, speed, and frequency, to reach 150 minute/week goal. | • Primarily walking • Other endurance activities (e.g., stationary cycling) were used when participants could not walk • Centre-based sessions were 40 minutes walking stimulus and 20 minutes flexibility training Intensity not specified Supervised during centre-based sessions | • Weekly Healthy Aging Education intervention – lectures based on health education. Topics included medication, foot care, travelling and nutrition. | Baseline Two months (executive function only) Four months Executive function • Self-Ordered Pointing Task • 1-Back and 2-Back tests • Eriksen flanker task • Task Switching test • Trail Making Test Part A and B Episodic memory • Hopkins Verbal Learning Test immediate recall and delayed recall • Logical Memory task from Wechsler Memory Scale-III parts I and II Global cognition • Composite of tests of executive function and episodic memory | Attendance worst in physical activity group (76%). | No significant improvements in overall composite scores or executive function and episodic memory. | APOE4 carrier status had no effect on outcomes. |
Sanders et al. (2020) [52] | 91 participants Age = 82.3 64.8% female All-cause dementia (MMSE > 10) | • 3 sessions per week • 24 weeks (12 weeks low intensity (LI), 12 weeks HI | • Walking (outdoors or indoors if weather unsuitable) • Lower limb strength training program For walking sessions, intensity determined by heart rate wrist band (percentage of Heart Rate max (HRmax)) and by observer-determined Borg RPE. LI – perceived exertion 9–11 and target HR 57–63% HRmax; HI alternating 4-min peak performance at perceived exertion 15–16 and 83–89% HRmax with 3-min active rest at perceived exertion 13–14 and 71–77% HRmax. For strength sessions intensity determined subjectively with observer-determined perceived exertion (LI 9–11; HI 13–16). 0.5kg ankle weights added for all exercises except toe stands in HI phase. One-to-one supervision by a trained research assistant | Flexibility exercises with no weights and recreational activities (board games or social visits depending on preference) | Baseline 12 weeks 24 weeks At 6, 18, and 36 weeks STROOP, leg strength and 6-meter walk speed only Endurance • 6-minute walk test Lower body strength and functional mobility • SPPB Habitual gait speed • 6-meter walking speed test Balance • FICSIT-4 Quadriso table • Lower body muscle strength Functional mobility • Timed up and go Global cognition • MMSE Psychomotor speed • Trail Making Test A Verbal memory span • Digit Span Forward Verbal working memory • Digit Span Backward Visual memory span • Visual Memory Span Forward Visual working memory • Visual Memory Span Backward Attentional processing and inhibitory control • STROOP Executive function • Phonemic fluency | Mean attendance was ~ 60% for exercise group. | Habitual gait speed was significantly positively improved by the intervention compared to control at 18 and 24 weeks. No significant effects on other physical or cognitive measures. | APOE carrier status did not moderate the effects of exercise on physical or cognitive function. |
Sindi et al. (2021) [53] | 756 participants Age = 69.2 46.6% female Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) > 6 and either word list memory task < = 19; word list recall < = 75%; MMSE < = 26 | • 30–60 minutes (progressive) • 3–8 sessions per week (progressive) • Two years | Individually tailored, progressive muscle strength training and aerobic exercise programs • Strength: targets eight muscle groups • Aerobic: Nordic walking, aqua gym, jogging, gymnastics Intensity not specified Supervised by study physiotherapists | Regular health advice according to established guidelines | Baseline Two years Relative leukocyte telomere length (LTL) • DNA extracted from peripheral blood Cognition • Neuropsychological Test Battery (NTB) extended version, total and domain scores for memory, long-term memory, processing speed, and executive function | ~ 60% attended > 50% of physical activity sessions [143] | No significant differences between intervention and control groups for LTL maintenance Cognitive benefits more pronounced in participants with LTL maintenance. Effect of the intervention on executive function and long-term memory were clearer with increasing relative LTL. | Better LTL maintenance among APOE4 carriers than non-carriers. |
Solomon et al. (2018) [54] | 1109 participants Age = 69.3 46.3% female CAIDE > 6 and either word list memory task < = 19; word list recall < = 75%; MMSE < = 26 | • 30–60 minutes (progressive) • 3–8 sessions per week (progressive) • Two years | Individually tailored, progressive muscle strength training and aerobic exercise programs • Strength: targets eight muscle groups • Aerobic: Nordic walking, aqua gym, jogging, gymnastics Intensity not specified Supervised by study physiotherapists | Regular health advice according to established guidelines | Baseline 12 months 24 months Cognitive performance • NTB total score Executive function (NTB) • Category Fluency • Digit Span • Concept Shifting Test (condition C) • Trail Making Test (shifting score B-A) • Shortened 40-stimulus version of the original Stroop test (interference score 3 − 2) Processing speed • Letter Digit Substitution • Concept Shifting (condition A) • Stroop (condition 2) Memory • Visual Paired Associates, immediate and delayed recall • Logical Memory immediate and delayed recall • Word List Learning and Delayed recall Abbreviated memory (post-hoc) • 2 associative memory and 2 logical memory tests | ~ 60% attended > 50% of physical activity sessions [143] | | No significant difference in the effect of intervention between APOE4 carriers and non-carriers. NTB total score and abbreviated memory changed significantly annually for APOE4 carriers, but not non-carriers. In ‘best-fitting models’, NTB total score and memory improved less in APOE4 carriers than non-carriers. |
Solomon et al. (2021) [55] | 1260 participants Age = 69.4 46.7% female CAIDE > 6 and either word list memory task < = 19; word list recall < = 75%; MMSE < = 26 | • 30–60 minutes (progressive) • 3–8 sessions per week (progressive) • Two years | Individually tailored, progressive muscle strength training and aerobic exercise programs • Strength: targets eight muscle groups • Aerobic: Nordic walking, aqua gym, jogging, gymnastics Intensity not specified Supervised by study physiotherapists | Regular health advice according to established guidelines | Baseline 12 months 2 years • CAIDE dementia score | ~ 60% attended > 50% of physical activity sessions [143] | CAIDE score significantly decreased for intervention group compared to controls. | No significant differences by APOE carrier status. |
Stern et al. (2019) [56] | 132 participants Age = 40.5 70.5% female Cognitively normal | • 40–55 minutes (10–15 minutes warm up/cool down and 30–40 minutes of exercise) • 4 sessions per week • 24 weeks | • Aerobic exercise in a Fitness Centre selected from a series of aerobic activities Intensity at weeks 1 and 2 set at 55–65% HRmax (determined by a qualifying aerobic capacity test); weeks 3 and 4 65–75% HRmax; weeks 5–26 75% HRmax; Contacted by coaches on a weekly basis to monitor progress | Stretch/tone to improve flexibility and core strength targeting all major muscle groups. | Baseline 12 weeks (except imaging) 24 weeks Aerobic capacity/ V̇O2 max • Graded exercise test on an electronic-braked cycle ergometer Executive function • Set switching (letter classification and digit classification) • CogState Groton Maze Learning Test Episodic memory • Modified Rey Auditory Verbal Learning Test • CogState Continuous paired associate learning Processing speed • Digit symbol (WAIS)-III digit symbol subtest) • Cogstate Groton Maze Chase Test • Cogstate Identification Task Language • Controlled Oral Word Association Test • Animal naming Attention • The 2 and 7 test Working memory • WAIS-III letter-number sequencing • Cogstate N-back Everyday function • Timed instrumental ADL tasks • BMI Cortical thickness • T1-weighted magnetisation-prepared rapid gradient echo scan | 33.33% attrition rate for exercise group | V̇O2 max significantly increased in intervention at 12 and 24 weeks compared to controls. Executive function in intervention group significantly improved at 24 weeks; but no changes on other cognitive outcomes. No effect of exercise intervention on Timed Instrumental ADL. Significant effect on aerobic intervention on BMI after 24 weeks. Intervention was associated with significantly increased cortical thickness in left caudal middle frontal cortex Brodmann area. | APOE4 carriers showed less improvement in executive function with aerobic exercise than non-carriers. No difference in other cognitive areas. |
Stonnington et al. (2020) [57] | 53 participants Age = 63.4 100% female Cognitively normal (MMSE > 28) | • 60 minutes (first 5 minutes warm up and last 5 minutes cool down) • At least 40 sessions over 6 months | • Zumba: dance and aerobic movements, including samba, salsa, merengue, mamo, hip-hop, squats, or lunges, to music. Supervised by Zumba instructors. | Maintenance of habitual exercise | Baseline 3 months 6 months Visuospatial working memory, error monitoring, information processing speed, short-term delayed recall for a complex hidden maze • Groton maze learning test Visual recognition memory and learning • One-card learning Working memory, attention • Two-back test Impulsivity, inhibition • Set-shifting Visual learning and memory • Continuous paired associate learning Executive functioning • Delis-Kaplan Executive Functioning System Colour-Word Interference Test • Delis-Kaplan Executive Functioning System Sorting Test Visual attention, task-switching • Trail-making Test parts A and B Verbal memory • Rey’s Auditory Verbal Learning Test long-term memory score Quality of life • Short Form Health Survey (SF-36) Kcal/wk total exercise and kcal/wk moderate intensity • Community Healthy Activities Model Program for Seniors • Body weight and height Aerobic fitness • 6-minute walk test (baseline only) Enjoyment of Zumba, ability to follow dance moves, and the feeling that it was a good work-out (intervention group only – weekly) • Ordinal scale | Median number of sessions per week attended was 2 in intervention group | No significant differences at any time point between groups in physical exercise, BMI, and neuropsychological test scores. At 3 months, change in weight and quality of life were significantly different between groups, but not at 6 months. Percentage of participants with more than a 0.5SD improvement in Groton maze learning test total errors and Delis Kaplan executive functioning system color-word score at 6 months or last follow up was significantly higher in the intervention group than the control group. | No APOE carrier status interaction. |
Uijen et al. (2020) [58] | 101 participants Age = 79.8 46% female Mild to moderate dementia (MMSE > = 17) | • 20–40 minutes (progressive increasing by 5 minutes every 2 weeks) • 3 sessions per week • 12 weeks | • Stationary bike (with or without additional cognitive training) Intensity was measured by 50–60% of HRR from weeks 1–4; 60–70% HRR weeks 5–9. After 12 weeks 65–75% of HRR should be achieved. Used Borg RPE for participants on beta blockers. Supervised by trained students or research assistants | • 30 minutes • 3 sessions per week • 12 weeks Easy relaxation and flexibility exercises | Baseline 6 weeks (executive function tests except letter fluency and all psychomotor speed tests) 12 weeks 24 weeks Executive function • Trail Making Test part B • Stroop Colour Word Test card III • Letter fluency • Rule Shift Cards Test from the Behavioural Assessment of the Dysexecutive Syndrome Episodic memory • Location learning test-revised Working memory • WAIS-III digit span • WMS-III spatial span Processing speed • Trail Making Test part A • Stroop Colour Word Test cards parts I and II | 14 participants did not complete the study | Compared to controls, 4.5% improved significantly on global cognition; 13.4% on executive function; 14.9% on processing speed; 6% on episodic memory; 4.5% working memory. | No significant interactions with APOE carrier status. |
Vidoni et al. (2021) [59] | 117 participants Age = 72.9 66% female No cognitive impairment but elevated or subthreshold cerebral amyloid levels | • No more than 50 minutes • 3–5 sessions per week • 52 weeks Started with an aim of 60 total minutes of exercise in week 1 which increased by 21 min/week until 150 min/week of aerobic exercise was achieved | • Aerobic exercise (primarily walking) but allowed other forms to avoid boredom Intensity set as target heart rate zone (40–55% of HRR to start, then increased by 10% of HRR every 3 months) Supervised by certified personal trainers for the first 6 weeks of exercise and at least once/week after this time | Education control, provided with public health information about exercise and on completion of the study received membership to a community gym | Baseline Week 26 (except V̇O2 max or MRI) Week 52 Global amyloid burden • 18F – AV45 PET scan standard uptake value ratio Hippocampal volume & total grey matter volume • Siemans 3.0 Tesla Skyra scanner Executive function • Verbal fluency (sum of animals and vegetables) • Trail making test B • Digit symbol substitution test • Interference portion of Stroop Verbal memory • Immediate and delayed portions of the logical memory test • Sum of free recall trials of the selective reminding test Visuospatial domain • Block Design • Space relations • Paper folding test • Hidden pictures • Identical pictures Cardiorespiratory fitness testing : V̇O2 max • Graded maximal exercise test | Participants completed an average of 84.6% minutes of the exercise sessions | Aerobic exercise group significantly improved cardiorespiratory fitness, but no differences in global amyloid burden, brain volume, or cognitive performance compared to controls. | No differences by APOE carrier status. |
Yu et al. (2022) [60] | 26 participants Age = 77.6 35.6% female Mild-to-moderate AD (MMSE 15–26; Clinical dementia rating 0.5-2) | • 20–50 minutes • 3 sessions per week • 6 months | • Stationary cycling Intensity gradually increased from 50–55% HRR or rate of perceived exertion 9–11 for 20–30 minutes to 70–75% HRR or rate of perceived exertion 12–14. Increases in intensity were alternated with session duration (5-minute increases and 5% intensity/1 point perceived exertion increases) Supervised | • Matched to exercise group Seated movements at static stretching at low intensity (< 20% HRR or < 9 rate of perceived exertion) | Baseline 3 months 6 months Feasibility • Recruitment rate, retention rate, and blood collection rate Plasma t-tau, p-tau181 and plasma Ab42/40 ratio • Simoa assays | 84.8% of exercise sessions were attended. | No significant interactions between groups and time for the biomarkers. | APOE e2/e4 had a significantly lower t-tau level than APOE e3/e4 |