Physical activity and cognitive function in individuals over 60 years of age: a systematic review

Figures & data

Table 1 Characteristics of included studies

Parameters	Number of studies	References
Type of included studies
Randomized controlled trial	10	^Citation8^–^Citation10,Citation17^–^Citation21,Citation26,Citation27
Prospective cohort	15	^Citation11^–^Citation16,Citation22^–^Citation24,Citation55^–^Citation60
Case-control	1	^Citation61
Observational	1	^Citation62
Overall quality of included studies
Good	9	^Citation9,Citation10,Citation14,Citation17^–^Citation22
Fair	15	^Citation8,Citation11^–^Citation13,Citation15,Citation23,Citation26,Citation27, ^Citation55^–^Citation58,Citation60^–^Citation62
Poor	3	^Citation16,Citation24,Citation59
Overall risk of bias in included studies
Low	8	^Citation9,Citation10,Citation14,Citation17,Citation18,Citation20^–^Citation22
Moderate	16	^Citation8,Citation11^–^Citation13,Citation15,Citation19,Citation23,Citation26, ^Citation27,Citation55^–^Citation58,Citation60^–^Citation62
High	3	^Citation16,Citation24,Citation59

Table 2 Design, methods, interventions and assessment, and outcome measures in included studies

Source and study design	Methods	Participants	Interventions	Cognitive function measurements
Buchman et al^Citation22 Prospective study	Total daily physical activity was measured with actigraphs at baseline. Late-life physical, social, and cognitive activities were assessed by self-report and by the 1985 National Health Interview Survey questions at baseline and follow-up. Follow-up: annual assessment for 3.5±1.54 years	716 subjects 114 males and 602 females 81.6±7.12 years Inclusion criteria: eligible participants of Rush Memory and Aging Project. Exclusion criteria: Presence of clinical AD dementia and non-AD dementia; unable to have at least one follow-up cognitive testing	None	A computer-scoring battery of 19 tests Diagnosis of AD and non-AD was performed by clinicians using National Institute of Neurological and Communicative Disorders, Stroke-Alzheimer’s Disease and Related Disorders Association Criteria
Busse et al^Citation17 RCT	Participants were randomized to a control group (n=14) or a treatment group (n=17). Cognitive status was assessed at baseline and follow-up using a neurocognitive test battery. Neither the participants nor the outcome assessors were blinded, and the use of allocation concealment is unclear. Follow-up: 3, 6, and 9 months	31 subjects 8 males and 23 females 62–86 years Inclusion criteria: No programmed physical exercise 6 months prior to selection; subjective memory complaints; normal GDS and MMSE; changes in objective memory test; preserved function in instrumental and basic activities of daily living. Exclusion criteria: dementia, depression, anxiety disorders, head trauma or stroke within one year, substance abuse, unstable cardiovascular disease	Treatment group: a one-hour biweekly training session for 9 months with 6 resistance-training exercises per session. Loads progressively increased in series of 12, 10, and 8 repetitions. Control group: no intervention	Rivermead Behavioral Memory Test Wechsler Adult Intelligence Scale Direct and Indirect Digit Span Memory Complaints Scale Cambridge Cognitive Test
Bixby et al^Citation62 Observational	Participants were recruited from a retirement community through posted flyers, closed-circuit television announcements, and investigator presentations. Physical activity levels were assessed using the YPAS. Cognitive and inhibitory executive function was assessed by the Stroop Color and Word Test. Follow-up: not applicable	120 subjects 38 males and 82 females 65–92 years Retirement community residents recruited through posted flyers, closed-circuit television announcements, and investigator presentations. Inclusion criteria: above average intelligence; stable patterns of physical activity during a 3–5-year period before the study. Exclusion criteria: depression, dementia	None Physical fitness assessment: YPAS and weekly energy expenditure (beyond basal metabolic rate). Stability in physical activity levels for 3–5 years prior to the study assessment: a health history questionnaire. Cognitive function assessment: Kaufman Brief Intelligence Test and Stroop Color and Word Test	Kaufman Brief Intelligence Test Stroop Color and word Test
Cassilhas et al^Citation18 RCT	Participants were randomized to 3 groups: a control group (n=23), moderate exercise group (n=19), and high exercise group (n=20). Use of blinding and allocation concealment in the study is unclear. Physical fitness was assessed at baseline and follow-up by the one RM test. Cognitive status was assessed at baseline and follow-up using a neuropsychological test battery. Follow-up: 24 weeks	62 subjects All males 65–75 years Inclusion criteria: not described. Exclusion criteria: cardiovascular disease; psychiatric conditions; use of psychotropic drugs; <8 years of schooling; dementia (MMSE score <23)	Moderate exercise group: Three one-hour sessions/week (10-minute cycling warm-up, stretching exercises and weight training using loads of 50% of one RM and alternating segments with two series of 8 repetitions for each segment). High exercise group: Three one-hour sessions/week (10-minute cycling warm-up, stretching exercises, and weight training using loads of 80% of one RM and alternating segments with two series of 8 repetitions for each segment). Control group: one weekly training session consisting of warm-up and stretching exercises, but no overload training	Wechsler Adult Intelligence Scale III Wechsler Memory Scale-Revised Toulouse-Pieron concentration attention test Ray-Osterrieth complex figure
Geda et al^Citation61 Case-control	Participants underwent stratified random sampling in to case or control group. Physical fitness was assessed through self-reporting at baseline. Cognitive status was assessed at baseline and follow-up using a neuropsychological test battery and visuospatial skills. Follow-up: 4 years	1,324 subjects 681 males and 633 females 70–89 years Participants of the Mayo Clinic Study of Aging Cases: (n=198) cases with mild cognitive impairment based on: concern expressed by a physician or nurse; cognitive impairment in one or more tested domains; ability to participate in normal functioning activities; and free of dementia. Controls: (n=1,126) cases with normal cognitive function according to published normative criteria for the community	None Physical fitness assessment: a self-reported questionnaire derived from the 1985 National Health Interview Survey and the Minnesota Heart Survey intensity codes. Cognitive function assessment: Mayo Clinic criteria for mild cognitive impairment	Mayo Clinic criteria for mild cognitive impairment
Klusmann et al^Citation10 RCT	This study enrolled German-speaking women from Berlin. Eligible subjects were randomized into 2 intervention groups (n=91 for exercise group, n=92 for computer group), and a control group (n=76). 12 participants (5 in the exercise group and 7 in the computer group) refused to participate after being informed about their group assignment and withdrew consent before treatment started. A complete neuropsychological assessment and physical evaluation at baseline and 6 months. Follow-up: 6 months	259 subjects All female Age >70 years Eligibility criteria: being unfamiliar with the computer and exercising less than one hour per week. Exclusion criteria: severe visual or hearing impairment; a previous or current diagnosis of depression or psychosis; any other neurological or medical disorder that would interfere with cognitive performance or preclude successful participation in the intervention programs	Exercise group: exercise program consisted of aerobic endurance, strength, and flexibility training, as well as practice of balance and coordination. Computer group: heterogeneous and multifaceted themes including creative matters, coordinative and memory tasks, eg, operating with the common software and hardware, writing, playing, calculating, surfing on the Internet, emailing, drawing, image editing, and videotaping. Control group: continued their habitual life	Neuropsychological assessment RBMT, FCSRT, TMT, and Stroop Test
Ku et al^Citation11 Prospective study	Physical activity and activities of daily living were assessed through questionnaires. The survey was conducted every 3–4 years from 1996 to 2007. Cognitive performance was assessed using the 10-item SPMSQ. Follow-up: 11 years	1,160 subjects 586 males and 574 females, ≥67 years Inclusion criteria: participants of the longitudinal Survey of Health and Living Status of the Elderly (Taiwan Department of Health) aged ≥67 years. Exclusion criteria: not stated	None Physical activity assessment: questionnaire survey at baseline. Cognitive performance assessment: SPMSQ that was validated for the Chinese version of the MMSE	Ten-item SPMSQ
Larson et al^Citation55 Prospective study	The current study was to examine the temporal relationship of physical exercise preceding development of dementia. Physical activity was assessed at baseline by an interview. Cognitive function was assessed at baseline and follow-up using the CASI. Follow-up: biennially for 6.2 years	1,740 subjects 693 males and 1,047 females, ≥65 years Participants of the ACT study Inclusion criteria: ACT study participant with CASI score above the 25th percentile; residing in the Seattle area at time of study. Exclusion criteria: pre-existing dementia or cognitive impairment	None Physical exercise assessment: subject interview (number of days per week and number of hours per session) during the past year. Participants who exercised at least 3 times a week were classified as regular exercisers. Cognitive status and incident dementia assessment: CASI	CASI (score <86 resulted in a neuropsychological clinical evaluation) DSM-IV criteria for dementia (25 criteria in total)
Laurin et al^Citation12 Prospective study	Physical activity and cognitive status were assessed at baseline and follow-up. Follow-up: 5 years	4,615 subjects 1,831 males and 2,784 females, ≥65 years Participants of the 1991–1992 Canadian Study of Health and Aging, a prospective cohort study of dementia. Inclusion criteria: age ≥65 years and registered in the 1991–1992 Canadian Study of Health and Aging. Exclusion criteria: dementia	None Physical fitness assessment: a self-administered questionnaire by mail. Cognitive function assessment: 3MS	3MS score (a reduction of ≥5 points indicative of cognitive decline)
Lytle et al^Citation13 Prospective study	Physical activity was assessed at baseline through self-reporting and cognitive function was assessed at baseline and at follow-up using the MMSE. Follow-up: 2 years	1,146 participants 722 males versus 424 females, ≥65 years Participants of MoVIES Inclusion criteria: Residing in the community of Monongahela Valley (not in a skilled care facility) at time of recruitment; fluent in English and having at least a 6th grade education. Exclusion criteria: not described	None Physical activity assessment: a standardized questionnaire. Exercise was classified as aerobic (high level) or anaerobic (low level). Cognitive status assessment: MMSE	MMSE score (drop of at least 3 points between assessments was indicative of cognitive decline)
Middleton et al^Citation14 Prospective study	Physical fitness was assessed at baseline and follow-up by using a battery of fitness and metabolism tests, and cognitive function was assessed at baseline and follow-up by using the 3MS. Follow-up: 2 or 5 years	197 subjects Sex not stated 70–79 years Participants of the Health ABC study. Inclusion criteria: ability to walk 0.4 km, climb ten stairs, and perform basic activities of daily living without difficulty; no plans to leave the area for the next 3 years. Exclusion criteria: life-threatening illness; mobility limitations; cognitive impairment (3MS score <80)	None Physical fitness assessment: doubly-labeled water techniques for total energy expenditure measurement between baseline and follow-up; a respiratory gas analyzer for measuring resting metabolic rate; an interviewer-administered questionnaire at first visit to ascertain physical activity habits over the past 7 days. Cognitive status assessment: 3MS score	3MS score (a decline of at least one standard deviation or 9 points from baseline to the most recent follow-up visit indicated cognitive decline)
Miu et al^Citation9 RCT	Participants were randomized to a control group (n=49) or a physical activity treatment group (n=36). Physical fitness was assessed at baseline and follow-up by using a battery of physical function tests. Cognitive status was assessed at baseline and follow-up using the MMSE and the ADAS-Cog. Follow-up: 3, 6, 9, and 12 months	85 participants Sex not clearly stated ≥65 years Participants of the memory clinic at a regional hospital in Hong Kong Inclusion criteria: mild-to-moderate dementia; MMSE 10–26; age >60 years; community-dwelling; ambulatory, having a caregiver willing to participate and escort the patient to the hospital for training and assessment. Exclusion criteria: severe dementia or MMSE score <10	Treatment group: aerobic exercise training supervised by a physiotherapist, including treadmill, bicycle, and arm ergometry, and 10-minute flexibility training prior to each session. Training sessions occurred biweekly and lasted 45–60 minutes each. Total duration of treatment was 3 months. Control group: no intervention	MMSE ADAS-Cog
Mortimer et al^Citation19 RCT	Participants were randomized into 4 groups: group 1, Tai Chi (n=30); group 2, walking (n=30); group 3, social (n=30); and group 4, no intervention (n=30) for a total of 40 weeks.	120 subjects 40 males and 80 females 60–79 years Inclusion criteria: participants of Jingansi Temple Community of Shanghai, China aged 60–79 years. Exclusion criteria: history of stroke, Parkinson’s disease, or other neurological disease; inability to walk unassisted for 2 km or maintain balance with feet side-by-side or semi-tandem for 10 seconds each; education-adjusted Chinese MMSE <26; cardiovascular disease; musculoskeletal conditions; contraindication for MRI; unable to participate in the full study and regular vigorous exercise or Tai Chi practice	Tai Chi: practising 3 times per week (20 minutes warm-up, 30 minutes of Tai Chi practice, and 10 minutes cool-down). Walking: a 400 m circular walking (10 minutes of warm-up, 30 minutes of brisk walking, and 10 minutes of cool-down exercise). Social interaction: meeting with group leader for one hour 3 times per week. Brain volume assessment: MRI at baseline and at the end of intervention (40 weeks). Cognitive assessment: neuropsychological battery at baseline, 20 weeks, and 40 weeks	Brain volume using MRI Neuropsychological battery test
Muscari et al^Citation20 RCT	Subjects were randomized into a control group (n=60) and a physical activity treatment group (n=60). Cognitive status was assessed at baseline and follow-up by using the MMSE. Follow-up: 12 months	120 subjects 62 males and 58 females 65–74 years Inclusion criteria: participants of the Pianoro Study, aged 65–74 years. Exclusion criteria: Presence of any cardiovascular disease and the followings; MMSE score <24; BMI <18 or >32; systolic BP >180 or <110 mmHg; diastolic BP <110 mmHg; malignancy; moderate or severe respiratory insufficiency; severe arthrosis; recent fractures, palsy or relevant neuromotor deficits; hemoglobin <11 g/dL; aortic aneurysm >3.5 cm	Treatment group: 12 months of 3 one hour-long sessions per week of supervised endurance exercise training in a community group. Control group: education to improve lifestyle and self-administered programs to increase physical activity	MMSE score (decrease of greater than one point was indicative of cognitive decline)
Nagamatsu et al^Citation26 RCT	Subjects were randomized, single-blinded into: twice-weekly resistant training (n=28); twice-weekly aerobic training (n=30); or twice-weekly balance and tone training (control) group (n=28). Follow-up: 6 months	86 subjects All females 70–80 years Inclusion criteria: female, aged 70–80 years, with probable mild cognitive impairment. Exclusion criteria: not described	Resistant training group: a Keiser pressurized air system and free weights were used. Aerobic training group: an outdoor walking program. Balance and tone training (control) group: stretching, range of motion, balance exercises, and relaxation technique	Primary outcome measure: Stroop Test performance Secondary outcome measures: TMT, Verbal Digits Test Memorizing face-scene pairs Everyday Problem Test
Nguyen et al^Citation27 RCT	Participants were randomly divided into 2 groups; Tai Chi (n=48) and control (n=48) group. Experienced Tai Chi instructors were selected by investigators to teach classes. Outcome measures were assessed at baseline and the end of 6-month Tai Chi training. Follow-up: 6 months	102 subjects 48 males and 48 males 60–79 years Inclusion criteria: MMSE score >25; having no experience in Tai Chi. Exclusion criteria: serious diseases such as symptomatic coronary diseases, angina, arrhythmia, orthostatic hypotension, and dementia	Treatment group: a 60-minute Tai Chi session twice a week for 6 months. The session consisted of a 15-minute warm-up and cool-down period. Control group: no intervention, maintained daily routine activities and not to begin any new exercise program	TMT for motor speed and visual attention
Podewils et al^Citation56 Prospective study	Physical activity information was assessed at baseline and follow-up by interview and the 3MS, respectively. Follow-up: annually for 5.4 years	3,375 subjects 1,350 males and 2,025 females ≥65 years Inclusion criteria: enrollment in Cardiovascular Health Cognition Study; residing in Sacramento County, CA, Washington County, MD, Forsyth County, NC, or Pittsburgh, PA, USA. Exclusion criteria: dementia	None Physical activity assessment: modified Minnesota Leisure Time Activity Questionnaire. Cognitive status assessment: 3MS or the Telephone Interview for Cognitive Status for participants who did not receive a clinical evaluation	3MS score (<80 within the last 2 visits; decline of at least 5 points within the follow-up period; Telephone Interview for Cognitive Status score of <28; diagnosis of dementia that was documented in medical records
Ravaglia et al^Citation23 Prospective study	Physical activity was self-reported at baseline by using a questionnaire and cognitive status was measured at baseline and follow-up by using a neuropsychological test battery. Participants were screened for incident dementia using an extensive neuropsychological test battery. Follow-up: 4 years	749 subjects 348 males and 401 females, ≥65 years Inclusion criteria: individuals ≥65 years in the Conselice Study of Brain Ageing. Exclusion criteria: per the Conselice Study of Brain Ageing	None Physical fitness assessment: Paffenbarger Physical Activity Questionnaire. Cognitive status assessment: GDS, MMSE, and MDB for use in rural and poorly educated subjects	MMSE (cognitive impairment defined as a score of <24) MDB
Scarmeas et al^Citation57 Prospective study	Physical activity was self-reported at baseline, and cases of incident dementia were identified at each follow-up using a neuropsychological test battery in conjunction a consensus diagnosis among an expert panel based on the DSM-IV criteria. Follow-up: every 1.5 years for 15 years	1,880 participants 587 males and 1,293 females 70–82 years Participants were recruited through the WHICAP from a sample of Medicare beneficiaries in northern Manhattan. Inclusion criteria: WHICAP participants. Exclusion criteria: not described	None Physical activity assessment: two versions of the Godin leisure time exercise questionnaire. Cognitive status assessment: a neuropsychological test battery testing the domains of memory, language, reasoning, processing speed, and visual-spatial ability	The decision of expert panel composed of neurologists and neuropsychologists in according to DSM-IV criteria
Schuit et al^Citation24 Prospective study	Physical activity was assessed at baseline through self reporting. Cognitive function was assessed at baseline and follow-up using the MMSE. Follow-up: 3 years	347 participants All males 70–80 years Inclusion criteria: participants of the Zutphen Elderly Study, the Netherlands. Exclusion criteria: per the Zutphen Elderly Study	None Physical fitness assessment: a self-administered questionnaire at baseline. Physical activity was categorized as either “maximal 1 hour/day” or “more than 1 hour/day”. Cognitive status assessment: MMSE at baseline and follow-up	MMSE (drop in 3 points indicative of cognitive decline)
Smiley-Oyen et al^Citation21 RCT	Participants were randomized to an aerobic physical activity (Cardio, n=28) group or a strength-and-flexibility (Flex-Tone, n=29) training group. Physical fitness was assessed at baseline and follow-up using a battery of fitness tests, and cognitive status was assessed at baseline and follow-up by using a battery of neurocognitive tests. Follow-up: at 4 and 10 months	62 subjects 16 males and 41 females 65–79 years Residents of the mid-western US Inclusion criteria: living independently; able to exercise safely. Exclusion criteria: various health-related reasons (autoimmune disease, cancer diagnosis within the previous 5 years, or conditions which may be exacerbated by strenuous exercise); being “too-fit” (participation in exercise >3 times/week at >40% of their heart rate reserve), or participant’s aerobic fitness level above the 75th percentile for their age and sex by a time walking test)	Cardio group: a 10-month of tri-weekly training sessions (10-minute warm-up, 25–30 minutes of aerobic exercise on the equipment of the participant’s choice (treadmill, stair-stepping machine, stationary cycle, and elliptical machine), and a 10-minute cool down. Flex-Tone group: A 10-month tri-weekly training sessions (10-minute warm-up, 25–30 minutes of strength, flexibility, and balance exercises (yoga, Tai Chi, Flex bands, free hand weights, resistance weight training machines, and stability balls), and a 10-minute cool down; 8–10 exercises of 1–15 repetitions each were performed	Reaction time tests including simple reaction time, 8-choice reaction time, 8-choice incompatible reaction time, and Go/No-Go reaction time Stroop Color and Word Test Wisconsin Card Sort Test
Taaffe et al^Citation58 Prospective study	Physical activity was assessed at baseline by self-reporting and performance. The incident dementia was assessed at baseline and follow-up using CASI. Follow-up: at 3 and 6 years	2,263 subjects All males 71–92 years Inclusion criteria: enrollment in the Honolulu-Asia Aging Study; Japanese-American men born between 1900 and 1919 living on the island of Oahu, Hawaii. Exclusion criteria: dementia	None Physical activity assessment: a self-reported questioner. Physical function assessment: four performance tasks, ie, timed walk, sitting-to-standing time, grip strength, and balance. Cognitive status assessment: CASI used as the initial assessment. For CASI <74, subjects underwent a second phase of screening (a repeat CASI and administration of the IQCODE). Men with an IQCODE score of >3.6 underwent a third phase assessment (a standardized interview and neuropsychological battery, neurological examination, neuroimaging, and blood testing)	CASI (scores <74 indicative of possible dementia) IQCODE (scores <3.6 indicative of probable dementia) Diagnoses were finally decided by consensus of an appointed expert panel
Van Gelder et al^Citation59 Prospective study	Physical activity was assessed at baseline and at follow-up by using a self-administered questionnaire, and cognitive status was assessed at baseline and at follow-up by using MMSE. Follow-up: at 5 and 10 years	295 subjects All males 70–90 years Inclusion criteria: participants of the Surviving cohorts of the Seven Countries Study in Europe. Exclusion criteria: poor health (myocardial infarction, stroke, diabetes, or cancer); severe cognitive impairment (MMSE <18)	None Physical fitness assessment: a self-administered questionnaire. Physical activity was categorized into four groups: <30, 31–60, 61–120, and >120 minutes per day. Cognitive status assessment: MMSE	MMSE (scores <18 indicative of cognitive decline)
Wang et al^Citation60 Prospective study	Physical fitness was assessed at baseline by using a physical function test battery and cognitive function was assessed at baseline and follow-up by using a neurocognitive test battery. Follow-up: biennially through October 2003 (8–10 years)	2,228 subjects 863 males versus 1,365 females ≥65 years Inclusion criteria: participants of the Adult Changes in Thought study (1994–1996) exclusion criteria: CASI <86; dementia; invalid measurements on the cognitive performance test or physical performance test at baseline; persons without a follow-up examination	None Physical fitness assessment: Four different physical performance tests (timed walk, seating-to-standing time, standing balance, grip strength). Cognitive function assessment: CASI	CASI (score ≥86 were categorized as dementia-free)
Wang et al^Citation15 Prospective study	Leisure activity levels and cognitive status assessment were performed at baseline and follow-up. Follow-up: mean 2.4 (2.3–2.6) years	1,463 subjects 744 males and 719 females ≥65 years Participants of a longitudinal population-based study of aging in the People’s Republic of China between 2003 and 2005. Inclusion criteria: residents aged ≥65 years in the study regions. Exclusion criteria: baseline global cognitive score in the bottom 10%; physical disability	None Leisure activities assessment: a self-reported questionnaire in predefined list of mental, physical and social activities. Cognitive assessment: face-to-face interviews at the home of subjects using the followings; CSID, Word List Learning, Word List Recall, IU Story Recall, Animal Fluency Test, IU Token Test	Global cognitive function: CSID Episodic memory: Word List Learning, Word List Recall, IU Story Recall Language: Animal Fluency Test Executive function: IU Token Test
Williamson et al^Citation8 RCT	Subjects were randomized to a control group (n=52) or a physical activity treatment group (n=50). Physical fitness was assessed at baseline and follow-up using a battery of performance tests for balance, walking speed, and sitting-to-standing time. Cognitive function was assessed at baseline and follow-up by using a neuropsychological test battery. Follow-up: 12 months	102 participants 50 males and 72 females 70–89 years Participants of the LIFE-P study Inclusion criteria: sedentary lifestyle; ability to walk 400 m in 15 minutes without resting or assistance; SPPB score ≤9. Exclusion criteria: MMSE <21; life expectancy of <12 months; heart disease; severe neurological conditions such as Parkinson’s disease during time of study	Treatment group: physical activity intervention consisting of a combination of aerobic, strength, balance, and flexibility exercises divided into 3 phases: adoption (weeks 1–8), transition (weeks 9–24), and maintenance (week 25 to end of study). Control group: health education intervention designed to provide attention and health education to participants. Participants met in small groups weekly for the first 26 weeks and then monthly to the end of the study	Digit Symbol Substitution Test Modified Stroop Test MMSE The Rey Auditory Verbal Learning Test
Yaffe et al^Citation16 Prospective study	Physical activity was self-reported at baseline through both interview and questionnaire. Cognitive function was assessed at baseline and follow-up using the 3MS. Follow-up: 6–8 years	5,925 subjects All females ≥65 years Inclusion criteria: participants of the Study of Osteoporotic Fractures (a prospective study for risk factors of fractures in Baltimore, MD, Minneapolis, MN, Pittsburgh, PA, or Portland, OR, USA). Exclusion criteria: black women; unable to walk without assistance; bilateral hip replacements; baseline cognitive impairment; baseline physical limitations	None Physical fitness assessment: a self-reported questionnaire and a modified Paffenbarger scale (to quantify frequency and duration of weekly participation in 33 different physical activities) administered by trained interviewees. Cognitive function assessment: 3MS	3MS score (cognitive decline defined as a decrease in 3 or more points from baseline to follow-up)

Abbreviations: 3MS, Modified Mini-Mental State; ACT, Adult Changes in Thought; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive subscale; BMI, body mass index; BP, blood pressure; CASI, Cognitive Abilities Screening Instrument; CSID, Community Screening for Dementia; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; Health ABC, Health, Aging, and Body Composition; GDS, Geriatric Depression Scale; YPAS, Yale Physical Activity Survey; LIFE-P, Lifestyle Interventions and Independence for Elders Pilot; MDB, Mental Deterioration Battery; MMSE, Mini-Mental State Examination; RBMT, Rivermead Behavioural Memory Test; FCSRT, Free and Cued Selective Reminding Test; MRI, magnetic resonance imaging; TMT, Trail Making Tests; SPMSQ, Short Portable Mental Status Questionnaires; 3GM, Modified Mini-Mental Status Examination; MoVIES, Monongahela Valley Independent Elders Survey; SPPB, Short Physical Performance Battery; RCT, randomized controlled trial; WHICAP, Washington Heights-Inwood Columbia Aging Project; IQCODE, Informant Questionnaire on Cognitive Decline in the Elderly; AD, Alzheimer’s disease; RM, repetition maximum; IU, Indiana University.

Table 3 Results of included studies

Source and study design	Results
Buchman et al^Citation22 Prospective study	Total daily physical activities were associated with incident Alzheimer’s disease (hazard ratio 0.477, 95% confidence interval 0.273–0.832).
Busse et al^Citation17 RCT	After 9 months, the physical activity group showed a significant increase in RBMT score from pre-test to post-test, while the control group showed no increase.
Bixby et al^Citation62 Observational	A small but significant association between physical fitness and executive function in the sample of older men and women.
Cassilhas et al^Citation18 RCT	Both moderate-intensity and high-intensity resistance exercise programs had equally beneficial effects on cognitive functioning. However, the study was not able to identify a dose-response relationship between level of exercise and level of cognitive functioning.
Geda et al^Citation61 Case control	The odds ratio for any frequency of exercise of at least a moderate level in late life was 0.68, suggesting that any frequency of moderate-intensity exercise performed in late life is associated with a reduced odds ratio of mild cognitive impairment.
Klusmann et al^Citation10 RCT	Both the exercise group (mean ± SD change 2.09±2.66, P<0.001) and the computer group (mean ± SD change 1.89±2.88, P<0.001) showed improved delayed story recall. They maintained performance in delayed word recall and working memory (time measure) as opposed to the control group that showed a decline (mean ± SD change −0.91±2.15, P=0.001, and mean ± SD change 0.24±0.68, P=0.04, respectively). In conclusion, in older healthy women, exercise and computer classes seem to generate equivalent beneficial effects.
Ku et al^Citation11 Prospective study	Using the multivariate adjustment (controlling for sociodemographic variables, lifestyle behavior, and health status), higher initial levels of physical activity were significantly associated with better initial cognitive performance (standardized coefficient β=0.17). A higher level of physical activity at baseline was significantly related to slower decline in cognitive performance, as compared with a lower level of activity (β=0.22). The authors conclude that physical activity in later life is associated with slower age-related cognitive decline.
Larson et al^Citation55 Prospective study	During the follow-up period, 158 participants developed dementia while 107 developed Alzheimer’s disease. The interaction between exercise and incident dementia or Alzheimer disease was found to be statistically significant. The incidence rate of dementia was 13.0 per 1,000 person-years for participants who exercised 3 or more times per week, compared with 19.7 per 1,000 person-years for those who exercised less than 3 times per week. Similar results were observed in analyses for incident Alzheimer’s disease.
Laurin et al^Citation12 Prospective study	The results showed that, compared with no exercise, physical activity was significantly associated with lower risks of cognitive impairment of all types, including dementia and Alzheimer’s disease. Furthermore, a significant dose-response relationship was observed whereby greater physical activity was associated with increased protection for cognitive decline and disease.
Lytle et al^Citation13 Prospective study	A significant negative association (positive effect of exercise) between both low and high exercise and cognitive decline was observed.
Middleton et al^Citation14 Prospective study	The results showed that older adults in the highest level of activity energy expenditure had lower odds of incident cognitive impairment than those in the lowest levels of activity energy expenditure. Furthermore, a significant dose-response relationship was observed between incident activity energy expenditure and incidence of cognitive impairment.
Miu et al^Citation9 RCT	Eighty-two patients were available for analysis. The results showed no statistically significant difference between the treatment or control groups in terms of cognitive function.
Mortimer et al^Citation19 RCT	One hundred and twenty subjects were analyzed. In comparison with a no intervention group, Tai Chi and social intervention showed an increase of brain volume via magnetic resonance imaging (P<0.05) and improvement in several neuropsychological measures (P<0.05). No difference was observed between the walking and the no intervention group. This result differs from the previous trials in that the increase of brain volume and cognitive function in the current study is associated with nonaerobic exercise and social interaction.
Muscari et al^Citation20 RCT	One hundred and nine patients were available for analysis. A significant decrease in MMSE score in the control group was observed, and the odds ratio for treated older adults having stable cognitive status one year later (as compared with the control group) was 2.74, suggesting that a 12-month endurance exercise training program may delay the onset of age-related cognitive decline in the elderly.
Nagamatsu et al^Citation26 RCT	Resistance training participants had significantly improved performance on the Stroop Test, an executive cognitive test of selective attention/conflict resolution and the associated memory task compared with subjects in a balance and tone training group (P=0.04 and P=0.03, respectively). This study suggests that twice-weekly resistance training could alter the trajectory of cognitive decline in seniors with mild cognitive impairment.
Nguyen et al^Citation27 RCT	There were no significant differences between balance, sleep quality, and cognitive performance test. At the end of the study, participants in the Tai Chi training group showed a significantly (P<0.001) higher Trail Making Test score in part A (44.2±4.5 versus 35±4.3) and part B (118.3±6.4 versus 102±5).
Podewils et al^Citation56 Prospective study	Participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 compared with those in the lowest quartile, and participants who participated in more than four physical activities had a relative risk of dementia of 0.51 as compared with those who participated in 0 or 1 physical activities. Similar results were observed with risk of Alzheimer’s disease.
Ravaglia et al^Citation23 Prospective study	Physical activity is associated with a lowered risk of vascular dementia, but not of Alzheimer’s disease.
Scarmeas et al^Citation57 Prospective study	During a mean of 5.4 years of follow-up, a total of 282 incident Alzheimer’s disease cases occurred. The hazard ratio for some physical activity (compared with no physical activity) was 0.67, and for much physical activity was 0.67. This study suggests that physical activity is associated with a reduced risk for Alzheimer’s disease.
Schuit et al^Citation24 Prospective study	Subjects with one hour or less of daily physical activity were at doubly increased risk of cognitive decline as compared with subjects who participated in more than one hour of physical activity daily. This study suggests that promotion of physical activity at an advance aged may reduce the risk of cognitive decline.
Smiley-Oyen et al^Citation21 RCT	The results showed improvements in performance on the Stroop Color and Word Test only in the aerobic exercise group, and the study failed to show a dose-response relationship.
Taaffe et al^Citation58 Prospective study	For men with low physical function at baseline, high levels of exercise were associated with half the dementia risk as compared with men who were the least active. A moderate level of physical activity was found to be protective, because the risk of dementia and Alzheimer’s disease decreased significantly with higher levels of physical activity. However, the study was not able to identify a correlation between dementia and Alzheimer’s disease risk and physical activity in men with moderate or high levels of physical activity at baseline.
Van Gelder et al^Citation59 Prospective study	While there was no difference in the rates of cognitive decline between men with a high or low duration of physical activity at baseline, it was observed that a decrease in physical activity duration >60 minutes per day over 10 years resulted in a decline of 1.7 points in the MMSE. Further, men in the lowest physical activity intensity quartile had a 10-year cognitive decline 1.8 times greater than that observed in men in the higher physical activity intensity quartiles. This study suggests that participation in physical activities of at least low-medium intensity in old age may delay the onset of cognitive decline.
Wang et al^Citation60 Prospective study	During the 10-year period, 319 participants developed dementia and 221 developed Alzheimer’s disease. The results showed that a one-point decrease in performance-based physical function test scores was associated with an increased risk of dementia and Alzheimer’s disease. This study suggests that poor physical function may lead to onset of dementia and Alzheimer’s disease, while higher levels of physical fitness may delay onset of cognitive decline and disease.
Wang et al^Citation15 Prospective study	A high level of physical activity was related to less decline in episodic memory (P<0.05) and language (P<0.01). When mental, physical, and social activities were integrated into a composite activity index, a dose-response pattern was observed.
Williamson et al^Citation8 RCT	Ninety participants were available for analysis at the end of the study. The results did not show a significant difference between the groups; however, improvements in cognitive test scores on the Digit Symbol Substitution Test, Rey Auditory and Verbal Learning Test, and modified Stroop Test were associated with improvements in physical function.
Yaffe et al^Citation16 Prospective study	Women with a greater baseline physical fitness level were less likely to undergo cognitive decline during the 6–8-year follow-up period. A dose-response relationship was observed whereby cognitive decline occurred in 17%, 18%, 22%, and 24% of women in the highest, third, second, and lowest quartiles of physical activity as measured by blocks walked per week. Similar results were obtained when analyzing quartiles of kilocalorie expenditure. This study suggests that women with higher levels of baseline physical activity and fitness are less likely to develop cognitive decline.

Abbreviations: RBMT, Rivermead Behavioural Memory Test; RCT, randomized controlled trial; MMSE, Mini-Mental State Examination.

Figure 1 Description of studies which were identified, screened, and included in the systematic review.

Table 4 Association between physical activity and cognitive function in selected studies

Level of association	Number of studies	References
Significant	26	^Citation8,Citation10^–^Citation24,Citation26,Citation27,Citation55^–^Citation62
Insignificant	1	^Citation9
No association	0	N/A
Total	27	(See above references)

Abbreviation: N/A, not applicable.

Table S1 Agency for Healthcare Research and Quality Methods summary ratings of quality of individual studies

Good (low risk of bias)	These studies have the least bias and results are considered valid. A study that adheres mostly to the commonly held concepts of high quality including the following: a formal randomized controlled design; clear description of the population, setting, interventions, and comparison groups; appropriate measurement of outcomes; appropriate statistical and analytic methods and reporting; no reporting errors; low dropout rate and clear reporting of dropouts.
Fair	These studies are susceptible to some bias, but it is not sufficient to invalidate the results. They do not meet all the criteria required for a rating of good quality because they have some deficiencies, but no flaw is likely to cause major bias. The study may be missing information, making it difficult to assess limitations and potential problems.
Poor (high risk of bias)	These studies have significant flaws that imply biases of various types that may invalidate the results. They have serious errors in design, analysis, or reporting; large amounts of missing information; or discrepancies in reporting.

Source: Agency for Healthcare Research and Quality Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews (http://www.ahrq.gov/).

Table S2 Characteristics of excluded studies

Andel et al^Citation1	The study examines the effect of mid-life, not late-life, physical activity on cognition.
Baker et al^Citation2	Participants were too young to meet the given inclusion criteria of this review.
Barnes et al^Citation3	Participants were too young to meet the given inclusion criteria of this review.
Brown et al^Citation4	The study contained too few participants and participants were too young to meet the given inclusion criteria of this review.
Chang et al^Citation5	Examines the effect of mid-life, not late-life, physical activity on cognition.
Colcombe et al^Citation6	The study contained too few participants and participants were too young to meet the given inclusion criteria of this review.
Devore et al^Citation7	Participants were too young to meet the given inclusion criteria of this review.
Etgen et al^Citation8	Participants were too young to meet the given inclusion criteria of this review.
Fabre et al^Citation9	The duration of the study was too short to meet the given inclusion criteria of this review.
Floel et al^Citation10	Participants were too young to meet the given inclusion criteria of this review.
Gillum et al^Citation11	The outcome measure was death; this does not meet the given inclusion criteria for this review.
Hassett et al^Citation12	Participants were patients who had suffered traumatic brain injury; this was an exclusion criterion for the review.
Kasai et al^Citation13	The study contained too few participants to meet the given inclusion criteria of this review.
Lautenschlager et al^Citation14	Participants were too young to meet the given inclusion criteria of this review.
Liu-Ambrose et al^Citation15	Participants were elderly patients who had specifically suffered falls; this was an exclusion criterion for the review.
McAuley et al^Citation16	The study contained too few participants and participants were too young to meet the given inclusion criteria of this review.
McAuley et al^Citation17	Outcome measures included social-relation capacity and well-being; this does not meet the given inclusion criteria for this review.
Netz et al^Citation18	Participants were too young to meet the given inclusion criteria of this review.
O’Dwyer et al^Citation19	The duration of the trial was too short to meet the given inclusion criteria of this review.
Ojofeitimi et al^Citation20	Participants were too young to meet the given inclusion criteria for this review.
Parekh et al^Citation21	Participants were patients with lung disease; this was an exclusion criterion for this review.
Rovio et al^Citation22	The study examines the effect of mid-life, not late-life, physical activity.
Rovio et al^Citation23	The study examines the effect of mid-life, not late-life, physical activity.
Scherder et al^Citation24	The duration of the trial was too short to meet the given inclusion criteria for this review.
Shubert et al^Citation25	The duration of the trial was too short to meet the given inclusion criteria for this review.
Vercambre et al^Citation26	Participants were patients specifically with vascular disease; this was an exclusion criterion for the review.
Verghese et al^Citation27	The study examines the effect of cognitive, not physical, leisure activities on late-life cognition.
Voelcker-Rehage et al^Citation28	The study contained too few participants to meet the given inclusion criteria for this review.
Weuve et al^Citation29	Participants were too young to meet the given inclusion criteria for this review.
Wolinsky et al^Citation30	The study examines the effect of cognitive, not physical, activities on late-life cognition.

Table S3 Grouping of cognitive tests and studies of cognitive function

Cognitive domain	Name of test	References
Cognitive speed	Simple reaction time 8-Choice reaction time Go/no-go reaction time Digit symbol substitution test Trail making test	Smiley-Oyen et al^Citation31 Smiley-Oyen et al^Citation31 Smiley-Oyen et al^Citation31 Williamson et al^Citation32 Klusmann et al,^Citation33 Nguyen et al,^Citation34 Nagamatsu et al^Citation35
Immediate verbal memory function	Wechsler Adult Intelligence Scale The Rey Auditory Verbal Learning Test	Busse et al^Citation36 Williamson et al^Citation32
Global cognitive function	Mini-Mental State Examination Modified Mini-Mental State Examination	Lytle et al,^Citation37 Miu et al,^Citation38 Muscari et al,^Citation39 Ravaglia et al,^Citation40 Schuit et al,^Citation41 Van Gelder et al,^Citation42 Williamson et al,^Citation32 Laurin et al,^Citation43 Klusmann et al^Citation33 Middleton et al,^Citation44 Podewils et al,^Citation45 Yaffe et al^Citation46
Cognitive inhibition	Stroop Color and Word Test	Bixby et al,^Citation47 Smiley-Oyen et al,^Citation31 Williamson et al,^Citation32 Nagamatsu et al^Citation35
Working memory	Direct and Indirect Digit Span Rivermead Behavioral Memory Test Memory Complaints Scale	Busse et al^Citation36 Busse et al^Citation36 Cassilhas et al,^Citation48 Busse et al^Citation36
Differentiation between dementia and Alzheimer’s disease	Cambridge Cognitive Test	Busse et al^Citation36
Verbal/nonverbal intelligence Sustained attention Presence of dementia	Kaufman Brief Intelligence Test Toulouse-Pieron Concentration Attention Test Cognitive Abilities Screening Instrument Informant Questionnaire on Cognitive Decline in the Elderly Community Screening for Dementia	Bixby et al^Citation47 Cassilhas et al^Citation48 Taaffe et al,^Citation49 Wang et al^Citation51 Taaffe et al^Citation49 Wang et al^Citation50
Presence of Alzheimer’s disease	Alzheimer’s Disease Assessment Scale-Cognitive Subscale Mental Deterioration Battery	Miu et al^Citation38 Ravaglia et al^Citation40
Executive function	Wisconsin Card Sort Test Rey-Osterrieth Complex Figure Test	Smiley-Oyen et al^Citation31 Williamson et al,^Citation32 Wang et al^Citation51

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