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Supplemental InformationExercise and hippocampal memory systemsMichelle W. Voss1, Carmen Soto2, Seungwoo Yoo3, Matthew Sodoma1, Carmen Vivar2, Henriette van Praag31 Department of Psychological and Brain Sciences, University of Iowa2 Laboratory of Neurogenesis and Neuroplasticity. Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City.3 Department of Biomedical Science, Charles E. Schmidt College of Medicine, and Brain Institute, Florida Atlantic University, Jupiter, FL 33458, USAI. Methodologies used to measure aerobic exercise intensity and cardiorespiratory fitness Aerobic exercise can be defined as exercise to improve cardiorespiratory fitness that is fueled primarily on aerobic metabolism, which converts inspired oxygen to physical work. Aerobic physical activity (PA) intensity can be measured subjectively [“how hard are you working?” with answers on the Ratings of Perceived Exertion (RPE) scale on 6-20] or objectively based on heart rate in comparison to a personalized maximum heart rate (HRmax) ADDIN EN.CITE <EndNote><Cite><Author>Norton</Author><Year>2010</Year><RecNum>4783</RecNum><DisplayText>[2]</DisplayText><record><rec-number>4783</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1538604403">4783</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Norton, K.</author><author>Norton, L.</author><author>Sadgrove, D.</author></authors></contributors><auth-address>University of South Australia, Adelaide, South Australia, Australia. k.norton@unisa.edu.au</auth-address><titles><title>Position statement on physical activity and exercise intensity terminology</title><secondary-title>J Sci Med Sport</secondary-title></titles><periodical><full-title>J Sci Med Sport</full-title></periodical><pages>496-502</pages><volume>13</volume><number>5</number><edition>2009/12/17</edition><keywords><keyword>Energy Metabolism/physiology</keyword><keyword>Exercise/*physiology</keyword><keyword>Humans</keyword><keyword>Metabolic Equivalent/physiology</keyword><keyword>Motor Activity/*physiology</keyword><keyword>Practice Guidelines as Topic</keyword><keyword>Sports Medicine/*standards</keyword><keyword>*Terminology as Topic</keyword></keywords><dates><year>2010</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1878-1861 (Electronic)
1878-1861 (Linking)</isbn><accession-num>20005170</accession-num><urls><related-urls><url>;[2]. A given intensity can be specified as a proportion of one’s maximum heart rate (HRmax) (e.g., intensity = 0.60 could indicate 60% of HRmax in the following equation, Target Heart Rate = intensity* HRmax). HRmax can be estimated based on age (e.g., a common equation used to estimate age-predicted HRmax is 220 - age), but this formula will not work well for everyone ADDIN EN.CITE <EndNote><Cite><Author>Sarzynski</Author><Year>2013</Year><RecNum>5060</RecNum><DisplayText>[3]</DisplayText><record><rec-number>5060</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1547148747">5060</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sarzynski, M. A.</author><author>Rankinen, T.</author><author>Earnest, C. P.</author><author>Leon, A. S.</author><author>Rao, D. C.</author><author>Skinner, J. S.</author><author>Bouchard, C.</author></authors></contributors><auth-address>Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, 70808.</auth-address><titles><title>Measured maximal heart rates compared to commonly used age-based prediction equations in the Heritage Family Study</title><secondary-title>Am J Hum Biol</secondary-title></titles><periodical><full-title>Am J Hum Biol</full-title></periodical><pages>695-701</pages><volume>25</volume><number>5</number><edition>2013/08/06</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>African Continental Ancestry Group</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Canada</keyword><keyword>European Continental Ancestry Group</keyword><keyword>Exercise Test/*methods</keyword><keyword>Female</keyword><keyword>*Heart Rate</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Motor Activity</keyword><keyword>Sex Factors</keyword><keyword>United States</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>Sep-Oct</date></pub-dates></dates><isbn>1520-6300 (Electronic)
1042-0533 (Linking)</isbn><accession-num>23913510</accession-num><urls><related-urls><url>;[3]. Rather, ideally HRmax is determined during a maximal exercise test that pushes you to exhaustion. When this is not possible, a modified equation of HRmax = 208 - (0.7*age) is preferable for estimating maximum heart rate ADDIN EN.CITE <EndNote><Cite><Author>Tanaka</Author><Year>2001</Year><RecNum>5061</RecNum><DisplayText>[4]</DisplayText><record><rec-number>5061</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1547149349">5061</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tanaka, Hirofumi</author><author>Monahan, Kevin D.</author><author>Seals, Douglas R.</author></authors></contributors><titles><title>Age-predicted maximal heart rate revisited</title><secondary-title>Journal of the American College of Cardiology</secondary-title></titles><periodical><full-title>Journal of the American College of Cardiology</full-title></periodical><pages>153-156</pages><volume>37</volume><number>1</number><section>153</section><dates><year>2001</year></dates><isbn>07351097</isbn><urls></urls><electronic-resource-num>10.1016/s0735-1097(00)01054-8</electronic-resource-num></record></Cite></EndNote>[4]. Additionally, when participants are on medications that could affect exercise effects on HR, such as beta blockers, or if they have a heart condition affecting HR monitor readings (e.g., arrhythmia), then subjective measures are particularly informative. By comparison, Heart Rate Reserve (HRR) also takes into account resting heart rate (HRresting) [%HRR= intensity*(HRmax – HRresting) + HRresting). For instance, this table shows a typical description of different aerobic exercise intensities:Table S1. Aerobic intensity levels Intensity categoryObjective measuresSubjective measures(e.g., Borg’s RPE 6-20)Qualitative description*Sedentary/Resting< 40% HRmax< 20% HRRRPE < 8- Sitting or lying downLight40 < 55% HRmax20 < 40% HRRRPE 8-10- No noticeable change in breathing rate or sweating- Can be sustained for an hour or moreModerate55 < 70% HRmax40 < 60% HRRRPE 11-13- Slight changes in breathing, but can be done comfortably while holding a conversation- Can be sustained for 30 minutes to an hourVigorous70 < 90% HRmax60 < 85% HRRRPE 14-16- Heavier breathing than moderate, cannot sustain conversation without interruption- Can be sustained for up to 30 minutesHigh> 90% HRmax> 85% HRRRPE > 17- Can be sustained for up to 10 minutes- Heavy breathing, cannot sustain conversation without interruptionTable S1. Modified version of Table 1 in ADDIN EN.CITE <EndNote><Cite><Author>Norton</Author><Year>2010</Year><RecNum>4783</RecNum><DisplayText>[2]</DisplayText><record><rec-number>4783</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1538604403">4783</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Norton, K.</author><author>Norton, L.</author><author>Sadgrove, D.</author></authors></contributors><auth-address>University of South Australia, Adelaide, South Australia, Australia. k.norton@unisa.edu.au</auth-address><titles><title>Position statement on physical activity and exercise intensity terminology</title><secondary-title>J Sci Med Sport</secondary-title></titles><periodical><full-title>J Sci Med Sport</full-title></periodical><pages>496-502</pages><volume>13</volume><number>5</number><edition>2009/12/17</edition><keywords><keyword>Energy Metabolism/physiology</keyword><keyword>Exercise/*physiology</keyword><keyword>Humans</keyword><keyword>Metabolic Equivalent/physiology</keyword><keyword>Motor Activity/*physiology</keyword><keyword>Practice Guidelines as Topic</keyword><keyword>Sports Medicine/*standards</keyword><keyword>*Terminology as Topic</keyword></keywords><dates><year>2010</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1878-1861 (Electronic)
1878-1861 (Linking)</isbn><accession-num>20005170</accession-num><urls><related-urls><url>;[2]: Norton, K., Norton, L., Sadgrove, D., 2010. Position statement on physical activity and exercise intensity terminology. J Sci Med Sport 13(5), 496-502. HRmax, maximum heart rate; HRR, heart rate reserve; RPE, ratings of perceived exertion. Similar training zones have been published by the American College of Sports Medicine PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYXJiZXI8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [5]. *There is some variability among adults on how their objective measures relate to RPE, and training status will affect their ability to exercise at for a given intensity at the estimated duration. However, generally the ability to hold a conversation (i.e., the “talk test”) is a useful qualitative indicator of the transition between moderate and vigorous intensity.II. Aerobic training paradigms utilized to evaluate cognition and brain in older adults Exercise training protocols from representative studies cited in our main text are here examined in more detail. Note that because participants were inactive when they started the intervention, (1) their pre-training cardiorespiratory fitness is quite low (typically in bottom 10th% of their age and sex matched peers), and (2) there is a “ramping” period where duration and/or intensity is gradually increased to a target training zone. Below, we summarize training intensity based on the peak intensity zone targeted during each intervention PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJuZXM8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [1, 6-11]. The training intensities listed for each study refer to zones of minimum and maximum target heart rates for a given target intensity during training sessions. Ideally, as described above, each participant will have completed a supervised exercise test to determine their personalized maximum heart rate. With this value, personalized target heart rate zones can be determined, and even adjusted during training if exercise tests can be repeated. Accordingly, it is best practice for participants to wear HR monitors during the intervention so that HR data can be monitored and used for feedback during training, and the validity of the intervention manipulation can be verified. Figure S1. Average change in fitness from representative studiesFigure S1. Range of changes in cardiorespiratory fitness (mL/kg/min) across representative training studies. Pre- and post-training fitness are measured with supervised maximal graded exercise tests. The x-axis indicates how much on average the aerobic walking group improved fitness following the intervention, and y-axis indicates different studies ordered from least to most change in fitness. The color coding indicates the average pre-training fitness level, which is a relevant factor in considering %change and shows participants in reviewed studies start with relatively low fitness (see discussion below). HRmax, maximum heart rate; HRR, heart rate reserve; mo, months; wk, week; min, minutes.Specifically, Erickson et al., 2011 ADDIN EN.CITE <EndNote><Cite><Author>Erickson</Author><Year>2011</Year><RecNum>4515</RecNum><DisplayText>[1]</DisplayText><record><rec-number>4515</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1533164216">4515</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Erickson, KI</author><author>Voss, MW</author><author>Prakash, RS</author><author>Basak, C</author><author>Szabo, A</author><author>Chaddock, L</author><author>Kim, JS</author><author>Heo, S</author><author>Alves, H</author><author>White, SM</author><author>Wojcicki, TR</author><author>Mailey, E</author><author>Vieira, VJ</author><author>Martin, SA</author><author>Pence, BD</author><author>Woods, JA</author><author>McAuley, E</author><author>Kramer, AF</author></authors></contributors><auth-address>Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</auth-address><titles><title>Exercise training increases size of hippocampus and improves memory.</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>3017-22</pages><volume>108</volume><number>7</number><keywords><keyword>cardiovascular fitness hypothesis, exercise, aging, hippocampus</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb 15</date></pub-dates></dates><publisher>United States</publisher><accession-num>21282661</accession-num><urls><related-urls><url>;[1] measured fitness at 6 months and 12 months over a 12 month intervention, showing that longer training will lead to greater fitness gains. In addition, Vidoni et al., 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5WaWRvbmk8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [7] examined the effect of increasing the duration of training per week, and also found a dose-response effect with the longest training time of 225 min/week resulting in the largest fitness gains. It is also worth highlighting that average cardiorespiratory fitness declines about 2% per year ADDIN EN.CITE <EndNote><Cite><Author>Fleg</Author><Year>2005</Year><RecNum>5038</RecNum><DisplayText>[12]</DisplayText><record><rec-number>5038</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1546352701">5038</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fleg, J. L.</author><author>Morrell, C. H.</author><author>Bos, A. G.</author><author>Brant, L. J.</author><author>Talbot, L. A.</author><author>Wright, J. G.</author><author>Lakatta, E. G.</author></authors></contributors><auth-address>Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. flegj@nhlbi.</auth-address><titles><title>Accelerated longitudinal decline of aerobic capacity in healthy older adults</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><pages>674-82</pages><volume>112</volume><number>5</number><edition>2005/07/27</edition><keywords><keyword>Adult</keyword><keyword>Aerobiosis</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Aging/*physiology</keyword><keyword>Exercise/*physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Leisure Activities</keyword><keyword>Longitudinal Studies</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Oxygen Consumption</keyword><keyword>Physical Fitness</keyword><keyword>Reference Values</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 2</date></pub-dates></dates><isbn>1524-4539 (Electronic)
0009-7322 (Linking)</isbn><accession-num>16043637</accession-num><urls><related-urls><url>;[12] from the sixth decade onwards, and an average fitness level for a 60-year-old male is 36 mL/kg/min and for a female it is 30 mL/kg/min (for an online calculator, see ). By comparison, the typical pre-training average fitness in intervention studies described above with older adults is around 20 mL/kg/min, which is below the 10th percentile for 60 to 75 year-old males and females. Results from most training studies with cognitive and brain outcomes thus generally include primarily individuals that are well below average in their age and sex-predicted fitness, and yet still qualify to participate in the intervention (i.e., have not experienced major health problems or psychiatric disease). This is important to keep in mind when applying the results to the general population. Further, much less is known about the additional benefits of improved fitness for older adults with an already active lifestyle and high fitness levels.III. Individual differences in training response 51185381247052Figure S2.Figure S2. Variability within a given study ADDIN EN.CITE <EndNote><Cite><Author>Erickson</Author><Year>2011</Year><RecNum>4515</RecNum><DisplayText>[1]</DisplayText><record><rec-number>4515</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1533164216">4515</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Erickson, KI</author><author>Voss, MW</author><author>Prakash, RS</author><author>Basak, C</author><author>Szabo, A</author><author>Chaddock, L</author><author>Kim, JS</author><author>Heo, S</author><author>Alves, H</author><author>White, SM</author><author>Wojcicki, TR</author><author>Mailey, E</author><author>Vieira, VJ</author><author>Martin, SA</author><author>Pence, BD</author><author>Woods, JA</author><author>McAuley, E</author><author>Kramer, AF</author></authors></contributors><auth-address>Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</auth-address><titles><title>Exercise training increases size of hippocampus and improves memory.</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>3017-22</pages><volume>108</volume><number>7</number><keywords><keyword>cardiovascular fitness hypothesis, exercise, aging, hippocampus</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb 15</date></pub-dates></dates><publisher>United States</publisher><accession-num>21282661</accession-num><urls><related-urls><url>;[1] for the participants in the aerobic (walking) group. Attendance represents percentage of exercise sessions completed over the year-long intervention (3 sessions/week).Figure S2.Figure S2. Variability within a given study ADDIN EN.CITE <EndNote><Cite><Author>Erickson</Author><Year>2011</Year><RecNum>4515</RecNum><DisplayText>[1]</DisplayText><record><rec-number>4515</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1533164216">4515</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Erickson, KI</author><author>Voss, MW</author><author>Prakash, RS</author><author>Basak, C</author><author>Szabo, A</author><author>Chaddock, L</author><author>Kim, JS</author><author>Heo, S</author><author>Alves, H</author><author>White, SM</author><author>Wojcicki, TR</author><author>Mailey, E</author><author>Vieira, VJ</author><author>Martin, SA</author><author>Pence, BD</author><author>Woods, JA</author><author>McAuley, E</author><author>Kramer, AF</author></authors></contributors><auth-address>Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</auth-address><titles><title>Exercise training increases size of hippocampus and improves memory.</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>3017-22</pages><volume>108</volume><number>7</number><keywords><keyword>cardiovascular fitness hypothesis, exercise, aging, hippocampus</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb 15</date></pub-dates></dates><publisher>United States</publisher><accession-num>21282661</accession-num><urls><related-urls><url>;[1] for the participants in the aerobic (walking) group. Attendance represents percentage of exercise sessions completed over the year-long intervention (3 sessions/week).In addition to the variability in fitness gains across studies, there are large individual differences in training responses within studies. For example, the plot below summarizes individual participant changes in fitness (mL/kg/min) for those in the walking group in the Erickson et al., 2011 study ADDIN EN.CITE <EndNote><Cite><Author>Erickson</Author><Year>2011</Year><RecNum>4515</RecNum><DisplayText>[1]</DisplayText><record><rec-number>4515</rec-number><foreign-keys><key app="EN" db-id="zesdra95getsdoe5rtrxewwa920dtesz5pxz" timestamp="1533164216">4515</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Erickson, KI</author><author>Voss, MW</author><author>Prakash, RS</author><author>Basak, C</author><author>Szabo, A</author><author>Chaddock, L</author><author>Kim, JS</author><author>Heo, S</author><author>Alves, H</author><author>White, SM</author><author>Wojcicki, TR</author><author>Mailey, E</author><author>Vieira, VJ</author><author>Martin, SA</author><author>Pence, BD</author><author>Woods, JA</author><author>McAuley, E</author><author>Kramer, AF</author></authors></contributors><auth-address>Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.</auth-address><titles><title>Exercise training increases size of hippocampus and improves memory.</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>3017-22</pages><volume>108</volume><number>7</number><keywords><keyword>cardiovascular fitness hypothesis, exercise, aging, hippocampus</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb 15</date></pub-dates></dates><publisher>United States</publisher><accession-num>21282661</accession-num><urls><related-urls><url>;[1], which showed relatively smaller group changes (see Figure S1). Further, greater changes in fitness were related to greater increases in hippocampal volume for the walking but not the stretching group, suggesting that greater changes in fitness indicate greater benefit for hippocampal structure. Variation in fitness change can be partly explained by attendance to exercise sessions (shown here), and other factors, such as genetics, age, and measurement error. However, studies often see a correlation between change in fitness and hippocampal brain or memory outcomes even when controlling for a range of known factors. Thus, more research is needed to understand the mechanistic significance of change in fitness in relation to predicting improved hippocampal system memory outcomes. IV. Cognitive constructs examined in meta-analyses on training studies Recently, a number of meta-analyses have summarized the effects of aerobic exercise training on different aspects of cognition. 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ADDIN EN.CITE.DATA [13-23] with memory terms highlighted (yellow), including “visuospatial ability” which commonly includes configural memory tasks: Table S2. Summary of recent meta-analytic effect sizes of exercise training effects on cognitionMeta-analysisPopulationCognitive StatusCognitive Construct Grouping TermExercise effectExerciseSEControl effectControl SEStd Mean Diff (SMD)SMD SEBarha2017OlderNormalExecutive Function2.0640.249Barha2017OlderNormalEpisodic Memory0.0450.205Barha2017OlderNormalProcessing Speed0.4680.117Barha2017OlderNormalVerbal Fluency0.3510.078Barha2017OlderNormalVisuospatial Ability0.6450.259Colcombe2003OlderNormalControlled0.4610.0350.12Colcombe2003OlderNormalExecutive Function0.680.050.1Colcombe2003OlderNormalSpatial0.4260.060.08Colcombe2003OlderNormalCognitive Speed0.2740.050.08Forbes2015OlderMCICognition0.210.2Heyn2004OlderDementiaCognition0.570.07Kane2017OlderNormalExecutive-Attention-Processing SpeedInsufficientKane2017OlderNormalMemoryInsufficientLaw2014OlderMixedQualitativeQualitativeNorthey2018OlderNormalAttention0.270.07Northey2018OlderNormalExecutive Function0.340.07Northey2018OlderNormalMemory0.360.07Northey2018OlderNormalWorking Memory0.290.08Panza2018OlderDementia RiskCognition0.470.11Roig2013AdultsNormalLong Term Memory0.070.1Roig2013AdultsNormalShort Term Memory0.150.06Smith2010AdultsNormalAttention Proc-Speed0.1580.05Smith2010AdultsNormalDeclarative Memory0.1280.06Smith2010AdultsNormalExecutive Function0.120.05Smith2010AdultsNormalWorking Memory0.030.07Young2015OlderNormalAuditory Attention0.150.28Young2015OlderNormalCognitive Inhibition-0.060.12Young2015OlderNormalCognitive Speed0.120.11Young2015OlderNormalExecutive Function0.380.27Young2015OlderNormalMotor Function0.080.15Young2015OlderNormalPerception-0.010.25Young2015OlderNormalVerbal Memory Delayed0.10.13Young2015OlderNormalVerbal Memory Immediate0.080.24Young2015OlderNormalVisual Attention0.220.12Young2015OlderNormalVisual Memory Immediate-0.260.36Young2015OlderNormalWorking Memory0.10.13Table S2: Column for group “effect” denotes effect size as provided in the original meta-analysis. SMD, standardized mean difference between groups, which is an effect size estimating how much the effect favored a training group compared to a control group. SE, standard error of effect sizes. MCI, Mild cognitive impartment.V. Summary of results from meta-analyses at the task-level This section describes our method for summarizing results from aerobic training effects on different memory tasks (see Figure 1A in main text). We focused on standardized neuropsychological tasks that can predict accelerated age-related cognitive decline, cognitive impairment, and risk of progressing to dementia. These include delayed recall on word list learning (e.g., Rey Auditory Verbal Learning Task, Hopkins Verbal Learning Task, California Verbal Learning Task), delayed recall of details from stories (e.g., logical memory), and visuospatial configural memory (e.g., complex figure). Additionally, cognitive experimental tasks designed to tap into subtle decline of hippocampal function may be fruitful for early detection of physical activity effects on the deterioration process. Therefore, we also summarized results from tasks which have been proposed to specifically tap into processes that require the hippocampus (e.g., pattern separation, spatial navigation, relational memory). Although the meta-analyses included some populations with cognitive impairment, because we are interested in prevention and the preclinical phase, our summary of outcomes only includes cognitively normal middle age and older adults. Note also, a new quantitative meta-analysis would be beyond the scope of our review, so our aim was to simply count how often memory tasks showed statistically significant change from training (see Figure 1A in main text).Table S3. Hippocampal memory tasks evaluated for summary in Figure 1ATask labelTask versionsSearch termsVisuospatialRey-Osterrieth Complex Figure (ROCF), alternative versions of the complex figure task“ROCF”, “Rey-Osterrieth Complex Figure (ROCF)”, “rey-osterrieth”, “rey osterrieth complex figure”Word List LearningAuditory Verbal Learning task, California Verbal Learning task, Hopkins Verbal Learning task, List learning unspecified, Rey Auditory Verbal Learning taskRAVLT, “rey auditory”, “verbal learning”, CVLT, “california modified (CVLT)”, “california modified”, “california verbal”, “california learning”, HVLT, hopkins, “hopkins verbal”Story RecallLogical memory, Story Recall tasks unspecified“logical memory”RelationalVerbal or spatial paired associates tasks, face-name memory, face-place memory, any variant of memory for relations, spatial reconstruction.“Paired associate”, “relational memory”WayfindingNo standard task existsallocentric, “spatial navigation”, wayfinding,Mnemonic discriminationNo standard task exists“pattern separation”, “object discrimination”, “mnemonic discrimination”Table S3. Alternative versions of tasks that were included in the summary of training effects by memory tasks. A full database of studies, task outcomes, and a notebook showing the code used for creating the graph in Figure 1A are available here: Supplemental references:S ADDIN EN.REFLIST 1. Erickson, K. et al. (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 108 (7), 3017-22.S2. Norton, K. et al. (2010) Position statement on physical activity and exercise intensity terminology. J Sci Med Sport 13 (5), 496-502.S3. Sarzynski, M.A. et al. (2013) Measured maximal heart rates compared to commonly used age-based prediction equations in the Heritage Family Study. Am J Hum Biol 25 (5), 695-701.S4. Tanaka, H. et al. (2001) Age-predicted maximal heart rate revisited. Journal of the American College of Cardiology 37 (1), 153-156.S5. Garber, C.E. et al. (2011) American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 43 (7), 1334-59.S6. Barnes, D. et al. (2013) The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to enhance cognitive function in older adults. JAMA Intern Med 173 (9), 797-804.S7. Vidoni, E.D. et al. (2015) Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial. PLoS One 10 (7), e0131647.S8. Thomas, A.G. et al. (2016) Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise. NeuroImage 131, 162-170.S9. Voss, M.W. et al. (2018) Nutritional supplementation boosts aerobic exercise effects on functional brain systems. Journal of Applied Physiology.S10. Maass, A. et al. (2015) Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry 20 (5), 585-93.S11. Pereira, A. et al. (2007) An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 104 (13), 5638-43.S12. Fleg, J.L. et al. (2005) Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation 112 (5), 674-82.S13. Barha, C.K. et al. (2017) Sex differences in exercise efficacy to improve cognition: A systematic review and meta-analysis of randomized controlled trials in older humans. Front Neuroendocrinol 46, 71-85.S14. Colcombe, S. and Kramer, A. (2003) Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 14 (2), 125-30.S15. Forbes, D. et al. (2015) Exercise programs for people with dementia. Cochrane Database Syst Rev (4), CD006489.S16. Heyn, P. et al. (2004) The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis. Arch Phys Med Rehabil 85 (10), 1694-704.S17. Kane, R.L. et al. (2017) Interventions to Prevent Age-Related Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer’s-Type Dementia.S18. Law, L. et al. (2014) Effects of combined cognitive and exercise interventions on cognition in older adults with and without cognitive impairment: a systematic review. Ageing Res Rev 15, 61-75.S19. Northey, J.M. et al. (2018) Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med 52 (3), 154-160.S20. Panza, G.A. et al. (2018) Can Exercise Improve Cognitive Symptoms of Alzheimer's Disease? A Meta-Analysis. J Am Geriatr Soc.S21. Roig, M. et al. (2013) The effects of cardiovascular exercise on human memory: a review with meta-analysis. Neurosci Biobehav Rev 37 (8), 1645-66.S22. Smith, P. et al. (2010) Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med 72 (3), 239-52.S23. Young, J. et al. (2015) Aerobic exercise to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 4, CD005381. ................
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