Effect of 5 years of exercise intervention at different ...



Supplemental materialsEffect of 5 years of exercise intervention at different intensities on brain structure in older adults from the general population. A Generation 100 substudyPani Jasmine1,2, Reitlo Line Skarsem1,2, Evensmoen Hallvard R?e2, Lydersen Stian3, Wisl?ff Ulrik4,5, Stensvold Dorthe4,6, H?berg Asta Kristine1,2*1Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU (Norwegian University of Science and Technology), Trondheim, Norway; 2Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 3Department of Mental Health, Faculty of Medicine and Health Sciences, NTNU (Norwegian University of Science and Technology), Trondheim, Norway; 4Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU (Norwegian University of Science and Technology), Trondheim, Norway; 5School of Human Movement & Nutrition Sciences, University of Queensland, Queensland, Australia; 6Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, NorwayCorrespondence: Asta Kristine H?berg, MD, PhD1Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU (Norwegian University of Science and Technology), Trondheim, Norway NTNU, Faculty of Medicine and Health Sciences, N-7491 Trondheim, Norway 2Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway St. Olavs Hospital HF, Postbox 3250 Torgarden, NO-7006 Trondheim, NorwayTelephone: +47 90 25 91 47Email: asta.haberg@ntnu.noSupplementary ContentSupplementary MethodsSleep indexCRF and grip strengthSupplementary TablesSupplementary Table 1. Demographics and clinical data for the Generation 100 Study and Generation 100 brain MRI participants at baselineSupplementary Table 2. Demographics and clinical data for control, MICT and HIIT participants at the 1-year examinationSupplementary Table 3. Demographics and clinical data for control, MICT and HIIT participants at the 3-year examinationSupplementary Table 4. Demographics and clinical data for control, MICT and HIIT participants at the 5-year examinationSupplementary Table 5. Adherence to physical activity guideline for the control, and to the MICT and HIIT intervention for the MICT and HIIT groups given as number of participants (%) fulfilling the adherence requirementsSupplementary Table 6. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention (Model 1) in HIIT and MICT groups compared to control groupSupplementary Table 7. Linear mixed model analyses of brain volumes during 5 years of intervention, corrected for CRF (Model 2), in HIIT and MICT groups compared to control groupSupplementary Table 8. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention, corrected for CRF (Model 2), in HIIT and MICT groups compared to control groupSupplementary Table 9. Linear mixed model analyses of brain volumes during 5 years of intervention (Model 1) in combined MICT&HIIT group compared to control groupSupplementary Table 10. Linear mixed model analyses of brain volumes during 5 years of intervention, corrected for CRF (Model 2), in combined MICT&HIIT group compared to control group Supplementary Table 11. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention (Model 1) in combined MICT&HIIT group compared to control group Supplementary Table 12. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention, corrected for CRF (Model 2) in combined MICT&HIIT group compared to control group Supplementary Table 13. Linear mixed model analyses with CRF as dependent variable during 5 years of intervention in control, MICT and HIIT groupsSupplementary Table 14. Longitudinal linear mixed model analyses with CRF as dependent variable during 5 years of intervention in combined MICT&HIIT group compared to control groupReferencesSupplemental methodsSleep indexFrom the questionnaire an index for sleep was calculated based on the questions: “How often in the last three months have you: 1)?Had difficulty falling asleep at night? 2) Woken up repeatedly during the night? 3) Woken too early and couldn’t get back to sleep?”. The response options were: “Never/seldom” scored as 1, “Sometimes” scored as 2, “Several times a week” scored as 3 ADDIN EN.CITE <EndNote><Cite><Author>Bragantini</Author><Year>2019</Year><RecNum>1026</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>1026</rec-number><foreign-keys><key app="EN" db-id="v9rfwvrt19eswdepp2g5fsv8vpxzpt9x9dtt" timestamp="1584537145">1026</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bragantini, Daniela</author><author>Sivertsen, B?rge</author><author>Gehrman, Philip</author><author>Lydersen, Stian</author><author>Güzey, Ismail Cüneyt</author></authors></contributors><titles><title>Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study</title><secondary-title>BMC medical genetics</secondary-title></titles><periodical><full-title>BMC medical genetics</full-title></periodical><pages>1-7</pages><volume>20</volume><number>1</number><dates><year>2019</year></dates><isbn>1471-2350</isbn><urls></urls><electronic-resource-num> three questions were collapsed into one index. CRF and grip strengthCRF was assessed objectively as VO2peak using graded maximal exercise testing on a motor-driven treadmill (nInclusion = 102, n5-year = 78) or exercise bike (nInclusion = 3, n5-year = 7). Participants with cardiovascular diseases were tested under ECG monitoring and the exercise testing followed the guidelines of the American College of Cardiology/American Heart Association PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HaWJib25zPC9BdXRob3I+PFllYXI+MTk5NzwvWWVhcj48

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ADDIN EN.CITE.DATA 2. Participants warmed up at an individually adjusted submaximal level for 10 minutes. A mask for measuring oxygen consumption, blood pressure cuff, pulse belt and heart rate electrodes were then fitted on the participant. The test started with the speed and inclination from the last part of the warm-up period. The incline of the treadmill was increased by 2% or the speed was increased by 1 km/h about every second minute. Participants were encouraged to continue until exhaustion. VO2max was reached when the respiratory exchange ratio was ≥ 1.05 and VO2 did not increase more than 2 mL between two 30-seconds epochs. If the participant was unable to meet these criteria, VO2peak was estimated instead. VO2peak was calculated from the mean of the three successively highest 10-seconds VO2 registrations. During the study period, 26-34% of the participants did not achieve VO2max, and for those VO2peak was reported (Table 1, Supplementary Tables 2-4). The registered VO2max/peak values were normalized to body weight (mL/kg/min). See Stensvold et al ADDIN EN.CITE <EndNote><Cite><Author>Stensvold</Author><Year>2017</Year><RecNum>1383</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>1383</rec-number><foreign-keys><key app="EN" db-id="v9rfwvrt19eswdepp2g5fsv8vpxzpt9x9dtt" timestamp="1619517826">1383</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensvold, Dorthe</author><author>Sandbakk, Silvana Bucher</author><author>Viken, Hallgeir</author><author>Zisko, Nina</author><author>Reitlo, Line Skarsem</author><author>Nauman, Javaid</author><author>Gaustad, Svein Erik</author><author>Hassel, Erlend</author><author>Moufack, Marcel</author><author>Br?nstad, Eivind</author></authors></contributors><titles><title>Cardiorespiratory reference data in older adults: the generation 100 study</title><secondary-title>Medicine and science in sports and exercise</secondary-title></titles><periodical><full-title>Medicine and science in sports and exercise</full-title></periodical><pages>2206</pages><volume>49</volume><number>11</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>3 for more details on the VO2peak measurements.For grip strength the participants were tested three times on their dominant hand and the mean score of the three trials are reported.?Supplementary tablesSupplementary Table 1. Demographics and clinical data for the Generation 100 Study and Generation 100 brain MRI participants at baselineGeneration 100 Study(N=1462)Generation 100 brain MRI (N=105)p-valueWomena (%)50.549.50.85Living with othersa (%Yes)75.270.20.25Educationc %Primary school15.38.70.003 %High school35.226.9 %University49.564.4Smokinga (% No)91.591.30.94Ageb (years) 72.4 (2.1)72.0 (1.9)0.04Heightb (cm) 170.1 (8.8)170.1 (8.9)0.96Weightb (kg) 75.5 (13.5)75.2 (12.6)0.84Fatb (%) 30.3 (8.1)29.4 (7.7)0.27Muscle massb (%) 38.0 (4.9)38.6 (4.5)0.26BMIb (kg/m2) 26.0 (3.6)25.93 (3.3)0.85Visceral fatb (cm2)115.3 (33.3)112.5 (36.6)0.40Waist circumferenceb (cm) 94.2 (11.1)93.7 (10.6)0.64SBPb (mmHg)134.1 (17.6)133.9 (17.2)0.93DBPb (mmHg)75.2 (9.6)75.3 (8.5)0.88RHRb (beats/min) 65.1 (10.9)63.6 (9.4)0.19hsCRPc (mg/L) 2.4 (4.1)2.1 (3.4)0.38HbA1cc (%) 5.7 (0.5)5.6 (0.3)0.001Glucosec (mmol/L) 5.7 (0.9)5.6 (0.7)0.42HDLb (mmol/L) 1.7 (0.5)1.9 (0.6)0.01LDLb (mmol/L) 3.4 (1.0)3.4 (0.9)0.62TCb (mmol/L) 5.6 (1.1)5.8 (1.0)0.25TGb (mmol/L) 1.1 (0.6)1.0 (0.5)0.04Diabetesa (%No)94.698.10.13VO2peakb (mL/kg/min)28.6 (6.4)30.2 (6.4)0.01VO2peak or VO2max (%VO2max)a#59.865.40.27Grip strengthb (kg)34.4 (10.9)35.8 (10.4)0.21Sleep indexb (total score)5.4 (1.5)5.2 (1.5)0.13SF-8 Physical healtha51.9 (6.2)52.9 (5.9)0.07SF-8 Mental healtha54.1 (5.8)55.4 (4.4)0.02HADSb (total score)6.2 (4.4)4.6 (3.6)<0.001p-values < 0.05 are in bold font. The continuous measures are shown as mean and standard deviation in the parentheses. Categorical data is reported as percentages. a Chi-square; b t-test; c Mann-Whitney U test # Percentage of participants that achieved VO2max during the graded maximal exercise testing.BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; RHR: resting heart rate; hsCRP: high sensitivity C-reactive protein; HbA1c: glycated hemoglobin; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TC: total cholesterol; TG: triglycerides; SF-8: short form health survey questionnaire; HADS: Hospital Anxiety and Depression Scale.Supplementary Table 2. Demographics and clinical data for control, MICT and HIIT participants at the 1-year examinationControl(N=42)MICT(N=21)HIIT(N=31)Women (%) 52.452.445.2Living with others (%Yes) 65.071.474.2Education %Primary school4.814.36.7 %High school31.014.320.0 %University64.371.473.3Smoking (%No)90.295.290.3Age (years) 72.8 (1.8)72.9 (1.8)73.1 (2.0)Height (cm) 168.2 (9.2)170.8 (8.0)169.9 (8.7)Weight (kg) 72.0 (13.9)75.2 (10.2)74.4 (12.9)Fat (%) 29.4 (7.7)29.5 (7.9)27.3 (7.7)Muscle mass (%) 38.5 (4.6)38.7 (4.4)39.6 (4.2)BMI (kg/m2) 25.3 (3.8)25.8 (3.7)25.5 (3.1)Visceral fat (cm2)108.5 (33.7)107.7 (29.4)106.2 (29.4)Waist circumference (cm) 91.0 (12.8)92.4 (9.5)90.9 (10.4)SBP right (mmHg)133.4 (14.8)133.0 (15.9)133.4 (22.4)DBP right (mmHg)73.3 (7.2)76.4 (8.0)72.1 (11.4)RHR (beats/min) 64.3 (10.0)65.3 (8.1)60.8 (7.1)hsCRP (mg/L) 2.2 (3.4)2.9 (5.2)1.8 (1.8)HbA1c (%) 5.6 (0.3)5.6 (0.4)5.5 (0.4)Glucose (mmol/L)5.5 (0.7)5.3 (0.7)5.5 (0.5)HDL (mmol/L) 1.9 (0.6)1.7 (0.3)1.9 (0.5)LDL (mmol/L) 3.5 (1.0)3.3 (0.6)3.3 (0.9)TC (mmol/L) 5.8 (1.1)5.3 (0.9)5.5 (1.1)TG (mmol/L) 0.9 (0.4)0.9 (0.3)0.9 (0.4)Diabetes (%No)97.5100.090.3VO2peak (mL/kg/min)31.9 (7.0)31.9 (5.4)32.3 (6.5)VO2peak or VO2max (%VO2max)#73.755.080.0Grip strength (kg)33.5 (11.8)38.1 (10.3)37.2 (9.4)Sleep index (total score)5.2 (1.4)5.2 (1.9)4.7 (1.2)SF-8 Physical health54.1 (5.3)48.0 (9.7)52.0 (7.2)SF-8 Mental health55.7 (5.0)54.6 (5.6)56.3 (3.8)HADSb (total score)4.8 (3.8)5.8 (4.7)4.0 (3.2)# Percentage of participants that achieved VO2max during the graded maximal exercise testing.The continuous measures are shown as mean and standard deviation in the parentheses. Categorical data is reported as percentages. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; RHR: resting heart rate; hsCRP: high sensitivity C-reactive protein; HbA1c: glycated hemoglobin; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TC: total cholesterol; TG: triglycerides; SF-8: short form health survey questionnaire; HADS: Hospital Anxiety and Depression Scale.Supplementary Table 3. Demographics and clinical data for control, MICT and HIIT participants at the 3-year examinationControl(N=39)MICT(N=21)HIIT(N=30)Women (%) 51.352.446.7Living with others (%Yes) 62.277.873.3Education %Primary school5.114.36.9 %High school30.814.317.2 %University64.171.475.9Smoking (%No)89.294.493.3Age (years) 74.8 (1.8)74.9 (1.8)75.1 (2.0)Height (cm) 167.6 (9.4)171.0 (8.1)170.1 (8.7)Weight (kg) 72.2 (12.6)76.0 (11.4)75.7 (13.1)Fat (%) 30.6 (7.9)29.7 (8.0)29.5 (6.6)Muscle mass (%) 37.6 (5.0)38.4 (4.4)38.6 (3.9)BMI (kg/m2) 25.6 (3.3)26.0 (3.9)26.1 (3.0)Visceral fat (cm2)113.3 (29.8)111.6 (30.5)114.2 (29.6)Waist circumference (cm) 93.7 (11.6)94.3 (10.2)93.1 (10.1)SBP right (mmHg)135.2 (15.6)130.0 (17.1)131.2 (21.2)DBP right (mmHg)73.2 (8.1)75.6 (9.9)72.9 (10.2)RHR (beats/min) 61.2 (8.9)63.6 (10.5)59.9 (6.8)hsCRP (mg/L) 3.4 (9.8)1.9 (2.4)2.6 (4.7)HbA1c (%) 5.4 (0.3)5.5 (0.6)5.5 (0.5)Glucose (mmol/L)5.5 (0.6)5.4 (0.8)5.5 (0.6)HDL (mmol/L) 2.0 (0.6)1.7 (0.5)1.9 (0.7)LDL (mmol/L) 3.8 (1.0)3.1 (0.6)3.3 (1.0)TC (mmol/L) 6.0 (1.2)5.2 (0.7)5.5 (1.2)TG (mmol/L) 0.9 (0.5)1.0 (0.5)1.0 (0.4)Diabetes (%No)97.388.989.7VO2peak (mL/kg/min)31.3 (8.0)29.7 (6.2)31.8 (7.3)VO2peak or VO2max (%VO2max)#66.752.972.4Grip strength (kg)28.0 (10.4)32.3 (10.5)30.8 (10.0)Sleep index (total score)5.3 (1.5)5.4 (1.6)4.7 (1.1)SF-8 Physical health52.3 (6.3)49.5 (8.7)52.6 (5.4)SF-8 Mental health55.2 (5.1)54.3 (6.4)57.6 (2.2)HADS (total score)5.4 (4.1)5.4 (5.0)4.3 (2.6)# Percentage of participants that achieved VO2max during the graded maximal exercise testing.The continuous measures are shown as mean and standard deviation in the parentheses. Categorical data is reported as percentages. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; RHR: resting heart rate; hsCRP: high sensitivity C-reactive protein; HbA1c: glycated hemoglobin; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TC: total cholesterol; TG: triglycerides; SF-8: short form health survey questionnaire; HADS: Hospital Anxiety and Depression Scale. Supplementary Table 4. Demographics and clinical data for control, MICT and HIIT participants at the 5-year examinationControl(N=35)MICT(N=21)HIIT(N=29)Women (%) 48.652.444.8Living with others (%Yes) 68.878.972.0Education %Primary school2.914.37.1 %High school31.414.317.9 %University65.771.475.0Smoking (%No)87.594.792.0Age (years) 76.6 (1.7)76.9 (1.8)77.1 (2.0)Height (cm) 168.7 (10.5)170.0 (8.2)168.6 (7.9)Weight (kg) 74.0 (15.0)75.1 (10.8)74.1 (11.5)Fat (%) 30.8 (8.3)31.5 (7.6)30.0 (5.9)Muscle mass (%) 37.6 (4.9)37.3 (4.2)38.0 (3.4)BMI (kg/m2) 25.9 (3.8)26.0 (3.6)26.0 (2.5)Visceral fat (cm2)117.6 (36.2)116.5 (29.8)115.8 (26.1)Waist circumference (cm) 94.2 (12.9)94.8 (8.9)94.7 (11.1)SBP/DBP right (mmHg) 135.8 (17.7)132.6 (18.7)136.4 (19.1)DBP right (mmHg) 77.0 (7.3)76.7 (13.0)75.3 (11.5)RHR (beats/min) 61.6 (8.5)62.3 (6.2)60.4 (8.3)hsCRP (mg/L) 3.8 (5.8)2.2 (3.7)2.8 (4.9)HbA1c (%) 5.3 (0.3)5.5 (0.5)5.4 (0.5)Glucose (mmol/L)5.3 (0.4)5.4 (1.1)5.4 (0.6)HDL (mmol/L) 1.7 (0.5)1.7 (0.5)1.8 (0.5)LDL (mmol/L) 3.3 (1.1)2.8 (0.9)3.2 (0.8)TC (mmol/L) 5.6 (1.1)4.9 (1.0)5.6 (0.9)TG (mmol/L) 1.0 (0.4)0.9 (0.4)1.0 (0.4)Diabetes (%No)100.089.592.3VO2peak (mL/kg/min)30.1 (7.6)28.6 (5.3)30.5 (6.1)VO2peak or VO2max (%VO2max)#77.455.670.8Grip strength (kg)28.4 (10.1)29.4 (10.0)30.3 (10.4)Sleep index (total score)5.4 (1.4)5.6 (1.9)5.1 (1.3)SF-8 Physical health51.0 (7.7)48.2 (9.1)51.5 (7.8)SF-8 Mental health56.0 (5.0)53.5 (7.5)57.2 (2.0)HADS (total score)6.0 (3.6)5.9 (5.1)4.0 (3.3)MoCA (total score)25.6 (2.7)26.6 (3.3)26.4 (2.8)# Percentage of participants that achieved VO2max during the graded maximal exercise testing.The continuous measures are shown as mean and standard deviation in the parentheses. Categorical data is reported as percentages. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; RHR: resting heart rate; hsCRP: high sensitivity C-reactive protein; HbA1c: glycated hemoglobin; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TC: total cholesterol; TG: triglycerides; SF-8: short form health survey questionnaire; HADS: Hospital Anxiety and Depression Scale; MoCA: Montreal Cognitive Assessment.Supplementary Table 5. Adherence to physical activity guideline for the control, and to the MICT and HIIT intervention for the MICT and HIIT groups given as number of participants (%) fulfilling the adherence requirementsControlMICTHIIT1 yearN=42N=21N=3138 (90.5%)16 (76.2%)23 (74.2%)3 yearsN=39N=21N=3032 (82.1%)15 (71.4%)26 (86.7%)5 yearsN=35N=21N=2933 (94.3%)18 (85.7%)23 (79.3%)MICT: Moderate intensity continuous training; HIIT: High intensity interval training. Adherence to the control was defined as ≥ 75 minutes of physical activity per week; as Adherence to MICT: ≥ 30 minutes at 11-14 on the Borg scale per week; as Adherence to HIIT: ≥ 30 minutes ≥ 15 on the Borg scale per week Supplementary Table 6. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention (Model 1) in HIIT and MICT groups compared to control group?HeadBodyTailCA1CA3DGCIpCIpCIpCIpCIpCIp1 year * MICT0.01-0.02,0.040.630.01-0.01,0.030.330.01-0.01,0.030.312.68-5.94,11.300.541.59-3.14,6.320.510.53-3.18,4.240.783 years * MICT-0.00-0.03,0.030.98-0.01-0.03,0.020.510.01-0.01,0.030.38-0.96-9.86,7.940.831.96-2.93,6.840.430.74-3.09,4.570.715 years * MICT-0.02-0.05,0.020.290.01-0.02,0.030.590.01-0.01,0.040.15-2.22-11.01,6.580.621.33-3.50,6.160.592.16-1.63,5.950.261 year * HIIT-0.00-0.03,0.030.89-0.01-0.03,0.010.27-0.01-0.03,0.010.37-7.74-15.48,-0.010.0500.28-3.97,4.520.900.47-2.86,3.800.783 years * HIIT-0.02-0.05,0.010.30-0.03-0.05,-0.010.003-0.01-0.03,0.010.18-11.59-19.53,-3.640.004-1.68-6.04,2.680.45-0.74-4.17,2.680.675 years * HIIT-0.02-0.05,0.010.16-0.02-0.04,0.000.09-0.01-0.02,0.010.52-12.85-20.90,-4.800.002-4.40-8.82,0.020.06-1.27-4.74,2.200.471 year-0.01-0.03,0.010.43-0.01-0.02,0.010.27-0.01-0.02,0.000.242.04-2.90,6.980.42-1.33-4.04,1.380.34-2.14-4.27,-0.020.0483 years-0.02-0.04,-0.000.038-0.01-0.02,0.010.42-0.01-0.02,0.000.222.40-2.68,7.480.36-1.00-3.79,1.790.48-2.84-5.03,-0.650.0115 years-0.02-0.04,-0.000.017-0.03-0.05,-0.02<0.001-0.02-0.03,-0.010.0053.04-2.20,8.290.260.12-2.76,3.000.94-4.28-6.54,-2.02<0.001p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Volumes of the long axis are included in the model as mL, the subfields are reported as mm3. CA1=cornus ammonis 1; CA3=cornus ammonis 3; DG=dentate gyrus. Head, body and tail are from the long-axis, while CA1, CA3 and DG are from the subfields. HIIT: High intensity interval training; MICT: Moderate intensity continuous training. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 7. Linear mixed model analyses of brain volumes during 5 years of intervention, corrected for CRF (Model 2), in HIIT and MICT groups compared to control group?HippocampusCaudateThalamusCortexWhite matterCIpCIpCIpCIpCIp1 year * MICT0.03-0.07,0.130.540.02-0.09,0.130.710.00-0.11,0.110.950.34-5.03,5.700.90-5.79-15.71,4.120.253 years * MICT-0.07-0.18,0.040.19-0.02-0.14,0.100.69-0.11-0.23,0.010.07-5.41-11.23,0.420.07-1.08-11.80,9.640.845 years * MICT-0.08-0.19,0.020.12-0.04-0.15,0.080.55-0.17-0.29,-0.060.004-1.02-6.70,4.660.720.44-10.02,10.910.931 year * HIIT0.01-0.07,0.100.78-0.02-0.11,0.080.75-0.03-0.13,0.060.51-3.25-7.89,1.400.172.85-5.71,11.410.513 years * HIIT-0.09-0.18,0.000.06-0.06-0.16,0.040.23-0.09-0.19,0.010.08-4.14-9.08,0.800.105.95-3.13,15.040.205 years * HIIT-0.10-0.20,-0.010.034-0.01-0.12,0.090.80-0.08-0.18,0.030.15-1.01-6.11,4.100.70-0.58-9.95,8.800.901 year-0.10-0.15,-0.040.001-0.09-0.15,-0.020.007-0.14-0.20,-0.08<0.001-3.57-6.63,-0.500.0220.53-5.07,6.130.853 years-0.16-0.22,-0.10<0.001-0.10-0.17,-0.040.002-0.25-0.32,-0.18<0.001-4.72-8.02,-1.420.005-3.29-9.32,2.750.295 years-0.31-0.37,-0.25<0.001-0.21-0.28,-0.14<0.001-0.50-0.57,-0.44<0.001-20.67-24.03,-17.31<0.001-5.05-11.19,1.090.11CRF0.00-0.00,0.010.170.00-0.01,0.010.870.00-0.00,0.010.310.04-0.24,0.330.770.20-0.35,0.750.47p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Brain volumes are included in the model as mL. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; CRF: Cardiorespiratory fitness measured as VO2peak. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 8. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention, corrected for CRF (Model 2), in HIIT and MICT groups compared to control group?HeadBodyTailCA1CA3DGCIpCIpCIpCIpCIpCIp1 year * MICT0.01-0.02,0.050.520.01-0.01,0.040.370.01-0.01,0.030.353.73-4.97,12.420.401.53-2.95,6.010.500.44-3.26,4.130.823 years * MICT0.01-0.03,0.040.70-0.00-0.03,0.020.770.01-0.01,0.030.49-1.30-10.70,8.090.793.67-1.17,8.510.140.75-3.25,4.740.715 years * MICT-0.01-0.05,0.020.510.01-0.02,0.030.500.01-0.01,0.040.23-0.26-9.44,8.910.961.06-3.67,5.790.662.08-1.82,5.980.301 year * HIIT-0.00-0.03,0.030.86-0.01-0.03,0.010.34-0.01-0.03,0.010.38-7.45-15.03,0.130.060.65-3.25,4.560.740.61-2.61,3.830.713 years * HIIT-0.01-0.04,0.020.39-0.03-0.05,-0.010.007-0.01-0.03,0.010.41-11.88-19.93,-3.840.004-1.91-6.05,2.240.37-1.48-4.90,1.930.405 years * HIIT-0.02-0.06,0.010.17-0.02-0.04,0.010.18-0.01-0.03,0.010.45-13.36-21.68,-5.050.002-4.91-9.20,-0.620.025-0.41-3.94,3.130.821 year-0.01-0.03,0.010.36-0.01-0.02,0.000.18-0.01-0.02,0.000.261.67-3.23,6.580.50-1.49-4.02,1.040.25-2.36-4.44,-0.270.0273 years-0.02-0.04,-0.000.040-0.01-0.02,0.010.33-0.01-0.02,0.000.063.29-2.00,8.570.22-1.00-3.72,1.720.47-2.34-4.59,-0.100.0415 years-0.02-0.04,-0.000.036-0.03-0.05,-0.02<0.001-0.02-0.03,-0.000.0073.66-1.72,9.040.180.36-2.41,3.130.80-4.29-6.57,-2.00<0.001CRF0.00-0.00,0.000.420.00-0.00,0.000.48-0.00-0.00,0.000.860.08-0.41,0.570.75-0.07-0.32,0.180.590.09-0.12,0.300.40p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table, 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Volumes of the long axis are included in the model as mL, the subfields are reported as mm3. CA1=cornus ammonis 1; CA3=cornus ammonis 3; DG=dentate gyrus. Head, body and tail are from the long-axis, while CA1, CA3 and DG are from the subfields. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; CRF: Cardiorespiratory fitness measures as VO2peak. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 9. Linear mixed model analyses of brain volumes during 5 years of intervention (Model 1) in combined MICT&HIIT group compared to control groupHippocampusCaudateThalamusCortexWhite matterCIpCIpCIpCIpCIp1year * MICT&HIIT0.01-0.07,0.090.83-0.01-0.09,0.080.86-0.02-0.11,0.060.61-2.24-6.40,1.920.29-0.03-7.33,7.270.993 years * MICT&HIIT-0.07-0.15,0.010.10-0.05-0.13,0.040.28-0.08-0.17,0.000.06-4.39-8.68,-0.100.044.33-3.18,11.840.265 years * MICT&HIIT-0.11-0.19,-0.020.01-0.04-0.13,0.050.36-0.11-0.20,-0.020.01-1.32-5.66,3.020.551.24-6.36,8.840.751 year-0.09-0.15,-0.030.002-0.09-0.15,-0.030.01-0.13-0.20,-0.07<0.001-3.46-6.57,-0.350.030.45-4.95,5.850.873 years-0.18-0.24,-0.12<0.001-0.12-0.18,-0.05<0.001-0.26-0.32,-0.19<0.001-4.99-8.19,-1.790.002-4.00-9.55,1.560.165 years-0.32-0.38,-0.25<0.001-0.20-0.27,-0.14<0.001-0.52-0.59,-0.45<0.001-20.41-23.71,-17.10<0.001-6.03-11.76,-0.290.04p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Brain volumes are included in the model as mL. MICT: Moderate intensity continuous training; HIIT: High intensity interval training. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 10. Linear mixed model analyses of brain volumes during 5 years of intervention, corrected for CRF (Model 2), in combined MICT&HIIT group compared to control group ?HippocampusCaudateThalamusCortexWhite matterCIpCIpCIpCIpCIp1 year * MICT&HIIT0.02-0.06,0.090.61-0.00-0.08,0.080.99-0.02-0.10,0.070.68-1.88-6.00,2.240.37-0.55-8.17,7.070.893 years * MICT&HIIT-0.08-0.16,-0.000.04-0.05-0.14,0.040.30-0.10-0.19,-0.010.04-4.58-9.00,-0.150.043.33-4.85,11.510.435 years * MICT&HIIT-0.09-0.18,-0.010.02-0.02-0.12,0.070.61-0.12-0.21,-0.030.01-1.11-5.59,3.370.630.11-8.16,8.390.981 year-0.10-0.15,-0.040.001-0.09-0.15,-0.020.01-0.14-0.20,-0.08<0.001-3.61-6.69,-0.520.020.58-5.09,6.240.843 years-0.16-0.22,-0.10<0.001-0.10-0.17,-0.040.002-0.25-0.32,-0.18<0.001-4.72-8.04,-1.390.01-3.28-9.39,2.820.295 years-0.31-0.37,-0.25<0.001-0.21-0.28,-0.14<0.001-0.50-0.57,-0.44<0.001-20.63-24.01,-17.24<0.001-5.09-11.30,1.120.11CRF0.00-0.00,0.010.160.00-0.01,0.010.840.00-0.00,0.010.240.07-0.21,0.360.620.17-0.38,0.720.55p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Brain volumes are included in the model as mL. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; CRF: Cardiorespiratory fitness measured as VO2peak. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 11. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention (Model 1) in combined MICT&HIIT group compared to control group HeadBodyTailCA1CA3DGCIpCIpCIpCIpCIpCIp1 year * MICT&HIIT0.00-0.02,0.030.87-0.00-0.02,0.020.82-0.00-0.02,0.020.95-3.43-10.21,3.350.320.81-2.91,4.520.670.48-2.42,3.390.743 years * MICT&HIIT-0.01-0.04,0.020.47-0.02-0.04,-0.000.02-0.00-0.02,0.010.67-7.20-14.19,-0.220.04-0.17-4.00,3.650.93-0.12-3.12,2.870.945 years * MICT&HIIT-0.02-0.05,0.010.13-0.01-0.03,0.010.400.00-0.01,0.020.74-8.37-15.43,-1.310.02-1.93-5.80,1.940.330.22-2.81,3.240.891 year-0.01-0.03,0.010.43-0.01-0.02,0.010.27-0.01-0.02,0.000.242.04-2.96,7.030.42-1.33-4.06,1.410.34-2.14-4.28,-0.010.043 years-0.02-0.04,-0.000.04-0.01-0.02,0.010.42-0.01-0.02,0.000.232.40-2.74,7.530.36-1.00-3.82,1.810.49-2.84-5.04,-0.640.015 years-0.02-0.04,-0.000.02-0.03-0.05,-0.02<0.001-0.02-0.03,-0.010.013.04-2.26,8.340.260.12-2.79,3.020.94-4.28-6.55,-2.00<0.001p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Volumes of the long axis are included in the model as mL, the subfields are reported as mm3. CA1=cornus ammonis 1; CA3=cornus ammonis 3; DG=dentate gyrus. Head, body and tail are from the long-axis, while CA1, CA3 and DG are from the subfields. MICT: Moderate intensity continuous training; HIIT: High intensity interval training. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 12. Linear mixed model analyses of the hippocampal long-axis and subfield volumes during 5 years of intervention, corrected for CRF (Model 2) in combined MICT&HIIT group compared to control group HeadBodyTailCA1CA3DGCIpCIpCIpCIpCIpCIp1 year * MICT&HIIT0.00-0.02,0.030.83-0.00-0.02,0.020.85-0.00-0.02,0.010.90-3.05-9.79,3.700.381.00-2.47,4.480.570.55-2.29,3.380.713 years * MICT&HIIT-0.01-0.03,0.020.69-0.02-0.04,-0.000.04-0.00-0.02,0.020.84-7.75-14.99,-0.520.040.21-3.51,3.940.91-0.64-3.68,2.400.685 years * MICT&HIIT-0.02-0.05,0.010.20-0.01-0.03,0.010.570.00-0.02,0.020.90-8.00-15.32,-0.670.03-2.35-6.13,1.420.220.67-2.40,3.750.671 year-0.01-0.03,0.010.36-0.01-0.02,0.000.18-0.01-0.02,0.000.261.65-3.34,6.630.52-1.46-4.03,1.110.27-2.34-4.43,-0.240.033 years-0.02-0.04,-0.000.04-0.01-0.02,0.010.33-0.01-0.02,0.000.063.29-2.08,8.650.23-1.00-3.76,1.770.48-2.34-4.60,-0.090.045 years-0.02-0.04,-0.000.04-0.03-0.05,-0.02<0.001-0.02-0.03,-0.000.0073.68-1.78,9.150.190.33-2.48,3.150.82-4.31-6.60,-2.01<0.001CRF0.00-0.00,0.000.420.00-0.00,0.000.47-0.00-0.00,0.000.890.10-0.40,0.590.70-0.09-0.35,0.160.470.08-0.13,0.280.48p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. Volumes of the long axis are included in the model as mL, the subfields are reported as mm3. CA1=cornus ammonis 1; CA3=cornus ammonis 3; DG=dentate gyrus. Head, body and tail are from the long-axis, while CA1, CA3 and DG are from the subfields. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; CRF: Cardiorespiratory fitness measures as VO2peak. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.Supplementary Table 13. Linear mixed model analyses with CRF as dependent variable during 5 years of intervention in control, MICT and HIIT groupsCIp-valueControl as reference1 year * MICT0.79-1.28, 2.870.463 years * MICT-0.50-2.71, 1.720.665 years * MICT-0.01-2.23, 2.200.991 year * HIIT0.21-1.61, 2.030.823 years * HIIT1.07-0.85, 2.990.275 years * HIIT0.98-1.05, 3.000.341 year1.330.12, 2.540.033 years0.06-1.26, 1.370.935 years-1.29-2.64, 0.050.06MICT as reference1 year * Controls-0.79-2.87, 1.280.463 years * Controls-0.50-1.72, 2.710.665 years * Controls0.01-2.20, 2.230.991 year * HIIT-0.58-2.78, 1.620.613 years * HIIT1.57-0.72, 3.870.185 years * HIIT0.99-1.36, 3.340.411 year2.120.39, 3.850.023 years-0.44-2.26, 1.380.645 years-1.30-3.10, 0.500.16HIIT as reference1 year * Controls-0.21-2.03, 1.610.823 years * Controls-1.07-2.99, 0.850.275 years * Controls-0.98-3.00, 1.050.341 year * MICT0.58-1.62, 2.780.613 years * MICT-1.57-3.87, 0.720.185 years * MICT-0.99-3.34, 1.360.411 year1.540.13, 2.950.033 years1.13-0.31, 2.580.135 years-0.32-1.87, 1.240.69p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the reference group. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; CRF: cardiorespiratory fitness measures as VO2peak. The analysis is corrected for age at baseline, sex and education.Supplementary Table 14. Longitudinal linear mixed model analyses with CRF as dependent variable during 5 years of intervention in combined MICT&HIIT group compared to control groupCIp1 year * MICT&HIIT0.44-1.17,2.040.603 years * MICT&HIIIT0.48-1.24,2.190.595 years * MICT&HIIT0.55-1.22,2.320.541 year1.330.11,2.550.033 years0.06-1.26,1.390.935 years-1.29-2.65,0.070.06p-values < 0.05 are in bold font. Single asterisk (*) indicates interaction. Beta () is the estimated regression coefficient, CI is the 95% confidence interval. In the table 1 year, 3 years and 5 years are compared to baseline and relative to the control group. MICT: Moderate intensity continuous training; HIIT: High intensity interval training; CRF: cardiorespiratory fitness measures as VO2peak. The analysis is corrected for age at baseline, sex and education.References ADDIN EN.REFLIST 1.Bragantini D, Sivertsen B, Gehrman P, Lydersen S, Güzey IC. Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study. BMC medical genetics. 2019;20(1):1-7.2.Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol. 1997;30(1):260-311.3.Stensvold D, Sandbakk SB, Viken H, et al. Cardiorespiratory reference data in older adults: the generation 100 study. Medicine and science in sports and exercise. 2017;49(11):2206.4.Stensvold D, Viken H, Steinshamn SL, et al. Effect of exercise training for five years on all cause mortality in older adults—the Generation 100 study: randomised controlled trial. BMJ. 2020;371:m3485.5.Borg G. Ratings of perceived exertion and heart rates during short-term cycle exercise and their use in a new cycling strength test. Int J Sports Med. 1982;3(3):153-158. ................
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