Effect of 5 Years of Exercise Intervention at Different Intensities on Brain Structure in Older Adults from the General Population: A Generation 100 Substudy

Figures & data

Figure 1 Flowchart describing the process of inclusion into the study and the intervention period. Number (N) of participants at each time point and reasons for exclusion; failed MRI processing (eg due to excessive movement), death and percentages (%) of withdrawal at baseline and after 1, 3 and 5 years of intervention for the MRI study are provided.

Table 1 Demographics and Clinical Data for the Control, MICT and HIIT Participants Undergoing Brain MRI at Baseline

	Control (N=48)	MICT (N=24)	HIIT (N=33)	p-value
Women^a (%)	52.1	54.2	42.4	0.61
Living with others^a (%Yes)	68.8	70.8	71.9	0.95
Education^b %Primary school	8.3	12.5	6.2	0.50
%High school	33.3	20.8	21.9
%University	58.3	66.7	71.9
Smoking^a (%No)	89.6	95.7	90.6	0.69
Age^c (years)	72.0 (1.8)	71.8 (1.7)	72.3 (2.1)	0.54
Height^c (cm)	169.0 (9.7)	171.6 (7.5)	170.8 (8.7)	0.44
Weight^c (kg)	74.1 (13.2)	75.7 (9.9)	76.5 (13.6)	0.70
Fat^c (%)	30.3 (8.0)	29.5 (7.8)	28.2 (7.1)	0.49
Muscle mass^c (%)	38.1 (4.8)	38.6 (4.5)	39.2 (4.1)	0.56
BMI^c (kg/m^2)	25.9 (3.3)	25.9 (3.4)	26.1 (3.3)	0.96
Visceral fat^c (cm^2)	113.3 (32.1)	111.2 (32.8)	112.2 (31.1)	0.96
Waist circumference^c (cm)	93.3 (11.0)	93.5 (9.2)	94.4 (11.3)	0.90
SBP right^c (mmHg)	135.4 (17.5)	132.3 (14.0)	133.0 (18.8)	0.72
DBP right^c (mmHg)	74.2 (8.2)	77.4 (8.7)	75.6 (8.7)	0.33
RHR^c (beats/min)	63.4 (9.0)	65.0 (8.9)	62.9 (10.4)	0.71
hsCRP^b (mg/L)	1.5 (1.1)	2.1 (3.8)	3.0 (5.0)	0.43
HbA1c^b (%)	5.6 (0.3)	5.6 (0.3)	5.6 (0.5)	0.71
Glucose^c (mmol/L)	5.6 (0.6)	5.4 (0.7)	5.6 (0.8)	0.12
HDL^c (mmol/L)	1.9 (0.6)	1.8 (0.5)	1.9 (0.7)	0.85
LDL^c (mmol/L)	3.6 (1.0)	3.2 (0.7)	3.3 (1.0)	0.15
TC^c (mmol/L)	5.9 (1.1)	5.5 (0.6)	5.7 (1.1)	0.15
TG^c (mmol/L)	1.0 (0.4)	1.0 (0.4)	1.1 (0.6)	0.87
Diabetes^a (%No)	100.0	100.0	93.5	0.10
VO2peak^c (mL/kg/min)	30.3 (6.6)	30.0 (5.7)	30.4 (6.9)	0.97
VO2peak or VO2max (%VO2max)^a,#	64.6	52.2	75.8	0.19
Grip strength^c (kg)	34.5 (10.9)	35.4 (10.8)	37.9 (9.4)	0.35
Sleep index^c (total score)	5.1 (1.5)	5.6 (1.7)	4.9 (1.5)	0.27
SF-8 Physical health^b	54.2 (5.5)	51.9 (5.2)	51.7 (6.7)	0.11
SF-8 Mental health^b	55.0 (4.2)	55.4 (4.9)	55.9 (4.3)	0.66
HADS^c (total score)	4.5 (3.5)	4.7 (4.4)	4.5 (3.1)	0.98

Notes: The continuous measures are shown as mean and standard deviation in the parentheses. Categorical data is reported as percentages. ^aChi-squared test; ^bKruskal–Wallis test; ^cone-way ANOVA. ^#Percentage of participants that achieved VO_2max during the graded maximal exercise testing.

Abbreviations: 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.

Table 2 Linear Mixed Model Analyses of Brain Volumes During 5 Years of Intervention (Model 1) in HIIT and MICT Group Compared to Control Group

	Hippocampus			Caudate			Thalamus			Cortex			White Matter
	β	CI	p	β	CI	p	β	CI	p	β	CI	p	β	CI	p
1 year * MICT	0.01	−0.09, 0.11	0.83	0.00	−0.11, 0.11	0.97	−0.01	−0.12, 0.10	0.91	−0.68	−6.02, 4.66	0.80	−4.72	−14.05, 4.61	0.32
3 years * MICT	−0.05	−0.16, 0.05	0.32	−0.04	−0.16, 0.07	0.46	−0.09	−0.20, 0.03	0.13	−5.47	−10.99, 0.05	0.06	0.56	−9.08, 10.20	0.91
5 years * MICT	−0.09	−0.19, 0.01	0.09	−0.05	−0.16, 0.07	0.42	−0.13	−0.25, −0.02	0.021	−1.49	−6.95, 3.97	0.59	1.16	−8.36, 10.69	0.81
1 year * HIIT	0.01	−0.08, 0.10	0.87	−0.01	−0.11, 0.08	0.77	−0.03	−0.13, 0.06	0.50	−3.32	−8.07, 1.43	0.17	3.19	−5.10, 11.48	0.45
3 years * HIIT	−0.08	−0.17, 0.02	0.10	−0.05	−0.15, 0.05	0.31	−0.08	−0.18, 0.02	0.12	−3.65	−8.53, 1.23	0.14	6.85	−1.66, 15.36	0.12
5 years * HIIT	−0.12	−0.21, −0.03	0.012	−0.04	−0.14, 0.06	0.46	−0.10	−0.20, 0.00	0.06	−1.16	−6.11, 3.79	0.65	1.11	−7.52, 9.74	0.80
1 year	−0.09	−0.15, −0.03	0.002	−0.09	−0.15, −0.03	0.005	−0.13	−0.20, −0.07	<0.001	−3.46	−6.55, −0.37	0.028	0.44	−4.91, 5.80	0.87
3 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	−8.18, −1.81	0.002	−4.00	−9.51, 1.51	0.15
5 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	−23.70, −17.12	<0.001	−6.03	−11.72, −0.34	0.038

Notes: p-values <0.05 are in bold font. Single asterisk (*) indicates interaction. Beta (β) 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. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.

Abbreviations: HIIT, high intensity interval training; MICT, moderate intensity continuous training.

Figure 2 Mean and 95% CI for total hippocampal, cortex, thalamus, caudate and white matter volumes (mL) adjusted for ICV at each time point in the control (grey circle), moderate intensity continuous training (MICT) (orange triangle) or high intensity interval training (HIIT) (blue square) groups. See Table 2 and Supplementary Table 7 for results of statistical comparisons.

Figure 3 Mean and 95% CI for CRF, objectively measured as VO_2peak, at each time point in the control (grey circle), moderate intensity continuous training (MICT) (orange triangle) and high intensity interval training (HIIT) (blue square) groups. See Supplementary Table 13 for results of statistical comparisons.

Table 3 Linear Regressions Predicting Brain Volumes Across All Participants After 1, 3 and 5 Years of Intervention Based on Baseline CRF

	Hippocampus			Thalamus			Caudate			Cortex			White Matter
	β	CI	p	β	CI	p	β	CI	p	β	CI	p	β	CI	p
1 year
CRF at baseline	0.02	−0.00, 0.05	0.055	0.00	−0.03, 0.03	0.796	0.01	−0.02, 0.04	0.599	1.47	0.67, 2.28	<0.001	−1.52	−4.16, 1.12	0.256
3 years
CRF at baseline	0.02	−0.00, 0.05	0.085	−0.00	−0.03, 0.03	0.867	0.01	−0.02, 0.04	0.651	1.16	0.33, 2.00	0.007	−1.14	−3.90, 1.61	0.411
5 years
CRF at baseline	0.02	−0.01, 0.05	0.112	0.00	−0.03, 0.03	0.899	0.01	−0.02, 0.04	0.576	1.17	0.31, 2.04	0.009	−0.87	−3.84, 1.92	0.564

Notes: p-values <0.05 are in bold font. Beta (β) is the estimated regression coefficient, CI is the 95% confidence interval. Brain volumes are included in the model as mL. The analysis is corrected for age at baseline, sex and education. Brain volumes were corrected for intracranial volume (ICV) using the residual method.

Abbreviation: CRF, cardiorespiratory fitness measured as VO_2peak.