Physiological Reports. 2022;10:e15158. 
 
  | 1 of 14
https://doi.org/10.14814/phy2.15158
wileyonlinelibrary.com/journal/phy2
Received: 2 December 2021 | Accepted: 7 December 2021
DOI: 10.14814/phy2.15158  
O R I G I N A L  A R T I C L E
Aerobic exercise training in older men and women— 
Cerebrovascular responses to submaximal exercise: Results 
from the Brain in Motion study
Sonja L. Lake1,2,3 |   Veronica Guadagni1,2,4,5 |   Karen D. Kendall1,3 |   
Michaela Chadder1,3 |   Todd J. Anderson6,7 |   Richard Leigh8 |   Jean M. Rawling9 |   
David B. Hogan2,4,5,8,10,11 |   Michael D. Hill2,4,7,10 |   Marc J. Poulin1,2,4,5,7,12,13
1Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
2Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
3Clinical & Translational Exercise Physiology Lab, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
4Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
5O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
6Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, 
Canada
7Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
8Department of Medicine, University of Calgary, Calgary, Alberta, Canada
9Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada
10Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
11Division of Geriatric Medicine, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
12Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
13Brenda Strafford Foundation Chair in Alzheimer Research, Calgary, Alberta, Canada
This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided 
the original work is properly cited.
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
Sonja L. Lake and Veronica Guadagni are equally contributing first authors. 
Correspondence
Marc J. Poulin, Laboratory of Human 
Cerebrovascular Physiology, Hotchkiss 
Brain Institute, Cumming School 
of Medicine, University of Calgary, 
Room 210 -  Heritage Medical Research 
Building, 3310 Hospital Drive NW, 
Calgary, AB T2N 4N1, Canada.
Email: poulin@ucalgary.ca
Funding information
The Brain in Motion Study is funded 
by Canadian Institutes of Health 
Research (CIHR, MOP142470) and The 
Brenda Strafford Foundation Chair 
in Alzheimer Research (BSFCAR). 
S.L. was supported by an Alberta 
Innovates Summer Studentship. V.G. 
Abstract
Physical inactivity is a leading modifiable risk factor for cardiovascular and cer-
ebrovascular disease, cognitive dysfunction, and global mortality. Regular exer-
cise might mitigate age- related declines in cardiovascular and cerebrovascular 
function. In this study, we hypothesize that a 6- month aerobic exercise interven-
tion will lead to a decrease in cerebrovascular resistance index (CVRi) and to 
an increase in cerebral blood flow (CBF) and cerebrovascular conductance index 
(CVCi) during two submaximal exercise workloads (40% VO2max and 65 W), in-
tensities that have been shown to be comparable to activities of daily life. Two 
hundred three low- active healthy men and women enrolled in the Brain in 
Motion study, completed a 6- month exercise intervention and underwent sub-
maximal and maximal tests pre- /post- intervention. The intervention improved 
2 of 14 |   
LAKE et al.
1 | INTRODUCTION
Declines in cerebral blood flow (CBF) often observed with 
advancing age are considered to be an important contrib-
utor to cognitive decline, as well as cardiovascular and 
cerebrovascular diseases (Leeuwis et al., 2018). These 
declines in CBF are observed at rest and in response to 
various challenges (Tarumi & Zhang, 2018) and they are 
thought to reflect a decline in cerebrovascular reserve, a 
term used to describe “the ability of cerebral blood vessels 
to respond to increased metabolic demand and chemical, 
mechanical, or neural stimuli” (Davenport et al., 2012). 
Accordingly, an increase in blood flow to the brain is war-
ranted when demand is increased, with relatively little en-
suing change in cerebral blood pressure (Ogoh & Ainslie, 
2009; Paulson et al., 1990; Silverman and Petersen, 2021).
Cerebrovascular regulation is a multi- factorial process 
influenced by factors such as the arterial partial pressure of 
CO2 (PaCO2), cerebral metabolism and neurogenic activity, 
cardiac output and mean arterial pressure (MAP) (Ainslie 
& Duffin, 2009; Hoiland et al., 2019; Ogoh & Ainslie, 
2009; Phillips et al., 2016). MAP gradually increases with 
usual aging partially due to arterial stiffening and fibro-
sis (Fontana, 2018; Franklin et al., 1997). Arterial stiffen-
ing leads to a reduced ability of the blood vessels to dilate, 
which can contribute to a further reduction in brain perfu-
sion (i.e., and oxygen delivery). Cerebrovascular resistance 
index (CVRi) and cerebrovascular conductance index 
(CVCi) are traditional indices used to measure the vascular 
tone and the ability of the cerebrovasculature to react to 
stimuli (i.e., increases in arterial PCO2 or blood pressure; 
Joyce et al., 2019; Lautt, 1989). Both indices are metrics of 
vascular tone, but CVRi is normally used when changes 
in tone are primarily driven by changes in pressure, while 
CVCi is used when changes in tone are primarily driven by 
changes in flow (Joyce et al., 2019; Lautt, 1989).
Resting CVRi increases with advancing age as shown 
in a study that compared young control participants to 
older ones (Tarumi & Zhang, 2018). Conversely, CVCi has 
been shown to be decreased in post- menopausal women 
when measured at rest and during moderate- intensity 
submaximal exercise (Brown et al., 2010).
Regular exercise has been shown to mitigate age- related 
declines in cardiovascular and cerebrovascular capacity 
(Kirk- Sanchez & McGough, 2014; Ngandu et al., 2015; 
Pentikäinen et al., 2019; Stensvold et al., 2020). Higher car-
diorespiratory fitness benefits both systemic and cerebral 
circulations, and reduces the adverse neurobiological and 
cognitive consequences of aging, suggesting that regular 
exercise may be protective for the brain and may attenu-
ate the age- related reduction in CBF (Brown et al., 2010; 
Chapman et al., 2013; Franklin et al., 1997; Gajewski & 
Falkenstein, 2016; Guadagni et al., 2020; Huggett et al., 2005; 
Kirk- Sanchez & McGough, 2014; Tarumi & Zhang, 2018). 
In a previous study, Murrell et al. (2013) analyzed changes 
in CBF and cerebrovascular reactivity (i.e., cerebral vascula-
ture response to 5% inspired CO2 [PiCO2]), during both rest 
and submaximal exercise (30% and 70% HRR) before and 
after a 12- week aerobic exercise intervention in both young 
and middle- aged adults. They reported no change in resting 
middle cerebral artery (MCAv) but an increase in cerebro-
vascular reactivity (after correcting for a post- intervention 
decrease in resting end- tidal PCO2). These results suggest a 
beneficial role of exercise training on cerebrovascular func-
tion in middle- aged adults.
was supported by a BRAIN CREATE 
Postdoctoral Fellowship supported by 
The Brenda Strafford Centre on Aging, 
within the O'Brien Institute for Public 
Health, by an Alzheimer Society of 
Canada Postdoctoral Fellowship, and a 
Canadian Institutes of Health Research 
(CIHR) Postdoctoral Fellowship. The 
funders played no role in the concept 
and design of this study, analysis or 
interpretation of the data, or drafting 
and critical revision of the manuscript.
the gas exchange threshold and maximal oxygen consumption (VO2max), with 
no change in heart rate at VO2max, during the treadmill VO2max test. Heart 
rate and CVRi decreased from pre- intervention values during both relative (40% 
VO2max) and absolute (65  W) submaximal exercise tests. Blood flow velocity 
in the middle cerebral artery and CVCi increased post- intervention during 40% 
VO2max and 65 W. Changes in mean arterial pressure were found only during 
the absolute component (65 W). Our study demonstrates that aerobic exercise 
improves not only cardiorespiratory indices but also cerebrovascular function at 
submaximal workloads which may help to mitigate age- related declines in eve-
ryday life. Investigation of the mechanisms underlying the decline in cardiovas-
cular and cerebrovascular capacity with aging has important implications for the 
maintenance of health and continued independence of older adults.
K E Y W O R D S
aerobic exercise intervention, aging, cardiorespiratory fitness, cerebral blood flow, 
cerebrovascular function
   | 3 of 14
LAKE et al.
Previous literature has shown associations between 
declines in CBF and objective parameters of cardiorespi-
ratory fitness such as maximal oxygen uptake (VO2max) 
(Huggett et al., 2005), and increased risk of neurodegener-
ative diseases (Ainslie et al., 2008). The reduction in cardio-
respiratory function (VO2max) and muscular performance 
associated with advancing age and/or inactivity can contrib-
ute to diminished functional capacity (Huggett et al., 2005). 
In low active or sedentary older adults, functional capacity 
can drop to levels lower than the critical functional fitness 
thresholds, which may result in the inability to perform 
daily life activities and reduce independence (Huggett et al., 
2005; Paterson & Warburton, 2010; Taylor, 2014). Indeed, 
studies investigating the VO2 values associated with activi-
ties of daily living have identified cut- off points to predict an 
individual's ability to perform those activities independently 
(Huggett et al., 2005; Morey et al., 1998; Paterson et al., 
1999). For instance, Paterson and colleagues found that 
in adults aged 55– 86 years, the minimum VO2 compatible 
with independent living was 15.4 and 17.7 ml/kg/min for 
women and men, respectively (Paterson et al., 1999). Below 
these cut- offs, individuals were likely to require assistance 
(Paterson et al., 1999). The present study extends the con-
cept proposed by Paterson and colleagues, by evaluating 
cerebrovascular functional capacity at low/moderate exer-
cise intensity below these functional thresholds (Jamnick 
et al., 2020).
This study is an ancillary sub- study of the Brain In 
Motion study (BIM), a quasi- experimental single group 
pre- /post- intervention study (Tyndall et al., 2013). Here, 
we aim to determine in a large sample of healthy seden-
tary older adults the extent to which a 6- month aerobic ex-
ercise intervention is associated with improved objective 
measures of cardiorespiratory and cerebrovascular func-
tions during submaximal exercise at an absolute workload 
of 65  W (i.e., representing a VO2 of approximately 15– 
17 ml/kg/min; Paterson et al., 1999) and a relative inten-
sity that corresponds to 40% VO2max. We hypothesize that 
a 6- month aerobic exercise intervention will lead to a de-
crease in CVRi and to an increase in CBF and CVCi during 
two submaximal workloads (40% VO2max and 65  W). 
These changes will be above and beyond changes in end- 
tidal CO2 (PETCO2). We propose that such improvements 
in cardiovascular and cerebrovascular outcomes after the 
intervention represent increases in functional capacity 
that have implications for daily life activities.
2 | MATERIALS AND METHODS
Healthy but underactive participants were recruited 
through fliers, social media, and world of mouth and pro-
vided informed written consent prior to enrolment. The 
University of Calgary Conjoint Health Research Ethics 
Board provided ethical approval (CHREB: REB 14- 2284). 
The data that support the findings of this study are avail-
able from the corresponding author upon reasonable 
request.
2.1 | Inclusion/exclusion criteria
Participants were required to meet the following criteria 
to be included in the Brain In Motion study: (Tyndall et al., 
2018) (1) age between 50 and 80 years at baseline; (2) re-
porting <30 min of moderate exercise 4 days per week or 
20 min of vigorous exercise 2 days per week; (3) a body 
mass index (BMI) of <35 kg/m2; (4) able to walk indepen-
dently outside as well as up and down at least 20 stairs; 
(5) not diagnosed with clinically evident cardiovascular or 
cerebrovascular disease(s), asthma, type I diabetes melli-
tus and/or another condition that would prevent safe ex-
ercise; (6) acquire a score ≥24 on the Montreal Cognitive 
Assessment (MoCA, Rossetti et al., 2011); (7) non- smoker 
for at least 12 months; (8) no major surgery or trauma in 
the last 6 months; (9) no diagnosis of neurologic disease; 
and, (10) clearance obtained from their attending health 
care professional to participate in the study. Prior to being 
enrolled, participants were assessed by a study physician, 
and their medications were noted. Participants were ex-
cluded from this ancillary study if they did not complete 
the 6- month aerobic exercise intervention or had incom-
plete gas exchange threshold (GET) and VO2max data pre- 
and post- intervention (see “Results” section).
2.2 | Exercise intervention
Participants took part in a supervised 6- month aero-
bic training program that was held three days a week at 
the Fitness Centre in the Faculty of Kinesiology at the 
University of Calgary. Each session included a 5- min 
warm- up, aerobic exercise, a 5- min cool- down, followed 
by stretching. As participants progressed through the ex-
ercise intervention, the duration of aerobic exercise in-
creased from 20 to 40 min. As well, the exercise intensity 
increased from 30%– 45% up to 60%– 70% maximum heart 
rate reserve (HRR) based on individual VO2max results. 
Polar® heart rate monitors were worn by each participant 
throughout the session to ensure compliance to their tar-
get heart rate zones. Heart rate data were collected and 
stored for further analysis using the Polar® Team2 System. 
Participants were considered compliant if they attended 
85% of the total exercise sessions. If a session was missed, 
participants were strongly encouraged to complete an 
unsupervised, “make- up” session independently, which 
4 of 14 |   
LAKE et al.
was recorded using personal workout logbooks. For fur-
ther explanation on the exercise intervention (see Tyndall 
et al., 2013 and Hall et al., 2019).
2.3 | Testing phases
In this report, we focus on data collected immediately 
prior to the start of the intervention (pre- intervention) 
and immediately following the completion of the 6- month 
aerobic exercise intervention (post- intervention). At each 
phase, participants completed a maximal oxygen uptake 
(VO2max) test, and a cerebrovascular function test dur-
ing submaximal exercise during separate visits within 
1– 2  weeks of each other. Several other measurements 
were collected but they are outside the scope of this report. 
For further details, please refer to Tyndall et al. (2013).
2.4 | Cardiorespiratory fitness
Anthropometrics and exercise data were collected in 
the Clinical and Translational Exercise Physiology 
Laboratory, Cumming School of Medicine, University 
of Calgary by Certified Exercise Physiologist (Canadian 
Society of Exercise Physiology). Anthropometric data 
were collected prior to completion of the maximal oxygen 
uptake test and included measurements of participant's 
height, weight, and skin folds. Following, maximal oxy-
gen uptake (VO2max) was determined using a metabolic 
cart (Parvo Medics TruOne 2400). Ventilatory volumes 
and expiratory gases were measured during a ramp 
exercise test on a programmable motorized treadmill 
(Quinton TM55). Baseline ventilatory measures were 
obtained during a three- minute period of quiet stand-
ing on the treadmill. Warm- up measures were obtained 
during a four- minute slow walk at a speed of 1.7 mph 
and a 0% grade. Following the warm- up period, a com-
bination of small increases in velocity and grade that 
occurred every 30 s were used to elicit a ramp- like test 
according to previously described methods (McInnis & 
Balady, 1994). Participants were verbally encouraged 
throughout the test and exercised to volitional fatigue or 
until the appearance of symptoms indicating the need to 
terminate the test according to the American College of 
Sports Medicine's (ACSM) Indications for Terminating 
a Symptom- Limited Maximal Exercise Test (Thompson 
et al., 2010). Recovery measures were obtained for five 
minutes following the test at a speed of 1.7  mph and 
grade at 0%. Heart rate was measured with a 12- lead 
electrocardiogram system (QStress) which monitored 
heart rhythm at rest (5 min) prior to, during, and post- 
exercise (3 min). Exercising heart rate, blood pressure 
(manual brachial measurement), and the participants 
rating of perceived exertion (RPE) value were measured 
every two minutes during exercise. Peak heart rate and 
blood pressure values were recorded at maximal effort. 
VO2max was determined from the highest 30- s average 
value during the exercise test. Ventilatory thresholds 
were determined and verified by two independent inves-
tigators according to the V- slope method (Binder et al., 
2008). In this report on older sedentary adults, we solely 
focused on the GET. With incremental exercise inten-
sity, GET is associated with an increase in lactate follow-
ing which there is a period of isocapnic buffering. At this 
point VCO2  starts to increase out of proportion to the 
increase in VO2 indicating the buffering of lactic acid by 
bicarbonate, but PaCO2 and PETCO2 are relatively stable 
(i.e., there is no respiratory compensation; Beaver et al., 
1986; Poole et al., 2021).
2.5 | Submaximal exercise tests
2.5.1 | Relative workload (40% of 
VO2max) and Absolute workload (65 W)
During the submaximal exercise test, participants were 
seated on a recumbent cycle ergometer (Lode Corival; 
Lode BV Medical Technology). Participants first under-
went ten minutes of resting air breathing to collect base-
line resting end- tidal respiratory values (PETCO2 and 
PETO2) with a dedicated software program (Chamber, 
University Laboratory of Physiology, Oxford, UK) while 
on a mouthpiece connected to a fine capillary attached 
to a mass spectrometer (AMIS 200; Innovision). Then a 
second specialized program (BreatheM v2.40, University 
Laboratory of Physiology, Oxford, UK) was used to accu-
rately and continuously record PETCO2 and PETO2 val-
ues during the exercise tests with no gas manipulation; 
participants for the entire duration of the submaximal 
exercise test simply breathed room air through a mouth-
piece with the nose occluded with a nose clip.
Heart rate was continuously measured throughout the 
submaximal exercise test using a 3- lead electrocardiogram 
system (Micromon 7142 B; Kontron Medical).
Beat- by- beat blood pressure was measured contin-
uously using a finger pulse photoplethysmography 
Finometer (Finapres Finometer Pro; Medical Systems) 
and the finger pressure transducer was positioned at the 
heart level. A sphygmomanometer (Welch Allyn) was also 
used to take brachial measurements during rest.
Arterial hemoglobin saturation was measured using 
finger pulse oximetry (3900p; Datex- Ohmeda).
Blood flow velocity in the MCAv was non- invasively 
measured 
using 
a 
2- MHz 
transcranial 
Doppler 
   | 5 of 14
LAKE et al.
ultrasound 
(TCD) 
(Toc 
NeurovisionTM; 
Multigon 
Industries Inc.; Leeuwis et al., 2018). MCA location 
was determined by placing the TCD probe above the 
zygomatic process near the ear, in the temporal region, 
and using techniques described by Aaslid et al. (1982). 
During the first testing session, the TCD probe was man-
ually moved and the TCD settings of depth, gain, and 
amplitude were optimized to find the best signal from 
the right MCA. Then the probe placement was recorded 
by tracing the location on the side of the head on a trans-
parent sheet together with the TCD settings used. To en-
sure accurate placing of the probe and reliability during 
different sessions the information recorded during the 
first visit was used post- intervention.
In the submaximal exercise test, resting values were 
collected for 5  min before participants started to cycle. 
In the first exercise stage (6 min) participants cycled at a 
work rate relative to 40% of their VO2max values collected 
during the maximal oxygen uptake testing previously de-
scribed. This was followed by a 6- min rest period. In the 
second exercise stage, all participants, regardless of sex, 
cycled at an absolute work rate of 65 W for 6 min. Lastly, 
participants completed 6 min of rest (i.e., recovery phase).
2.6 | Data analyses
2.6.1 | Cerebrovascular measures
The TCD signals were collected every 10 ms and averaged 
values were calculated over each cardiac cycle. Data for 
the last 30- s interval of each phase of the submaximal ex-
ercise test (exercise bouts and rest) were then averaged. 
MCAv values collected and MAP (obtained by the beat- 
by- beat data from the Finometer) were subsequently used 
to calculate CVCi and CVRi:
Data were then analyzed using IBM SPSS Statistics, 
version 25.0 (IBM). Pre- and post- intervention descriptive 
statistics for the sample are reported in Table 1. Paired 
sample t- tests were used to compare data pre- /post- 
intervention. To examine the contribution of changes in 
PETCO2 to changes in MCAv and CVCi from pre-  to post- 
intervention, we used a series of multiple linear regres-
sions with post- scores for MCAv and CVCi (in separate 
models) as dependent variables, pre- scores as predictors 
in block one, and changes in PETCO2 (ΔPETCO2 = post- 
intervention−pre- intervention) as forced confounders. 
We ran these multiple linear regressions for changes pre- /
post- intervention at 40% VO2max and 65  W, separately. 
The advantage of these analyses is that they allow for the 
quantification of how much of the variance is explained 
by changes in PETCO2 by looking at the r2 change of the 
model that considers the covariate.
A value of p < 0.05 was adopted as the minimum level 
of statistical significance, and all analyses were two- tailed. 
A Bonferroni correction for multiple comparisons was 
used with α = 0.05/5 (or 0.01).
3 | RESULTS
3.1 | Subject characteristics
Two hundred eighty- six participants were initially en-
rolled in the study. Two hundred and thirty- six par-
ticipants completed the pre- intervention tests and 206 
completed the 6- month exercise intervention. A detailed 
flowchart of the Brain in Motion study is published else-
where (Guadagni et al., 2020; Hall et al., 2019). In this re-
port, we examine the complete data for 203 participants 
due to missing cardiorespiratory data for three partici-
pants (66.4 ± 6.4 years, MoCA 27.6 ± 1.4, mean years of 
completed education 15.9 ± 2.6, 103 females).
At pre- intervention, 63 participants reported being 
on anti- hypertension medications, 6 participants re-
ported being on anti- hyperglycemic 11 and 42 partici-
pants reports being on lipid- lowering medications. After 
the intervention, 65 participants reported being on anti- 
hypertension medication, 6 participants reported being on 
anti- hyperglycemic and 41 participants reported being on 
lipid- lowering medications. Please refer Table 1 for pre- /
CVRi = [MAP∕MCAv]
CVCi = [MCAv∕MAP]
TABLE 1 Pre- and post- intervention descriptive statistics for 
the sample (n = 203)
Variables
Pre- intervention
Post- 
intervention
Mean
SD
Mean
SD
Age, years
66.4
6.4
67.0
6.4
BMI, kg/m2
26.9
3.7
26.5
3.6
Height, cm
169.3
9.4
169.3
9.4
Weight, kg
77.6
14.4
76.4
14.2
Waist Girth, cm
96.3
11.3
93.1
11.0
MoCA
27.6
1.4
Education, years
15.9
2.6
Biological sex
103 F
100 M
Note: Values are means ± standard deviations (SD); biological sex is 
expressed as a count.
Abbreviations: BMI, body mass index; MoCA, Montreal Cognitive 
Assessment.
6 of 14 |   
LAKE et al.
post- intervention descriptive statistics for select character-
istics of the participants.
3.2 | Cardiorespiratory fitness
The GET increased significantly by 4.6% from pre-  to post- 
intervention (17.78  ±  3.39 vs. 18.64  ±  3.36  ml/kg/min, 
t(202) = −5.99, p < 0.001). VO2max also increased signifi-
cantly by 7.1% from pre- to post- intervention (26.12 ± 5.48 
vs. 28.11 ± 5.86 ml/kg/min, t(202) = −13.27, p < 0.001). No 
significant differences were found in heart rate at VO2max 
from pre-  to post- intervention (see Table 2).
3.3 | Responses to submaximal exercise
3.3.1 | Relative workload (40% of VO2max)
At pre- intervention participants exercised at an average of 
51.0 ± 16.3 W to reach 40% of VO2max. Post- intervention 
the average workload to reach 40% of VO2max increased 
to 55.2 ± 16.9 W, an 8.2% increase.
CVRi decreased by 2.9% from pre- intervention 
(CVRi; 2.15  ±  0.59  mmHg/cm/s) to post- intervention 
(CVRi; 2.09 ± 0.54 mmHg/cm/s), t(199) = 2.47, p = 0.01), 
MCAv increased by 1.9% from pre-  to post- intervention 
(55.8 ± 12.4 vs. 56.9 ± 12.1 cm/s, t(199) = −2.31, p = 0.022) 
and CVCi increased by 2.0% from pre-  to post- intervention 
(0.50 ± 0.14 vs. 0.51 ± 0.14 cm/s/mmHg; t(199) = −2.03, 
p = 0.044). However, the change in CVCi did not remain 
significant after correction for multiple comparisons (see 
Tables 3 and 4 and Figure 1).
No significant changes were observed in MAP during 
relative (40% VO2max) submaximal exercise from pre-  to 
post- intervention. HR significantly decreased by 2.6% from 
pre- intervention (93.2  ±  11.8  bpm) to post- intervention 
(90.9 ± 10.7 bpm), t(202) = 3.82, p < 0.001 (Figure 2).
3.3.2 | Contribution of changes in PETCO2 
to changes in MCAv and CVCi from pre-  to 
post- intervention at relative workload (40% of 
VO2max)
A Multiple Linear Regression on the change in MCAv from 
pre- to post- intervention while controlling for changes in 
PETCO2, showed a significant change in MCAv during 
exercise at a workload of 40% of VO2max from pre- to post- 
intervention (r = 0.827, r2 change = 0.684, p ≤ 0.001) and 
a 3.6% contribution of PETCO2 to this change (model 2: 
r = 0.848, r2 change = 0.036, p ≤ 0.001).
Similarly, the change in CVCi from pre-  to post- 
intervention while controlling for changes in PETCO2, 
showed a significant change in CVCi during exercise at a 
workload of 40% of VO2max from pre- to post- intervention 
(r = 0.763, r2 change = 0.582, p ≤ 0.001) and a 5.4% con-
tribution of PETCO2 to this change (model 2: r = 0.797, r2 
change = 0.054, p ≤ 0.001).
3.3.3 | Absolute workload (65 W)
CVRi decreased significantly by 6.3% from pre- intervention 
to post- intervention (2.37 ± 0.73 vs. 2.23 ± 0.62 mmHg/
cm/s, t(196) = 4.29, p < 0.001). Unlike relative submaxi-
mal exercise, during absolute (65 W) submaximal exercise 
MAP decreased significantly by 3.2% from pre- intervention 
to post- intervention (121.5 ± 20.1 vs. 117.7 ± 17.9 mmHg, 
t(198)  =  3.62, p  <  0.001). MCAv increased significantly 
by 2.1% from pre-  to post- intervention (54.3  ±  12.5 vs. 
55.4 ± 11.9 cm/s, t(196) = −2.07, p = 0.040). However, the 
latter change did not remain significant after correction 
for multiple comparisons. CVCi increased significantly 
by 6.1% from pre-  to post- intervention (0.46  ±  0.14 vs. 
0.49 ± 0.14 cm/s/mmHg, t(196) = −3.78, p < 0.001). Please 
refer to Tables 3 and 4, and Figure 1. HR significantly de-
creased by 4.6% from pre- intervention to post- intervention 
Variables
Pre- intervention
Post- intervention
Mean
SD
Mean
SD
Significance
GET, ml/kg/min
17.78
3.39
18.64
3.36
<0.001
GET, L/min
1.377
0.359
1.422
0.362
<0.001
HRGET, bpm
120.0
17.0
118.5
15.3
<0.001
VO2max, ml/kg/min
26.12
5.48
28.11
5.86
<0.001
VO2max, L/min
2.029
0.569
2.150
0.598
<0.001
HRmax, bpm
154.9
14.1
156.7
14.6
0.095
RER
1.19
0.09
1.19
0.08
<0.001
Note: Values are means ± standard deviation (SD).
Abbreviations: GET, gas exchange threshold; HRGTE, heart rate at GET; HRmax, heart rate at maximal 
oxygen uptake; RER, respiratory exchange ratio; VO2max, maximal oxygen uptake.
TABLE 2 Pre- and post- intervention 
cardiorespiratory data for all participants
   | 7 of 14
LAKE et al.
(104.9 ± 16.5 vs. 100.2 ± 15.2 bpm), t(199) = 6.34, p < 0.001 
(Figure 2).
3.3.4 | Contribution of changes in PETCO2 to 
changes in MCAv and CVCi from pre-  to post- 
intervention at absolute workload (65 W)
A multiple linear regression on the change in MCAv from 
pre- to post- intervention while controlling for changes in 
PETCO2, showed a significant change in MCAv during ex-
ercise at a workload of 65 W from pre- to post- intervention 
(r = 0.801, r2 change = 0.641, p ≤ 0.001) and a 3.4% con-
tribution of PETCO2 to this change (model 2: r = 0.822, r2 
change = 0.034, p ≤ 0.001).
Similarly, the change in CVCi from pre-  to post- 
intervention while controlling for changes in PETCO2, 
showed a significant change in CVCi during exercise 
at a workload of 65  W from pre-  to post- intervention 
(r = 0.761, r2 change = 0.580, p ≤ 0.001) and a 2.3% con-
tribution of PETCO2 to this change (model 2: r = 0.776, r2 
change = 0.023, p ≤ 0.001).
4 | DISCUSSION
4.1 | Major findings
This study reports significant improvements in car-
diovascular and cerebrovascular indices at the GET and 
VO2max after a 6- month aerobic exercise intervention 
in older sedentary adults from the Brain in Motion study. 
Further, we report evidence of increased functional car-
diovascular and cerebrovascular capacity at submaximal 
exercise workloads. The novelty of this study lies in the 
investigation of the changes in cerebrovascular indices 
during submaximal exercise at workloads that mimic the 
demands of activities of daily function. Previous studies 
have shown favorable cardiorespiratory adaptations and 
increased time to fatigue in older individuals after aerobic 
exercise training (Govindasamy et al., 1992; Poulin et al., 
1992). Our study provides additional evidence showing fa-
vorable effects of aerobic exercise training to the brain in 
older adults.
We report improvements in cerebrovascular indices 
during absolute (65 W) submaximal exercise. Specifically, 
TABLE 3 Pre- and post- intervention cerebrovascular data at rest, relative submaximal exercise (40% of VO2max), and absolute 
submaximal exercise (65 W) for all participants
Variables
Rest
40% VO2max
Rest 2
65 W
Recovery
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Pre- intervention
HR, bpm
64.7
9.2
93.1†
11.8
69.1
10.4
104.9†,#
16.4
75.4
11.9
MAP, mmHg
97.9
11.8
113.8†
15.2
102.5
12.3
121.4†,#
20.0
101.7
13.1
MCAv, cm/s
51.3
11.2
55.7†
12.4
49.7
10.8
54.2†,#
12.5
48.9
10.6
CVRi, mmHg/cm/s
2.01
0.53
2.15†
0.58
2.17
0.60
2.37†,#
0.73
2.1
0.61
CVCi, cm/s/mmHg
0.53
0.14
0.50†
0.14
0.49
0.13
0.46†,#
0.13
0.48
0.13
PETCO2, mmHg
34.3
3.2
36.8†
3.2
33.4
4.0
35.5†,#
4.4
32.7
3.6
PETO2, mmHg
90.3
4.3
89.6†
3.8
94.6
5.0
92.1†,#
5.8
96.5
4.7
Post- intervention
HR, bpm
61.5***
8.8
90.8†,***
10.7
65.6***
9.7
100.3†,#,***
15.1
71.1***
11.2
MAP, mmHg
97.7
11.7
113.2†
15.6
102.2
12.6
117.6†,#,***
18.8
101.4
14.0
MCAv, cm/s
52.7**
11.7
56.8†,*
12.0
50.9*
11.0
55.4†,#,*
11.9
49.8
10.9
CVRi, mmHg/cm/s
1.94**
0.50
2.0†,*
0.54
2.1**
0.52
2.22†,#,***
0.62
2.14
0.59
CVCi, cm/s/mmHg
0.54
0.14
0.51*,†
0.13
0.50
0.14
0.48†,#,***
0.14
0.50*
0.14
PETCO2, mmHg
33.8*
3.0
36.3†,**
3.3
33.0
3.5
35.4#,†
3.7
32.2
3.6
PETO2, mmHg
90.1
4.3
89.4†
4.4
94.4
4.7
91.3†,#,**
5.4
96.0
5.2
Note: Values are means ± standard deviation (SD); Rest and Rest 2 were significantly different for each outcome, both pre-  and post- intervention (all 
p < 0.001).
Abbreviations: bpm, beats per minute; CVCi, cerebrovascular conductance index; CVRi, cerebrovascular resistance index; HR, heart rate; MAP, mean arterial 
pressure; MCAv, velocity at the middle cerebral artery; mmHg, millimeters of mercury; PETCO2, end- tidal partial pressure of carbon dioxide; PETO2, end- tidal 
partial pressure of oxygen.
Significant differences found between pre-  and post- intervention are represented by asterisk (*p < 0.05, **p < 0.005, ***p < 0.001); † indicates significant 
differences from Rest 1 to 40% VO2max and Rest 2 to 65 W; # indicates differences from 40% VO2max to 65 W.
8 of 14 |   
LAKE et al.
we observed significant decreases post- intervention of 3.2% 
in MAP and 6.3% in CVRi, and a 6.1% increase in CVCi. 
Perhaps not surprisingly, the changes in the cardiovascu-
lar and cerebrovascular outcomes during submaximal ex-
ercise at the relative workload (40% VO2max) were more 
modest despite an 8.2% increase in workload (51.0 ± 16.3 
to 55.2 ± 16.9 W from pre-  to post- intervention). These 
findings provide evidence supporting the importance of 
aerobic exercise to confer increases in cardiorespiratory 
fitness, and in turn, improvements in functional capacity 
as manifested by improved indices of brain health in older 
adults.
In this study, two different intensities of submaxi-
mal exercises were selected to evaluate cerebrovascular 
functional capacity at exercise intensities that are compa-
rable to activities of daily function. First, selecting exer-
cise intensities below the GET ensured that exercise was 
performed in the low/moderate- intensity exercise domain 
(Jamnick et al., 2020) when there is no respiratory com-
pensation and PaCO2 and PETCO2 are stable (thus mini-
mizing the possibility of potential confounding factors on 
our measures of MCAv). Second, 65 W represents a VO2 
of approximately 15– 17 ml/kg/min, which has previously 
been referred to as a critical threshold for independent liv-
ing (Paterson et al., 1999). Finally, a relative workload of 
40% VO2max provided a window through which to eval-
uate the gains in functional capacity with improved car-
diorespiratory fitness post- intervention. This conceptual 
framework is depicted in Figure 3, which illustrates the 
relationship between heart rate (bpm) and oxygen uptake 
(VO2, ml/kg/min) during submaximal exercise (65  W) 
before (pre- intervention) and after (post- intervention) 
6 months of aerobic exercise training. Note that the post- 
intervention heart rate is lower at 65 W and at the GET, 
despite a 5% higher VO2 at the GET. Moreover, the change 
in heart rate between submaximal exercise and the GET 
post- intervention is greater than at pre- intervention indi-
cating improved cardiorespiratory fitness (HR ∆1 = 15.1 
vs. ∆2 HR = 18.2 bpm).
A number of studies have described a biphasic asso-
ciation between changes in blood flow to the brain and 
exercise intensity, characterized by parallel increases in 
CBF and exercise intensity until ~60% VO2max. After 
this intensity, and when individuals are closer to the 
GET, the CBF response tends to plateau or even decrease 
if the exercise intensity increases to the point of hyper-
ventilation induced hypocapnia (Ogoh & Ainslie, 2009; 
Smith & Ainslie, 2017). In our data, when considering 
the interplay between some of the main determinants 
of CBF (i.e., MAP and PETCO2) at different exercise in-
tensities, important observations should be made (see 
Table 3). First, when observing the change in PETCO2 
from rest to 40% VO2 and then 65  W, we notice that 
PETCO2 significantly increases by 7.2% from rest to 40% 
VO2, but then significantly decreases by 3.6% from 40% 
VO2 to 65 W. This effect is maintained post- intervention, 
however somewhat attenuated (3.6% decrease in 
PETCO2 from 40% VO2 to 65 W pre- intervention vs. % 
2.7 decrease post- intervention). This suggests a greater 
cardiorespiratory fitness post- training when performing 
exercise at the same intensity (i.e., 65 W). The increase 
in cardiorespiratory fitness is also confirmed by the 
blunted increase in HR post- intervention when exercis-
ing at higher intensities (+12.5% at pre- intervention vs. 
+10.3%). Concomitantly, we observe that MCAv follows 
the same biphasic response with an initial increase at 
40% VO2max (+8%), then a decrease (−2.8%) at a greater 
TABLE 4 Effect sizes and changes (delta pre- /post- 
intervention) in cerebrovascular data at rest, relative submaximal 
exercise (40% of VO2max), and absolute submaximal exercise 
(65 W) for all participants
Variables
Cohens Dz
Delta
Rest
HR, bpm
0.34
−3.12
MAP, mmHg
0.02
−0.36
MCAV, cm/s
0.11
1.37
CVRi, mmHg/cm/s
0.14
−0.07
CVCi, cm/s/mmHg
0.13
0.02
PETCO2, mmHg
0.13
−0.41
PETO2, mmHg
0.06
−0.25
40% of VO2max
HR, bpm
0.20
−2.30
MAP, mmHg
0.03
−0.59
MCAV, cm/s
0.08
1.03
CVRi, mmHg/cm/s
0.10
−0.06
CVCi, cm/s/mmHg
0.07
0.01
PETCO2, mmHg
0.12
−0.46
PETO2, mmHg
0.04
−0.27
65 W
HR, bpm
0.29
−4.60
MAP, mmHg
0.19
−3.62
MCAV, cm/s
0.08
1.02
CVRi, mmHg/cm/s
0.19
−0.13
CVCi, cm/s/mmHg
0.14
0.02
PETCO2, mmHg
0.02
−0.12
PETO2, mmHg
0.14
−0.80
Note: Values are means ± standard deviation (SD).
Abbreviations: bpm, beats per minute; CVCi, cerebrovascular conductance 
index; CVRi, cerebrovascular resistance index; HR, heart rate; MAP, mean 
arterial pressure; MCAV, velocity at the middle cerebral artery; mmHg, 
millimeters of mercury; PETCO2, end- tidal partial pressure of carbon 
dioxide; PETO2, end- tidal partial pressure of oxygen.
   | 9 of 14
LAKE et al.
exercise intensity (65 W), and the same effect persists 
after training. Conversely, when observing the changes 
in MAP with increased exercise intensity, MAP signifi-
cantly increases by 16.2% from rest to 40% VO2max, and 
by a further 6.6% at 65 W. However, while this effect is 
maintained post- intervention it is significantly blunted 
(6.6% increase in MAP from 40% VO2 to 65  W pre- 
intervention vs. 3.9% post- intervention). In turn, CVCi 
linearly decreases (from rest to 40% VO2 to 65 W) in re-
sponse to increases in MAP, and this effect is reduced 
after the intervention, a further indicator of improved 
cardiovascular function after 6 months of aerobic exer-
cise training in older adults.
Previous findings of the effects of aging on cardiovas-
cular outcomes show a 16% decrease in MCAv within 
three decades of life (40– 70 years) which is about 0.53% 
per year (Vriens et al., 1989). Thus, when comparing 
previously published normative data with our results, 
the gains that we observe at post- intervention appear 
to represent an improvement of approximately 5 years 
in brain health— in other words, the MCAv observed 
post- intervention represents an average MCAv observed 
in individuals 5 years younger. The reduction in MAP 
also showed similar gains. It is known that MAP in 
older adults is generally higher at both rest and during 
exercise (Heath et al., 1981). The reduction in MAP ob-
served post- exercise at 65 W further confirms the ben-
eficial effects of exercise for older adults. Altogether, 
the exercise- induced gains attenuate, and may perhaps 
reverse, age- related functional declines in CBF and fos-
ter healthy brain function (Williams & Leggett, 1989). 
This may then translate to a greater capacity to per-
form activities of daily life (Shephard, 2009) such as 
walking independently, shopping, house cleaning, and 
other activities that involve a VO2 of ~15– 17 ml/kg/min 
(Paterson et al., 1999).
In a recent review, Stillman et al. (2020) describe the 
effects of exercise on brain health as mediated by multiple 
mechanisms operating at different system levels. Cellular 
and molecular effects have been primarily studied in 
FIGURE 1 Percent (%) changes from pre-  to post- intervention in cardiovascular and cerebrovascular health outcomes during (a) 
relative (40% VO2max) submaximal exercise and (b) absolute (65 W) submaximal exercise
FIGURE 2 
Heart rate (HR) at 
relative (40% VO2max) submaximal, 
absolute (65 W) submaximal, and 
maximal (VO2max) aerobic exercise pre- 
and post- intervention (I = intervention)
10 of 14 |   
LAKE et al.
animal models. These studies have shown that exercise 
increases brain- derived neurotrophic factor that in turn 
mediates long term potentiation and neuronal prolifera-
tion, vascular endothelial growth factor which supports 
blood vessels, and insulin- like growth factor (IGF)- 1, 
which influences several neural and angiogenic processes 
(Maass et al., 2016; Voss et al., 2013). From a brain struc-
ture perspective (Davenport et al., 2012; Tyndall et al., 
2018), exercise has been shown to promote neurogenesis 
and increase gray matter volume in particular areas of 
the brain (e.g., the hippocampus) linked to memory and 
learning (Erickson et al., 2011), increase cortical thickness 
and volume in the frontal, parietal and temporal cortex 
(Batouli & Saba, 2017), and increased white matter micro-
structure (Clark et al., 2019). Improvements in functional 
connectivity have been also associated with better cogni-
tive function after exercise (Stillman et al., 2016). In this 
paper, we examine the contribution of exercise training to 
the ability of the brain to regulate blood flow to ensure 
adequate delivery of nutrients and oxygen to the different 
brain areas. Specifically, we found that exercise training 
increased blood flow velocity and impacted the ability of 
the brain vasculature to change (increased conductance, 
decreased resistance) in response to an external stimulus 
consisting of bouts of submaximal exercise before and 
after a 6- month aerobic exercise intervention.
Any age- related impairments of cardiovascular 
function, and consequently CBF regulation, may neg-
atively impact the brain's ability to perform cognitive 
tasks (Barnes & Corkery, 2018; Tarumi & Zhang, 2018). 
In a recent study from our laboratory (Guadagni et al., 
2020), we found improved cerebrovascular function at 
rest and improved cognition after the 6- month aerobic 
exercise intervention. We also found novel associations 
between changes in the ability of the cerebral vascula-
ture to react to stimuli (i.e., euoxic hypercapnia) and 
changes in the cognitive domains of executive functions 
and verbal fluency confirming the role of exercise to 
maintain brain health. However, the uniqueness of the 
current study stems from the findings of improvements, 
after 6  months of aerobic training, in cardiovascular 
indices at rest in addition to cerebrovascular function 
during submaximal exercise at workloads that have 
been shown to be comparable to activities of daily func-
tion (Paterson et al., 1999). Previous studies in similar 
populations have identified the importance of physical 
activity in mitigating age- related declines, including 
sarcopenia and cognitive function (Smith & Ainslie, 
2017; Tarumi & Zhang, 2018; Yoo et al., 2018). To our 
knowledge, this study is the first to provide evidence of 
improvements in cerebrovascular function during sub-
maximal exercise shown to be comparable to workloads 
FIGURE 3 Relationship between heart rate (bpm) and oxygen uptake (VO2, ml/kg/min) during submaximal exercise (65 W) before 
(pre- intervention, •) and after (post- intervention, ♦) 6 months of aerobic exercise training. Vertical dash lines represent values before (black) 
and after (grey) 6 months. The dotted lines follow the VO2 values at 65 W, at gas exchange threshold (GET) and VO2max before (black) and 
after (grey) 6 months. Delta 1 (∆1) represents changes in submaximal heart rate pre-  to post- intervention (HR∆1 = 4.6 bpm). Delta 2 (∆2) 
represents changes in HR between 65 W and VT1 pre- intervention (HR∆2 = 15.1 bpm). Delta 3 (∆3) represents changes in HR between 65 W 
and VT1 post- intervention (HR∆3 = 18.2 bpm)
   | 11 of 14
LAKE et al.
that are required in activities of daily living in a large 
sample of middle- aged and older adults after an exten-
sive period of training.
4.2 | Limitations
The present study has some limitations, which warrant a 
short discussion. First, the lack of a control group in the 
study precludes the ability to make firm conclusions on 
the exclusive role of the aerobic exercise intervention in 
improving cardiovascular and cerebrovascular indices. 
However, we have previously published data on lack of 
changes in cerebrovascular outcomes in the 6  months 
preceding the intervention (Spencer et al., 2015). These 
previous findings strengthened the role of the interven-
tion in the improvements observed in this report. Second, 
this cohort was composed of healthy, well- educated, 
mostly Caucasian men and women. As such, our re-
sults cannot be generalized to other populations nor to 
patients with symptom- limited exercise capacity. Third, 
the two different submaximal workloads were not rand-
omized, and this may have impacted results and should 
be addressed in future studies. Fourth, the use of TCD 
assumes that the cross- sectional area of the blood ves-
sel being insonated (i.e., the MCA) remains unchanged 
(Poulin et al., 1996). Moreover, we only measured unilat-
eral (right) MCA while assessment of other large blood 
vessels and/or global CBF may have yielded different 
results (Al- Khazraji et al., 2019). Fifth, the use of finger 
pulse photoplethysmography to make continuous meas-
ures of blood pressure has intrinsic limitations (Maestri 
et al., 2005), which we have compensated for with the 
use of a correction factor based on brachial measure-
ments. Sixth, participants were asked to complete an ad-
ditional unsupervised exercise session once a week and 
record these and other workouts done on their own in a 
logbook. These additional sessions were not accounted 
for in our analyses. Finally, we did not collect any vali-
dated direct measure of activities of daily living (ADLs). 
We however used the Profile of Mood States (POMS) 
questionnaire to evaluate changes in participants’ mood 
and vigor from pre-  to post- intervention. We found sta-
tistically significant decreases (all p  <  0.05, data not 
shown) post- intervention in the subscales of Confusion 
(pre- intervention 6.3 ± 2.8, post- intervention 5.9 ± 2.6), 
Tension (pre- intervention 7.9  ±  3.6, post- intervention 
7.3 ± 3.5), and Total Mood Disturbance (pre- intervention 
11.5 ± 20.6, post- intervention 7.9 ± 20.2) and a signifi-
cant increase (p < 0.001, data not shown) in Vigor (pre- 
intervention 18.8  ±  5.4, post- intervention 19.8  ±  5.1). 
These changes may be used as surrogate measures for 
improvements in daily life.
4.3 | Significance and conclusions
Previous reports on the functional ability of older popula-
tions have shown progressive declines in aerobic exercise 
capacity with age, which is associated with reductions in 
physical functional capacity, and decreases in independ-
ence and quality of life (Christou & Seals, 2008; Huggett 
et al., 2005; Robinson, 1938). Age- related declines in cog-
nitive abilities, characterized by chronic and progressive 
conditions such as dementia, can also reduce the ability 
to independently perform activities of daily living (Public 
Health Agency of Canada, 2019). Addressing physical in-
activity, an established risk factor of dementia (Livingston 
et al., 2020), and implementing appropriate exercise inter-
ventions, individuals hold promise for reducing the eco-
nomic and functional burden of dementia.
In conclusion, studies aiming to advance knowledge 
of the mechanisms underlying the decline in cardiovas-
cular and cerebrovascular capacity with aging have im-
portant implications for older adults. Our study suggests 
that aerobic exercise might improve cardiovascular and 
cerebrovascular indexes at submaximal exercise levels 
which are comparable to daily life activities. Future stud-
ies are needed to confirm these findings and extend them 
to other populations and to specific activities of daily 
living.
ACKNOWLEDGMENTS
We would like to thank all participants of the Brain in 
Motion study and the Brain in Motion study team.
CONFLICT OF INTEREST
All authors report no conflict of interest.
AUTHOR CONTRIBUTIONS
Sonja L. Lake and Veronica Guadagni share co- first 
authorship and equally contributed to the manuscript. 
Marc J. Poulin, David B. Hogan, Michael D. Hill, and 
Todd J. Anderson designed the study; Karen D. Kendall 
and Michaela Chadder conducted the maximal oxygen 
uptake (VO2max) tests and analysed the data for deter-
mination of GET and RCP; David B. Hogan, Michael 
D. Hill, Todd J. Anderson, Richard Leigh, and Jean M. 
Rawling completed medical assessments and provided 
medical coverage for the VO2max tests; Sonja L. Lake 
and Veronica Guadagni organized the data and con-
ducted the data analyses. All authors interpreted the 
data. Sonja L. Lake and Veronica Guadagni drafted the 
manuscript. All authors read, edited and approved the 
final draft of the manuscript.
ORCID
Marc J. Poulin 
 https://orcid.org/0000-0002-1798-6801 
12 of 14 |   
LAKE et al.
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How to cite this article: Lake, S. L., Guadagni, V., 
Kendall, K. D., Chadder, M., Anderson, T. J., Leigh, 
R., Rawling, J. M., Hogan, D. B., Hill, M. D., & 
Poulin, M. J. (2022). Aerobic exercise training in 
older men and women— Cerebrovascular responses 
to submaximal exercise: Results from the Brain in 
Motion study. Physiological Reports, 10, e15158. 
https://doi.org/10.14814/ phy2.15158

Aerobic exercise training in older men and women-Cerebrovascular responses to submaximal exercise: Results from the Brain in Motion study.
Lake, Sonja L,Guadagni, Veronica,Kendall, Karen D,Chadder, Michaela,Anderson, Todd J,Leigh, Richard,Rawling, Jean M,Hogan, David B,Hill, Michael D,Poulin, Marc J