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. Author manuscript; available in PMC: 2022 Nov 1.
Published in final edited form as: Nephrol Nurs J. 2021 Nov-Dec;48(6):553–561.

The Influence of Sedentary Behavior on the Relationship Between Cognitive Function and Vascular Function in Older Adults with and without Chronic Kidney Disease

Mary Hannan 1, Eileen G Collins 2, Shane A Phillips 3, Lauretta Quinn 4, Alana Steffen 5, Ulf G Bronas 6
PMCID: PMC9113049  NIHMSID: NIHMS1796638  PMID: 34935333

Abstract

Cognitive impairment and vascular dysfunction are common in older adults with and without chronic kidney disease (CKD). Older adults with and without CKD are also sedentary – a behavior associated with cognitive and vascular function. The objective of this study was to explore whether sedentary behavior influenced the relationship between cognitive and vascular function in older adults with preclinical cognitive impairment with and without CKD. In our study, 48 older adults underwent assessment of cognition, vascular compliance, and sedentary behavior, and relationships were explored with regression moderation analysis. Sedentary time and breaks did not moderate the relationship between vascular and cognitive function. Although significant moderation was not found, cognition, vascular function, and sedentary behavior are important to assess when evaluating older adults with and without CKD.

Keywords: Chronic kidney disease, CKD, older adults, gerontology, preclinical cognitive impairment, cognitive function, vascular function, sedentary behavior

Sedentary behavior is common in older adults, with findings from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 cohort revealing that those over the age of 60 years spend greater than 9 hours per day being sedentary (Healy, Clark et al., 2011). Sedentary behavior is especially common in older adults with chronic kidney disease (CKD), who spend the majority of their waking hours sedentary (Beddhu et al., 2015; Parsons et al., 2017; Robinson-Cohen et al., 2013; West et al., 2017). This is concerning because sedentary behavior has been implicated in numerous adverse health outcomes (de Groot et al., 2006; Hamilton et al., 2007; Owen et al., 2010; Thosar et al., 2012; Younan, 2018), with the U.S. Department of Health and Human Services (HHS) Physical Activity Guidelines (2nd edition) even recommending that individuals “move more and sit less” (HHS, 2018; Piercy et al., 2018).

Cognitive impairment is associated with sedentary behavior (Aichberger et al., 2010; Falck et al., 2017; Lipnicki & Gunga, 2009). Sedentary behavior also influences blood vessel function and structure, and vascular dysfunction, particularly arterial stiffness, has been associated with worse cognitive performance (Benetos et al., 2012; Hamilton et al., 2007; Muela et al., 2017; Pase et al., 2012; Rabkin, 2012; Scuteri et al., 2005; Thosar et al., 2012; Waldstein et al., 2008; Zeki Al Hazzouri & Yaffe, 2014). Vascular dysfunction is an outcome of prolonged sedentary behavior and associated with cognitive impairment, which suggests that vascular dysfunction could possibly be the unifying theory behind the relationship between sedentary behavior and cognitive function. Determining this relationship and factors that influence this relationship is critically important for older adults, particularly for those with CKD, since cognitive impairment and vascular dysfunction are extremely common in individuals with CKD (Mizobuchi, 2009; Murray et al., 2006; Tamura et al., 2016). There are limited evidence-supported therapies to prevent the cognitive decline associated with aging and the cognitive impairment noted in individuals with CKD (Bronas et al., 2017; Dumas, 2017). Having high levels of physical activity is associated with better cognition in the general population (Sofi et al., 2011), but older adults and those with CKD report great barriers to exercise participation (Hannan & Bronas, 2017; Schutzer & Graves, 2004). It is therefore essential to explore other interventions, such as ways to “move more and sit less” (HHS, 2018; Piercy et al., 2018), for older adults with and without CKD that have the potential to improve cognition. One of the first exploratory steps in this line of inquiry is to assess the influence of sedentary behavior on the relationship between vascular dysfunction and cognitive impairment.

The purpose of this study was to explore whether sedentary behavior influences the relationship between cognitive function and vascular function (see Figure 1) in older adults with preclinical cognitive impairment with and without CKD. It is hypothesized that lower levels of sedentary time and increased number of sedentary breaks will moderate the relationship between vascular function and cognitive function in older adults with and without CKD.

Figure 1.

Figure 1

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Hypothesized Relationship – Cognitive Function, Vascular Function, and Sedentary Behavior

Methods

Study Population

As previously described in detail (Hannan et al., 2020), the population of interest for the study was community dwelling adults aged 60 to 80 years with preclinical cognitive impairment, defined as self-identified cognitive decline (Jessen et al., 2014), with and without CKD (estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2 by the CKD-EPI equation) who met inclusion criteria. Informed consent was obtained from all participants. The study was approved by the University of Illinois Chicago Institutional Review Board (IRB).

Measures

As described previously (Hannan et al., 2020), cognitive function was measured with the Montreal Cognitive Assessment (MoCA), a brief screening test that evaluates global cognitive function (Nasreddine et al., 2005). Vascular function was assessed via arterial stiffness: regionally, with carotid-femoral pulse wave velocity (cfPWV), and locally, with ultrasound evaluation of carotid compliance and endothelial function, which was measured via brachial artery flow mediated dilation (FMD), following standard protocols (Anderson & Phillips, 2014; Townsend et al., 2015).

As described previously (Hannan et al., 2021), sedentary behavior was assessed with actigraphy (ActiGraph, GTX3) (Byrom & Rowe, 2016; Troiano et al., 2008). Participants were instructed to wear the ActiGraph for one week, with removal only for bathing or showering (Agarwal & Light, 2011; Byrom & Rowe, 2016; Tentori et al., 2010). Non-wear time and time spent sleeping were removed from the analysis. Sedentary time and sedentary breaks (a non-sedentary period following being sedentary) (Tremblay et al., 2017) were evaluated based on criteria established by previous work utilizing ActiLife software (ActiGraph) (Bann et al., 2015; Byrom & Rowe, 2016; Chastin & Granat, 2009; Freedson et al., 1998; Healy, Matthews et al., 2011; Jefferis et al., 2015; Pate et al., 2008; Tudor-Locke et al., 2012).

Statistical Analysis

All statistical analyses were conducted with Stata Statistics/Data Analysis (Version 14.2). Data were not included in the analysis if a measure was unable to be obtained (see Tables 1 and 2). The moderating influence of sedentary behavior on the relationship between vascular function and cognitive function was evaluated in this exploratory study utilizing ordinary least squares (OLS) regression moderation analysis. Cognitive function (total MoCA score) was regressed on each vascular index, and the moderating influence of sedentary time and sedentary breaks were explored in separate regressions and included relevant covariates (age, level of education, and history of smoking).

Table 1.

Sample Characteristics

Characteristic Whole Sample Mean (SD/%)
n = 48		 Non-CKD Mean (SD/%)
n = 24		 CKD Mean (SD/%)
n = 24
Demographics
Age 68.5 (5.5) 68.5 (5.5) 68.4 (5.6)
Sex
 Male (%) 26 (54.2) 14 (58.3) 12 (50)
 Female (%) 22 (45.8) 10 (41.7) 12 (50)
Education Years 15.2 (2.1) 16.6 (1.4) 13.75 (1.6)
Race
 African American (%) 18 (37.5) 2 (8.3) 16 (66.7)
 Asian (%) 1 (2.1) 0 1 (4.2)
 Caucasian (%) 27 (56.2) 22 (91.7) 5 (20.8)
 Chose not to report (%) 2 (4.2) 0 2 (8.3)
Medical Factors
eGFR 63.3 (22.9) 82.7 (12.3) 43.9 (11.6)
Current smoking (%) 9 (18.8) 2 (8.3) 7 (29.1)
History of smoking (%) 24 (50) 10 (41.7) 14 (58.3)
Antihypertensive (%) 29 (60.4) 7 (29.2) 22 (92)
Cognitive Function
Total MoCA Score 24.92 (3.36) 26.79 (2.69) 23.04 (2.93)
Vascular Function
cfPWVa (m/s) 8.06 (1.47) 7.45 (0.96) 8.66 (1.65)
cIMT (mm) 0.82 (0.13) 0.84 (0.11) 0.79 (0.14)
Distensibility coefficient (10–3/mmHg) 0.002 (0.001) 0.003 (0.001) 0.002 (0.001)
Young’s modulus (mmHg/cm) 1087.7 (457.0) 888.8 (324.3) 1286.6 (489.0)
Elastic modulus (mmHg/cm) 15500.5 (6353.1) 13017.5 (4059.1) 17983.5 (7289.4)
Stiffness index (mmHg/cm) 0.006 (0.004) 0.005 (0.003) 0.006 (0.006)
FMD (%) 5.48 (2.97) 4.63 (1.97) 5.90 (2.95)
Sedentary Behavior
Sedentary Time per Day (minutes) 673.2 (118.8) 654.2 (106.3) 692.2(129.5)
Sedentary Breaks Per Day 18.0 (4.2) 18.2 (3.5) 17.8 (4.8)
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a

cfPWV n = 46 for the total sample, n = 23 for the non-CKD group, and n = 23 for the CKD group (unable to obtain measure).

Table 2.

Moderation Analysis

Regression Moderation Analysis- Global Cognitive Function (total MoCA score)b (independent variable -interaction term) R 2 p R2 with Interaction p Increase in R2 t of Interaction Term p of Interaction Term
cfPWV – Sedentary Timea 0.33 0.01 0.33 0.01 0.001 −0.19 0.85
cfPWV – Sedentary Breaka 0.33 0.01 0.34 0.01 0.004 0.47 0.64
cIMT – Sedentary Time 0.25 0.03 0.26 0.05 0.009 −0.72 0.48
cIMT – Sedentary Break 0.25 0.02 0.25 0.05 0.002 −0.35 0.73
Distensibility Coefficient – Sedentary Time 0.24 0.03 0.26 0.05 0.012 0.82 0.42
Distensibility Coefficient – Sedentary Break 0.25 0.03 0.27 0.04 0.023 1.12 0.27
Youngs – Sedentary Time 0.25 0.03 0.25 0.05 0.010 −0.75 0.46
Youngs – Sedentary Break 0.25 0.03 0.28 0.03 0.031 −1.32 0.19
Elastic Modulus – Sedentary Time 0.26 0.03 0.28 0.03 0.021 −1.09 0.28
Elastic Modulus – Sedentary Break 0.26 0.02 0.30 0.02 0.042 −1.57 0.13
Stiffness Index – Sedentary Time 0.24 0.03 0.25 0.06 0.005 −0.52 0.61
Stiffness Index – Sedentary Break 0.24 0.03 0.24 0.06 0.001 0.17 0.87
FMD – Sedentary Time 0.24 0.04 0.30 0.02 0.062 −1.91 0.06
FMD – Sedentary Break 0.24 0.04 0.27 0.04 0.026 −1.21 0.23
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a

cfPWV n = 46 for the total sample, n = 23 for the non-CKD group, and n = 23 for the CKD group (unable to obtain measure).

b

Covariates age, years of education, and history of smoking.

Results

The sample was over half male (54.2%) with a mean age of 68.5 (5.5) years. The mean level of education was 15.2 (2.1) years, and 50% had a history of smoking. The mean total MoCA score of the entire sample was 24.9 (3.4), with those with CKD having a lower score compared to those without CKD (23.04 versus 26.79). The mean cfPWV for the entire sample was 8.06 (1.47)m/s, mean cIMT was 0.82 (0.13) mm, mean distensibility coefficient was 0.002 (0.001) 10−3/mmHg, mean Young’s modulus was 1087.7 (457.0) mmHg/cm, mean elastic modulus was 15500.5 (6353.1)mmHg/cm, mean stiffness index was 0.006 (0.004) mmHg/cm, and mean FMD was 5.48 (2.97)%. The mean total sedentary time for the entire sample was 673.2 (118.8) minutes per day and the mean number of sedentary breaks per day for the entire sample was 18 (4.2), and those with CKD had higher sedentary time and fewer sedentary breaks per day than those without CKD (see Table 1).

In the regression moderation analysis, the largest increase in the amount of the variance explained (R2) in the relationship between cognitive and vascular function was the moderating influence of sedentary time on the relationship between the MoCA score and FMD (R2 increase of 0.06), and the moderating influence of sedentary breaks on the relationship between the MoCA score and the elastic modulus (R2 increase of 0.04). None of the interaction terms were significant (p < 0.05) in the moderation analyses (see Table 2).

As an additional exploration, moderation analysis was conducted separately for those with and without CKD. For those without CKD, sedentary time moderated the relationship between cfPWV and MoCA with an increase in the variance explained in the relationship (R2 increase of 0.15 [interaction term t = 2.25, p = 0.04]). The moderating influence of sedentary behavior on the relationship between vascular function, and cognitive function was not found when looking only at older adults with CKD.

Discussion

This exploratory study uniquely investigated the influence of sedentary behavior on the relationship between vascular function and cognitive function in older adults with preclinical cognitive impairment with and without CKD. Sedentary time and breaks did not moderate the relationship between the indicators of vascular function and the score on the cognitive function test. The interactions were not significant, potentially due the exploratory nature of this study and the small sample size, so more investigation into this relationship is needed.

Sedentary behavior is associated with adverse health outcomes that are distinct from consequences associated with insufficient exercise (Owen et al., 2010). Although beyond the scope of this study, there are unique physiological changes and metabolic consequences that occur with prolonged sedentary time, including suppression or expression of specific genes, molecular responses, lipid dysregulation, and altered lipoprotein lipase activity (Hamilton et al., 2007; Owen et al., 2010). This study sought to examine the role that sedentary behavior may play in two interrelated complications of aging and CKD – vascular dysfunction and cognitive impairment. We hypothesized that these three factors have a unique relationship, since vascular dysfunction is associated with worse cognitive performance, sedentary behavior can cause vascular changes, and sedentary behavior has been associated with cognitive impairment (Aichberger et al., 2010; Benetos et al., 2012; de Groot et al., 2006; Falck et al., 2017; Lipnicki & Gunga, 2009; Muela et al., 2017; Pase et al., 2012; Rabkin, 2012; Scuteri et al., 2005; Shvartz et al., 1983; Thosar et al., 2012; Waldstein et al., 2008; Williamson et al., 2009; Zeki Al Hazzouri & Yaffe, 2014). Although sedentary time is associated with white matter hyperintensity volume in individuals with eGFR less than or equal to 96 mL/min/1.73m2, with the association being stronger with lower levels of kidney function (Bronas et al., 2019), the moderating role of sedentary time has not been previously explored in the relationship between cognition and vascular function, particularly for those with CKD.

In our exploratory study, there are possible reasons why sedentary time did not exert a moderating influence on the relationship between vascular and cognitive function. It may be narrow-focused to attribute changes in cognition due to vascular function and sedentary time alone, since brain health is influenced by a multitude of physiological, genetic, social, and environmental factors (Gregory et al., 2012). It is unclear the extent that each of these factors influence brain health and if one or numerous factors supersede others. It is also unclear when cognitive impairment and vascular dysfunction are most amenable to change and what degree and type of change in sedentary behavior may be necessary to exert a positive influence (Kramer et al., 2008). It is also possible that a moderating influence was not found in our study because it is not clear exactly how much sedentary time causes harm (Thosar et al., 2012), and conversely, how low does sedentary time need to be to exert beneficial effects on the vasculature, and subsequently, cognitive function. More work is needed to determine if there is a tolerable amount of sedentary time that exerts minimal harm and has the potential to moderate the relationship between vascular function and cognition in older adults with and without CKD.

Interestingly, when looking separately at those with and without CKD, sedentary time exerted a moderating influence on the relationship between regional aortic stiffness (cfPWV) and global cognition (total MoCA score) only in those without CKD. It is possible this relationship was unique to those without CKD because of the distinct characteristics of the vascular dysfunction of CKD. Individuals with CKD can have vascular calcification that leads to thickening of the elastic layer of arteries, deposition of increased extracellular matrix, destruction of the elastic components, inflammation, increased collagen content, and narrowing of the vascular lumen (Georgianos et al., 2015; Goodman et al., 2004; Mizobuchi, 2009). Conversely, with aging, there is stiffening of the aorta while the muscular arteries do not stiffen (Mitchell, 2008). The lack of moderation may also be related to the unique type of cognitive impairment found in individuals with CKD. Individuals with CKD commonly have executive function domain deficits (Kurella et al., 2004; Kurella, Yaffe et al., 2005; Puy et al., 2018; Slinin et al., 2008; Weiner et al., 2017; Yaffe et al., 2010), whereas the cognitive impairment of aging is typically nonspecific cognitive slowing, particularly in new situations (Lindeboom & Weinstein, 2004). There is a need for more investigation into the influence of sedentary time on the relationship between vascular function and cognitive function in those with CKD.

Implications for Practice

Through this exploratory study, we highlighted the importance of considering cognitive function, vascular function, and sedentary behavior when caring for older adults with preclinical cognitive impairment with and without CKD. Nephrology nurses and their focus on caring for patients’ physiological, psychological, and social health (Bednar & Latham, 2014) make them well suited to evaluate and develop interventions for older adults with CKD with cognitive impairment, vascular dysfunction, and high amounts of sedentary behavior. Nephrology nurses also have a vital role in their scope of practice to educate older adults with CKD and their caregivers about cognitive impairment, vascular dysfunction, and sedentary behavior, and what can be done to potentially address these complications of aging and CKD (Gomez, 2017).

Our study supports that older adults with CKD should have assessment of their cognitive function, vascular function, and sedentary behavior. In our study, older adults with CKD had lower scores on the cognitive function test, higher scores on some indicators of arterial stiffness, and higher sedentary time per day. Cognitive function should be assessed in older adults with CKD given the high prevalence of cognitive impairment in this population (Kurella, Chertow et al., 2005). Since the vasculature has been implicated as having a role in cognitive function in those with CKD (Bronas et al., 2017), it is important for nurses to also assess factors that could potentially increase vascular risk, such as smoking (Kidney Disease: Improving Global Outcomes [KDIGO] CKD Workgroup, 2013). Given the association between sedentary behavior and adverse health outcomes (de Groot et al., 2006; Hamilton et al., 2007; Owen et al., 2010; Thosar et al., 2012; Younan, 2018), it is also important to assess barriers to increasing physical activity that individuals with CKD endorse (Hannan & Bronas, 2017).

Limitations

This study was not without limitations. The study was an exploratory study that was not powered to support significant associations from this analysis, and the sample was a convenience sample. The study is cross-sectional, so it does not support conclusions of causation. Although relevant confounders were added to the regressions, not all potentially relevant confounders that could influence cognition, vascular function, and sedentary time were added due to the small sample size. The two groups –those with and without CKD – were different in regard to racial makeup, education level, and comorbidity, which may have influenced results. Antihypertensives were not held prior to vascular testing due to the comorbidities of the sample, which could have influenced the vascular compliance measures (Van Bortel & Kool, 1994). Despite the limitations, the study had great strength in its novel exploration into the moderating influence of sedentary time on the relationship between vascular function and cognition, which was the first time done per the authors’ knowledge. The study also had great strength in its assessment of vascular function with numerous methods and the utilization of device assessed sedentary behavior.

Conclusion

This study explored the potential influence of sedentary behavior on the relationship between vascular function and cognitive function in older adults with and without CKD. Although significant moderation was not found, our findings support the need for assessment and evaluation of cognitive impairment, vascular function, and sedentary behavior in these at-risk populations.

Acknowledgments

Funding:This study was supported by a grant made available by the American Nephrology Nurses Association (ANNA). Findings of the study do not necessarily reflect the opinions of ANNA. The views expressed herein are those of the author and no official endorsement by ANNA is intended or should be inferred.

The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR002003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Dr. Bronas and the parent study were supported by NIH-NIA AG022849-15S1 and NIH-NIA AG022849.

Dr. Hannan is a T32 Postdoctoral Fellow. Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL134634. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Dr. Hannan is a Robert Wood Johnson Foundation Future of Nursing Scholar Postdoctoral Fellow. The views expressed here do not necessarily reflect the views of the Foundation.

Footnotes

Statement of Disclosure: The remaining authors reported no actual or potential conflict of interest in relation to this nursing continuing professional development (NCPD) activity.

Contributor Information

Mary Hannan, Post-Doctoral Fellow, the University of Illinois Chicago, College of Medicine, Department of Medicine, Chicago, IL; an American Society of Nephrology Kidney Cure Sharon Anderson Research Fellow; and a member of ANNA's Windy City Chapter..

Eileen G. Collins, Dean of the College of Nursing, the University of Illinois Chicago, College of Nursing, Department of Biobehavioral Nursing Science, Chicago, IL..

Shane A. Phillips, Professor and the Senior Associate Dean for Clinical Affairs, the University of Illinois Chicago, College of Applied Health Sciences, Department of Physical Therapy, Chicago, IL..

Lauretta Quinn, Professor, the University of Illinois Chicago, College of Nursing, Department of Biobehavioral Nursing Science, Chicago, IL..

Alana Steffen, Research Assistant Professor, the University of Illinois Chicago, College of Nursing, Department of Population Health Nursing Science, Chicago, IL..

Ulf G. Bronas, Associate Professor, the University of Illinois Chicago, College of Nursing, Department of Biobehavioral Nursing Science, Chicago, IL..

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