Effects of therapeutic exercise on cognition in adults with hypertension: A systematic review

Insha Farooq M.P.T., Sarah Parveen M.P.T., Majumi M. Noohu Ph.D.
Centre for Physiotherapy & Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India

Introduction

The force produced by blood pushing against the walls of the body’s arteries or great vessels is known as blood pressure (BP) [1]. BP is represented as systolic blood pressure (SBP) and diastolic blood pressure (DBP). The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hyper­tension (HTN) guidelines for the prevention, discovery, assess­ment and treatment of high BP in adults define HTN as SBP ≥130 mmHg and DBP ≥80 mmHg, replacing the previous cutoff of 140/90 (SBP/DBP) mmHg as defined by the guidelines of Eighth Joint National Committee (JNC 8) in 2014 [1,2]. The new recommendations were founded on the idea that BP control might preserve vascular health in adolescence and guard against cardiovascular disease (CVD) and organ damage later in life. From this perspective, the new guidelines are of great significance [3]. The recent change in the 2017 guidelines suggests that a low cutoff of 130/80 mmHg appears to be logical for diagnosing and treating patients suffering from HTN [4,5].
Uncontrolled high BP can cause several problems such as heart attack or stroke, aneurysm, congestive heart failure, weakening and thinning of blood vessels in the kidneys, and cognitive impairment [6]. The cognitive function play a fundamental role in day to day life, and this decline can be characterized by memory difficulties [7], deprived mental flexibility, and lesser ability to inhibit responses [8]. In the last 20 years, several studies have found that HTN is a risk factor not only for Alzheimer’s disease (AD) but also for mild cognitive impairment (MCI) [9]. In a 2-year follow-up study of 385 MCI patients, Goldstein et al. [10] showed that cognitive function (such as attention, executive function, and naming) of subjects with hyperten­sion, compared to subjects without hypertension, significantly declined, especially in those with SBP ≥140 mmHg, or DBP ≥90 mmHg.
Regular aerobic exercise can influence cognitive function by increasing brain oxygenation due to a greater blood flow and perfusion, which directly influences cognition, regardless of age [11]. However few studies investigated the use of aerobic exercise as a strategy for reducing cognitive decline in hypertensive patients, and they differ in intensity, duration, and type of exercise used [12]. On the other hand, resistance exercise helps in the up-regulation of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial-derived growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) [13]. These neurotrophic factors are thought to balance the beneficial effects of exercise on brain plasticity and cognitive function [13]. Notably, resistance training is mainly effective for rising levels of serum IGF-1 in older adults [14]. IGF-1 in the periphery can exceed the blood-brain barrier and plays an important role in vascular protection and remodeling [15].
The primary aim of our paper was to conduct a systematic review and quantify the effect of exercise training, that is aerobic and resistance training, on cognitive functions in ­patients with BP.

Methods

This systematic review was conducted according to the ­Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines. The protocol was registered in the International Prospective Register of Systematic ­Review (PROSPERO) under the registration number CRD42021277883.

Eligibility criteria

The participants included in this study were adults diagnosed with HTN and indicators of cognition. No limits were made on gender or disease duration or severity of the disease. The articles included in this review are randomized controlled trials and cohort studies. All the articles were published in English. The studies with adolescents were excluded. Animal studies were also excluded. The evaluation contains trials involving the delivery of rehabilitation therapies to individuals with HTN who are experiencing problems with their cognitive abilities. The comparisons included exercise alone, exercise combined with dietary interventions, any other intervention or care in the control group. The main outcome measure of this study was cognition which includes executive functioning, memory formation, psychomotor speed, and attention. These outcome measures were assessed with the usage of different tools.

Search strategy

A systematic search was done on MEDLINE (accessed by PubMed), Cochrane, ­Scopus, and Web of Science (Web of Science Core Collection) till June 2022, using the following search terms: therapeutic exercise, aerobic exercise, hyper­tension, hypertensive, cognition, and cognitive function. These search terms were combined with Boolean operators in between ‘OR’ and ‘AND’ to broaden or narrow the search strategy. Details of the search strategy is reported in table 1.

Study selection

We included randomized controlled trials (RCTs) and cohort studies showing the effectiveness of exercise on cognition in patients with HTN. We started by manually identifying and removing duplicate references, and then we looked at titles and abstracts for relevance. All articles that matched the inclusion criteria were reviewed in full text.

Data extraction and analysis

Study characteristics were extracted from each study upon study design, inclusion and exclusion criteria, research location, participation information, intervention measure descriptions, control measure descriptions, and outcome measures.

Quality assessment

Quality assessment of RCTs was done with the help of PEDro which is a physiotherapy evidence database in which trials are independently assessed for quality [16] and for cohort study national institute of health (NIH) tool was used [17].

Results

A total of 28 546 records have been identified through the preliminary database search. After duplication removal, 19 514 records were screened, followed by retrieval of ­records. Out of 1140, one hundred and seven records were assessed for full-text review, and at last 6 records were considered relevant and compliant with all the inclusion criteria (Fig. 1).

Study characteristics

The participants included in this study were adults diagnosed with HTN. A detailed summary of characteristics is shown in table 2.

Study design

The trials included in this review were five RCT and one cohort study.

Participants

Six selected studies comprised 2458 participants with a sample size between 21 [20] to 1401 [21] subjects. Most of the participants were more than 50 years of age inclusive of both genders.

Intervention

All the studies investigated the effect of exercise training including aerobic training [18-20], and resistance training [20,21]. In four [19,20,21,22] out of six studies the exercise training lasted for 6 months. The period of each session varied from 5 minutes [23] to 1 hour [22], the frequency was between 2 to 5 times weekly [19,21,22]. In one study, the total period of exercise lasted for 16 weeks with a time duration of 10 to 35 minutes and a frequency of 2 to 3 sessions per week [18]. One study did not provide any information regarding the duration of each session [23]. In one study exercise sessions lasted for 12 weeks, 3 times per week. The volume of both exercise programs (aerobic or resistance training) gradually increased throughout the first weeks, so that the main part of the session lasted 20 min within the first week, 30 min in the second week, and 40 min in the following weeks. The aerobic exercises included were walking, jogging, and stationary biking. One study included high-intensity cycling [22] and one study included bench press and upper and lower extremity resistance exercises for main muscle groups [21], the study has not mentioned the equipment used for resistance exercises for a muscle group (table 3).

Outcome measures

Only one study out of six used Mini-Mental State Examination (MMSE) for assessing cognition [21]. Four studies used the Wechsler Intelligence Scale for assessing the memory of the participants [18,19,22,23]. One study used a Mental Test and Training System (MTTS) at baseline and after the 12-week exercise intervention [20]. In two studies, the global cognitive performance was assessed by verbal fluency, modified Boston naming, trail-making test, and Cambridge Brain Science battery (CBS) [21,22]. One study used the Eriksen Flanker test for memory and executive function [23].

Quality of trials

Quality scoring was performed using the PEDro scale (table 4). One trial scored 7/10 [19], one study scored 8/10 [21], two scored 6/10 [20,22] and one scored 4/10 [18]. Five studies randomly allocated the subjects into groups but only one maintained a concealed allotment [21]. Three of the ­
trials did not blind either of the subjects, therapists, or assessors [18,20,22]. However, in two studies blinding of assessors was done [19,22]. For the quality assessment of the cohort study [23], the NIH tool was used and the response was good (table 5).

Effects of exercise training on cognition

Only one study showed an increase in memory [19]. Two studies showed an increase in executive function after training the subjects with aerobic exercise [19,23]. Two studies showed improved processing speed in hypertensive patients. A study by Blumenthal et al. showed that participants randomized to exercise demonstrated better performance in the executive function domain compared to the non-exercisers from the control group [19]. However, two out of six studies showed no significant difference between groups [18,22]. Two studies showed that aerobic exercise combined with diet improved global cognition [19,21]. Boa et al. observed improvements in both groups in processing speed and mental flexibility [22].

Discussion

To the best of our knowledge, this is the first systematic review providing complete details on the findings, properties, and quality of clinical trials investigating the effect of exercise training on cognition in patients with high blood pressure. So, the effectiveness of exercise to improve cognition in those with HTN remains to be determined, as there is a lack of RCTs on aerobic exercise to improve cognition in adults with hypertension. Only a few studies have shown that aerobic exercise improves cognition in patients with hypertension. Other studies found that aerobic exercise in combination with the DASH diet can improve cognition in patients with hypertension.
A study by Boa et al. [19] has shown positive results, in which 160 patients with HTN having cognitive impairment without dementia (CIND) were recruited and received aerobic exercise training for 6 months (3 months supervised and 3 months unsupervised). The trial showed that the participants demonstrated better executive functioning compared to controls by refining neurocognition, including increased neurotrophic factors related to neurotransmission, improved hippocampal neurogenesis, increased cerebral blood flow and improved brain plasticity. Additionally, better aerobic fitness has been shown to be associated with greater brain volume, which is linked with enhanced cognitive performance, and exercise has been shown to potentially improve cerebral blood flow. A cohort study done by Lefferts et al. [23] on hypertensive and non-hypertensive patients, in which aerobic exercise was given to both groups in the form of moderate intensity cycling for 30 minutes at a 55% VO_2peak, has shown that there is an improvement in processing speed domain of executive function in non-hypertensive as well as hypertensive patients. However, no improvements in the memory were seen.
A 4-month RCT was done by Pierce et al. [18], in which they randomly assigned the subjects into 3 groups: are strength training group, an aerobic exercise group, and a control group. In his study, he discovered that the aerobic capacity of subjects assigned to the aerobic training group increased by 16% over the 4 months training period, whereas increase of 4 and 1% were observed for subjects assigned to the strength training and waiting list groups, respectively. Although the outcome of this study is negative because the subjects were not clinically anxious or depressed, there is a chance that exercise may be connected with improvements in mood in subjects having a more negative effect. Boa et al. [22] recruited 128 community-dwelling older adults who were trained with resistance exercise, that is high intensity interval training for 6 months, did not show any changes in global cognitive function, but there was an increase in the processing speed in both groups. This increase in speed takes place due to the increase in blood flow to the brain and neuroplasticity.
Komulainen et al. found that moderate-intensity aerobic exercise combined with a healthy diet, but no other combinations of lifestyle interventions, showed a drift towards improved global cognition during 4 years in middle-aged and older individuals [21]. These similar findings were also observed by Blumenthal et al. in his study, wherein the DASH diet compared with exercise is associated with better executive functioning compared to controls after the 6-month intervention [19]. Teixeira et al. [20], with a small sample size of 21 participants, investigated the effects of aerobic and resistance exercise in two groups, systemic arterial hypertension (SAH) and type 2 diabetes mellitus (T2DM) plus SAH. The main finding was that there was an increase in attention and concentration, after a 12-week resistance or aerobic exercise intervention in patients with SAH plus T2DM. One possible explanation for the improvement in the T2DM and SAH groups is that the participants in this group were less focused and attentive before the intervention than the SAH group, therefore it was assumed that patients with T2DM and SAH had a higher proclivity for improvement. Another possibility is that the presence of both diabetes and hypertension causes more cognitive impairment compared to patients with only one condition [24].
There were strong points that support the evidence of our study. First, this was the first systematic review providing complete details on the findings, features, and quality of clinical trials exploring the effect of exercise training on cognition in elderly patients with HTN. Second, the majority of the ­included studies were RCTs. Third, the average quality of included RCTs was good. Fourth, most of the studies had supervised exercise training. There were also a few limitations of this study that should be mentioned. For this systematic review, the search was focused only on two types of exercise intervention. Second, the meta-analysis was not done because of heterogeneous data.

Conclusion

The current systematic review indicates that physical exercise programs might improve cognitive function in people with HTN. Due to limited inclusion criteria and considerable heterogeneity, the findings of the present review should be treated with caution. In order to give further evidence, robust RCTs are required.

List of abbreviations

HTN: Hypertension; NIH: National Institute of Health; BP: Blood pressure; ACC/AHA: American College of Cardiology/American Heart Association; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; CVD: Cardiovascular disease; BDNF: Brain-derived neurotrophic factor; VEGF: Vascular endothelial desired growth factor; IGF-1: Insulin-like growth factor-1; PRISMA: Preferred Reporting Items for Systematic review and Meta-analysis; PROSPERO: International Prospective Register of Systematic Review; RCT: Randomized controlled trial; MMSE: Mini-mental state examination; MTTS: Mental test & training system; CBS: Cambridge Brain Science battery; DASH: Dietary intervention to stop hypertension; CIND: Cognitive impairment without dementia; SAH: Systemic arterial hypertension; T2DM: Type 2 diabetes mellitus

Acknowledgments

The authors acknowledge the support given by the Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia ­Islamia.

Conflict of interest

The authors declared that they have no competing interests.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Corresponding author

Dr. Majumi M. Noohu, Professor
Centre for Physiotherapy & Rehabilitation Sciences,
Jamia Millia Islamia, New Delhi, India
Email: mnoohu@jmi.ac.in
Mobile: 9868 023 378
ORCID ID: 0000-0003-4729-2437

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