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Exercise is Medicine

A Scoping Review of Multiple-modality Exercise and Cognition in Older Adults: Limitations and Future Directions

Boa Sorte Silva, Narlon C. BSc, PhD1,2; Gill, Dawn P. PhD2,3; Petrella, Robert J. MD, PhD, FCFP, FACSM1,2,3,4

Author Information
Current Sports Medicine Reports: August 2020 - Volume 19 - Issue 8 - p 298-325
doi: 10.1249/JSR.0000000000000736



Changes to lifestyle, such as engaging in regular exercise, are postulated as important strategies to prevent or slow the progression of dementia in the aging population (1–3), this includes those with high genetic risk (4). Exercise has been associated with preserved age-related cognitive functioning in observational studies (3,5–8) and has improved cognition (9), as well as shown positive functional (10,11) and structural (12) brain changes in longitudinal interventional studies. Most literature has focused on aerobic exercise training (AET) interventions alone (13), with some evidence suggesting that AET appears to benefit cognition, particularly executive functioning (14), as well as neuroplasticity (15), neural efficiency (16), and hippocampal size in healthy older adults (12) and in those with mild cognitive impairment (MCI) (17).

Despite promising evidence, the impact of AET on cognitive function in the aging population remains equivocal (18). A recent Cochrane review suggests that there is insufficient evidence to conclude that cognitive improvements following AET are solely due to AET itself, even when improvement in cardiovascular fitness is observed (19). The current state of knowledge allows for exploration of exercise interventions that could have additive benefits to cognition beyond AET alone. Encouraging findings have suggested resistance exercise training (RET) as an effective exercise modality to impart benefits to cognition, with positive effects of RET on executive functioning (20,21), as well as brain functional plasticity (22), and white matter structure (23).

Findings from other meta-analytic studies have indicated a lack of consistency across different exercise studies, which could be due to variability in cognitive tests applied, sensitivity of cognitive tests in detecting treatment effects, cognitive and physical health at baseline, as well as characteristics of the exercise programs administered (18,24). Moreover, most studies have failed to comply with current guidelines for exercise in older adults with regard to exercise type, intensity, frequency, and duration (25,26). These guidelines highly emphasize the importance of multiple-modality exercise (MME) programs to enhance overall health and quality of life (26). A recent meta-analysis demonstrated the potential of MME to induce clinically relevant fitness improvements in older adults, including cardiovascular fitness and functional capacity (27). However, no previous literature review has focused solely on investigating effects of MME on cognition and neuroimaging outcomes (28,29).

Therefore, the objectives of this scoping review were to: 1) document the current state of evidence of the impact of MME on cognition and neuroimaging in older adults without dementia; 2) discuss the current state of evidence with regard to exercise prescription and implementation in these studies; and 3) propose future directions for research in the field.


Full details of our methods, including study protocol, search strategy, and data charting can be found in the Supplementary Material ( Briefly, the PICO(T) (population, intervention, comparison, outcome, and [type]) (30) approach was used to develop our research question, while the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (30) were utilized as a guideline in this review. Our research question was as follows: “What are effects of MME interventions aimed at improving cognition and neuroimaging outcomes in older adults without dementia?” Between August and October 2019, we searched the following bibliographical databases for potentially relevant documents: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Scopus. We also contacted authors directly to identify additional relevant material and to further determine eligibility of articles selected for full-text review (30).

We searched the literature for peer-reviewed, published randomized controlled trials (RCTs), and nonrandomized intervention studies (i.e., quasi-experimental) examining the effects of MME interventions on cognition and/or neuroimaging outcomes (see Supplementary Table 1,, for a sample of our search strategy). We defined MME interventions as those that included a combination of AET aimed at improving aerobic capacity or cardiovascular fitness, and RET aimed at improving muscle strength, endurance, or power (26,27). We also included studies that combined AET and RET with balance or flexibility exercises (26,27). Other activities referred to as “warm-up,” “cool-down,” or “recovery” were not considered. Considering the nature of this scoping review, we did not specify minimum or maximum length of exercise programs, whether components of AET or RET were administered in the same session or different sessions, and whether interventions were supervised, home-based, or both (see Supplementary Material,, for details).

In summary, we included studies that met the following inclusion criteria: 1) MME studies combining both AET and RET with or without additional balance/flexibility training, as defined above; 2) included older adults 55 years or older; 3) included individuals with or without cognitive impairment, but not dementia (i.e., cognitively healthy, self-reported cognitive or memory complaints, subjective cognitive/memory decline or impairment [SMI, MCI]); included at least one measure of cognition (e.g., global or domain-specific cognitive function), and/or neuroimaging outcomes relevant to cognitive function (e.g., functional network connectivity, gray matter volume); 5) included a comparator group (i.e., competing treatment group, active control group, or no-treatment control group); 6) published in English between January 1990 and October 2019; and 7) published in a peer-reviewed journal. We also included other articles from the same parent study that reported different relevant outcomes from the original publication; however, we excluded those reporting sensitivity analyses of primary outcomes already reported in the original publication.


Selection of Sources of Evidence

Our search results, including identification, screening, eligibility, and selected articles, are presented in Supplementary Figure 1 ( The original search led to 2945 results, of which remaining 33 studies (original search, 25; added from other sources, 8) were considered eligible for inclusion in this scoping review.

Characteristics of Sources of Evidence

Study design, sample size, and participant characteristics are reported in Table 1. We included 33 studies (31–63), of which 26 were RCT studies (31–37,39,40,42,44–48,50–52,54,55,57,58,60–63) and seven were quasiexperimental studies (38,41,43,49,53,56,59). We included data from 30 original research articles (31–37,39,41–51,53–63) and three articles that were analyses of secondary outcomes (38,39,52). A total of 4458 individuals (excluding counts from secondary outcomes articles) were studied. Sample sizes varied between 19 and 1476 (mean [SD] = 148.6 [270.8]), with age range between 62.2 and 82.3 years (mean [SD] = 72.5 [4.8]) and the majority of participants being females (mean [SD] = 71.3% [16.8]). Most studies included healthy older adults (e.g., preserved physical and cognitive function, n = 13), followed by studies including older adults who were sedentary (n = 8), had cognitive impairment but not dementia (n = 7), were frail (n = 3), had diabetes (n = 1), or were obese (n = 1). Further, considering the study groups (i.e., comparators), the majority of study designs included no-treatment control groups (n = 23), followed by at least one competing treatment group (n = 17) and an active control group (n = 9).

Table 1:
Study and participant baseline characteristics.

MME Protocols

Of the MME protocols included in the 33 studies, 18 involved a combination of AET, RET, plus balance/flexibility training, while 15 studies included AET and RET only (see Table 2). The MME protocols administered varied from 1 d·wk−1 to 7 d·wk−1 (mean [SD] = 3.1 d·wk−1 [1.5 d·wk−1]), and between 30 min·d−1 and 90 min·d−1 (mean [SD] = 62.7 min·d−1 [15.5 min·d−1]) from 1.5 to 24 months (mean [SD] = 6.8 months [6.3 months]). Because of the limited reporting and high inconsistency of measures of exercise intensity, it was not feasible to summarize exercise intensity for all studies; however, intensities varied between low and high for the exercise components. Only 24 studies reported adherence data (i.e., attendance to sessions), ranging from 34.7% to 100% (mean [SD] = 73.9% [15.9%]). Below, we further describe each component individually.

Table 2:
MME intervention details, including frequency, intensity, time and type, and comparator(s).

Aerobic exercise training

Across all studies, the AET component was prescribed on average 3.1 d·wk−1 (SD = 1.6 d·wk−1, n = 33 reported), for an average of 32.6 min·d−1 (SD = 13 min·d−1, n = 27), with studies using low (n = 2), moderate (n = 12), and moderate to high (n = 7) intensity. As mentioned earlier, 21 studies reported measures of AET intensity with high variability in tracking methods, which consisted of rating of perceived exertion (RPE) (n = 7) percentage of maximum heart rate (HR) (n = 6), percentage of HR reserve (n = 3), percentage of HR peak (n = 1), and other methods (n = 4). AET types included continuous endurance activities such as walking, cycling, and dancing (Table 2).

Resistance exercise training

RET was prescribed on average 3.2 d·wk−1 (SD = 1.5 d·wk−1, n = 33), lasting on average 23.6 min·d−1 (SD = 11.3 min·d−1, n = 25), with studies using low to moderate (n = 2), moderate (n = 8), moderate to high (n = 6), and high (n = 2) intensity. Only 18 studies measured RET intensity, using a diversity of methods, which included RPE (n = 8), maximum repetitions (n = 6), and others (n = 4). RET type included bodyweight, machine-based, and free weights, with 1 to 4 sets and 4 to 30 repetitions per muscle group.

Balance and flexibility exercise training

For the 18 studies that included balance and flexibility training components, these were administered on average 3.4 d·wk−1 (SD = 1.8, n = 18), 16.9 min·d−1 (SD = 10.3, n = 13) at low (n = 1) to moderate (n = 2) intensity. Only three studies reported measures of intensity, and these were either verbally described as “moderate intensity” (n = 2) or reported as RPE (n = 1). Balance and flexibility training type involved activities such a static and dynamic balance, postural sway, double- and single-leg stance variations, range of motion exercises, stretching, and mobility of main muscle joints.

Overall Effects of MME on Cognition

Details on study intervention, comparator, cognitive domains and tests, as well as main findings are summarized in Table 3. Also, in Table 4 we report a summary of the tests used to assess cognitive function. Across all studies and comparators, MME showed superior improvements in three measures of global cognitive functioning, seven measures of executive functioning, seven measures of memory, and four measures of processing speed (see Table 4 for more details). When compiling evidence from the 33 included studies, the effects of MME on cognition were considered mixed and heavily dependent on study designs, comparators, and outcomes. Aiming to facilitate coherence and to contextualize the evidence, we stratified our findings based on the differences between MME and comparators (i.e., competing treatment, active control, and no-treatment control groups) on the outcomes of interest (i.e., cognitive domains and tests used in the studies). Evidence from studies that included two or more comparators was considered separately for each applicable comparison, where multiple comparisons were reported by authors (e.g., MME vs active control, or competing treatment). Results are reported in the following subsections.

Table 3:
Summary of study interventions, outcomes, and main findings.
Table 4:
Overall effects of MME on cognitive tests compared with competing treatment, active control, and no-treatment control groups.a

MME compared with competing treatment

A total of 17 studies included one or more competing treatment groups. These included varied forms of cognitive training (n = 8) (36,38–40,42,43,46,53,56), physical training (n = 6) (31,32,35,37,51,58), combined physical and cognitive training (n = 7) (33,36,37,45,46,53,56), or combined physical training and diet (n = 1) (48). In only two studies, MME imparted similar improvements to competing treatment compared with no-treatment control group (42,48). For example, one study reported that MME was of similar effectiveness compared with cognitive training in improving executive functioning and memory (42). Another study showed that MME was equally effective compared with combined physical exercise and diet intervention in improving global cognitive functioning and executive functioning (48).

No other studies reported superiority of MME in improving cognition when compared with competing treatment groups. Furthermore, the overall effects of the competing treatment groups were seen to be either superior to (n = 7) (36,39,40,45,46,53,58), or equivalent (n = 8) (31–33,35,37,43,51,56) to MME in the remaining studies (as reported in Table 3). For studies showing superiority of competing treatment groups, the findings showed that cognitive training alone was superior to MME in improving measures of processing speed (39) and executive functioning (40), and one study showed that physical training (i.e., Tai Chi) was superior to MME in improving measures of executive functioning (58). Furthermore, combining physical (i.e., MME) and cognitive training seemed to yield the greatest benefits in measures of executive functioning (36), processing speed (36,46), and memory (53).

MME compared with active control

Nine of 33 studies included an active control group and reported cognition outcomes (32,34,39,40,47,55,56,58,63). Of these, one study indicated that MME was effective in improving measures of global cognitive function, executive functioning and memory (34), and another study reported improvements in measures of processing speed (47). All other studies did not report results supporting MME imparting superior effects in cognition when compared with active control groups (n = 7) (32,39,40,55,56,58,63).

MME compared with no-treatment control

Twenty-three studies included a no-treatment control group. The overall evidence suggested that MME was effective in improving many aspects of cognitive function. For instance, a number of studies reported improvements in measures of memory (n = 4) (41,42,59,61), processing speed (n = 5) (44,47,60–62), executive functioning (n = 7) (42,44,48,54,60–62) and global cognitive functioning (n = 3) (48,49,57). The remaining studies did not report significant results (n = 11) (31,36,38–40,43,45,46,50,53,56).

MME and Neuroimaging Outcomes

Nine studies included neuroimaging outcomes (34,38–41,51,52,56,59). These involved structural (n = 6) (34,38,41,51,52,59) and functional (n = 1) (41) magnetic resonance imaging (MRI) data, as well as electroencephalogram (EEG, n = 3) (39,40,56) data (see Table 3 for details).

For MRI outcomes, one study reported no significant differences between MME compared with cognitive training and no-treatment control (38) in white matter integrity (i.e., fractional anisotropy). Another study, however, reported MME was associated with improvements in gray matter (occipital and cerebellar regions) and white matter (right temporal and right occipital regions) volumes, compared with dance training (51). Compared with active control groups, two studies reported that MME was associated with greater improvements in hippocampal volume (34,52), and one study reported increased white matter integrity (i.e., fractional anisotropy) and total brain volume (34). Furthermore, compared with no-treatment control groups, MME yielded increases in cortical gray matter (41) and hippocampal volume (59) in two studies.

For EEG outcomes, two studies reported that MME was not effective in improving event-related brain action potentials (i.e., peak and amplitude of activations) in two executive functioning tasks (39,40) compared with cognitive training, active control, and no-treatment control groups. Similarly, another study reported greater improvements in resting-state EEG brain activity (precuneus/posterior cingulate cortex) following a combined cognitive and physical training group compared with MME alone (56).


In this review, we explored the overall effects of MME compared with competing treatment, active control, and no-treatment control conditions in global and domain cognitive function, and neuroimaging outcomes in older adults without dementia. We also had interest in the characteristics of the MME programs administered in the studies (i.e., frequency, intensity, time, and type) with hopes that our findings would aid in informing translation of current findings into practice and provide direction for future research. Our main findings and recommendations are discussed below.

MME and Cognitive Function

Our findings indicated that when compared with competing treatment groups, apart from two studies (42,48), the majority of studies indicated that MME was inferior to competing treatments in improving cognition outcomes (31–33,35–40,43,45,46,51,53,56,58). Similarly, only two studies reported that MME was superior to active control groups in improving cognition (34,47), while the remaining studies including active control groups did not find MME to be superior (32,40,55,56,58,63). The only scenario in which MME was primarily effective in improving global and domain-specific cognitive function was when compared with no-treatment control groups (41,42,44,47–49,54,57,59–62). Moreover, as reported in Table 4, most studies investigated changes in measures of executive functioning, followed by measures of memory, global cognitive function, and processing speed. In all of these measures, apart from one study in which processing speed (47) was improved compared with active control groups, MME was only superior in improving global or domain-specific cognitive function when compared with no-treatment control groups.

Important considerations must be made when discussing these findings. Many studies included competing treatment groups that combined both cognitive and physical training (33,36,37,45,46,53,56). Considering the studies showing superiority of combining both treatments when compared with MME alone, we observed improvements in measures of executive functioning (36), processing speed (36,46), and memory (53). One confounding aspect of these findings is that by receiving both physical and cognitive training, study subjects would receive prolonged exposure to treatment effects during each session. As identified in the study by Damirchi and colleagues (36), participants in the combined treatment group received prolonged intervention (90 to 120 min·d−1, 3 d·wk−1) compared with the MME group (60 min·d−1, 3 d·wk−1). Similarly, two studies showed superiority of cognitive plus physical training sessions lasting longer (i.e., min·d−1) than the MME session (i.e., Linde et al (46) and Shah et al (53), see also Table 3 for more details). Therefore, it remains to be investigated whether a combination of cognitive and physical training can impart improvements to cognition because of intrinsic aspects of these interventions only or because of prolonged exposure to treatment stimuli.

Nevertheless, considering that MME was not superior to active control groups in seven (32,39,40,55,56,58,63) of nine tudies included, we also must consider other factors influencing the effects of MME beyond prolonged exposure to treatment. Confounding effects of socialization, for instance, are present when these interventions are administered in sessions with multiple participants exercising together. In fact, social interaction may provide significant cognitive stimulation (55) and partially account for improvements in cognition (64,65). Furthermore, in a previous review (28), greater effect sizes were observed following exercise in older adults compared with no-treatment control groups, but not in comparison to active control groups (28). Therefore, the lack of superiority of MME when compared with active control groups could be attributed to effects of socialization.

Our findings suggested that only when compared with no-treatment control groups, MME yielded improvements in cognition (i.e., memory (41,42,59,61), processing speed (44,47,60–62), executive functioning (42,44,48,54,60–62) and global cognitive functioning (48,49,57)). These findings suggest the potential of MME to impart improvements in cognition in individuals with different clinical characteristics, given that the studies included healthy or sedentary older adults (41,42,59–62), as well as frail (44,47,57), obese (48), and MCI (49) individuals. Nevertheless, caution must be exercised when interpreting these findings, as essential limitations must be considered. For instance, three of the included studies were nonrandomized (i.e., quasi-experimental), and therefore, bias is inflicted in study results owing to confounding factors (e.g., selection bias). Another confounding variable introduced by including no-treatment control groups is that participants exposed to MME interventions also are exposed to other factors, such as attention and social interaction (as mentioned above). This is a crucial aspect of the studies included, since six (42,44,47,49,57,60) of the included studies explicitly reported that the MME sessions were administered in groups of at least three participants.

Altogether, the literature suggests MME may be an effective strategy to improve global and domain-specific cognitive function; albeit, there is limited evidence from studies including active control or competing treatment groups. Considerations and limitations regarding the MME protocols administered in these studies are discussed in the subsequent sections.

Effects of MME in Neuroimaging Outcomes

Evidence from nine studies suggested mixed effects of MME on white matter structure, but more consistent effects on cortical and subcortical gray matter. Fissler and colleagues (38) reported no differences in white matter integrity (i.e., fractional anisotropy) in older adults with SMI following cognitive training or MME, compared with a no-treatment control group. Conversely, Callisaya and colleagues (34) reported improvements in fractional anisotropy in older adults with diabetes compared with an active control group, and Rehfeld and colleagues (51) noted greater increases in white matter in temporal and occipital lobes following MME compared with dance training. Dance training, nonetheless, yielded greater changes in the white matter of other brain regions (see Table 3) suggesting training-specific adaptations.

Although the evidence is limited, these findings suggest that MME may be effective in imparting improvements in white matter; however, the extent to which these improvements are superior to other interventions (e.g., dance training or cognitive training) warrants further exploration. Some relevant contrasts among these studies also must be considered. Fissler and colleagues (38) included older adults with SMI, a marker of increased risk of dementia (66), while Callisaya (34) studied older individuals with diabetes—comprising a different risk profile for dementia (67) — and Rehfeld and colleagues included only healthy individuals (51). The most notable difference between studies, however, could be the length of these programs, with one lasting only 10 wk (38), while the other two studies (34,51), which showed in part positive effects of MME on white matter outcomes, lasted 6 months. As such, longer intervention periods may result in greater positive changes in white matter.

Regarding changes in the gray matter of cortical and subcortical structures, compared with no-treatment control groups, Ji and colleagues (41) reported that MME was associated with increases in cortical gray matter, while Teixeira and colleagues (59), reported increases in hippocampal volume. In comparison to active control groups (34,52), MME was associated with greater increases in total brain volume (34) and hippocampal volume (34,52). Furthermore, among the studies included, Ji and colleagues (41) were the only ones to investigate functional connectivity changes via fMRI. Using a resting-state fMRI protocol, the authors reported increased functional connectivity between the posterior cingulate cortex/precuneus and the right striatum, and other regions compared with controls — while controls suffered atrophy of the striatum region, suggesting protective effects of MME.

Altogether, the main findings of MRI and fMRI studies point toward MME imparting positive changes in brain function and structure, particularly marked by multiple studies reporting significant increases in hippocampal volume (34,52,59). Clinically, these results could have relevance to prevent and/or delay onset of cognitive impairment. Both hippocampi are implicated in memory function (68–70), and are hallmark regions where pathophysiological changes in MCI and early/prodromal stages of Alzheimer’s disease occur (e.g., amyloid beta deposition) (71), including cortical atrophy preceding Alzheimer’s disease diagnosis (72). Nonetheless, three of the studies reporting positive effects of MME were nonrandomized interventions (38,41,59) and their findings should be interpreted with caution.

Finally, three studies explored EEG outcomes as surrogate measures of brain activity (39,40,56). All three studies included competing treatment groups and their results suggested that MME was not superior to other treatment conditions in improving resting-state and task-based brain activity. For instance, in an early study Gajewski and Falkenstein (39) reported that cognitive training yielded higher improvements in event-related brain action potentials associated with response selection, allocation of cognitive resources, and error detection compared with MME. Similarly, in a secondary study, the same authors (40) reported improvements in underlying processing associated with working memory following cognitive training only. Accordingly, Styliadis and colleagues reported additive effects of combining cognitive and physical training in resting-state electrophysiological brain activity in the precuneus/posterior cingulate cortex compared with MME alone (56). Overall, these findings suggest that MME alone has limited influence in brain activity measured via EEG outcomes when compared with competing treatment groups. Owing to limited literature included in this review, this topic needs to be further explored.

Recommendations and Future Directions

One key aspect to be further investigated is whether compliance with international guidelines for exercise in older adults and increasing adherence to exercise will aid in strengthening the effects of MME on cognitive function. For example, for the studies included in this review, the average frequency of MME sessions was 3.1 (SD = 1.5) d·wk−1, lasting on average 62.7 (SD = 15.5) min·d−1. However, the average time spent in each MME component was 32.6 (SD = 13) min·d−1 for AET, 23.6 (SD = 11.3) min·d−1 for RET, and 16.9 (SD = 10.3) min·d−1 for the balance/flexibility component. In this context, the average time per component is relatively low compared with previous recommendations (26,73). It is important that future research addresses whether complying with recommendations would yield greater benefits above and beyond confounding variables influencing cognition (e.g., socialization). This is pertinent when contemplating that previous studies have provided strong evidence for the positive effects of AET (15) and RET (21) on cognition. These are examples of well-conducted RCTs, with detailed exercise programs, and measures of cognitive function sensitive to the effects of exercise (15,21). Consequently, with a detailed MME program, administered with appropriate frequency, duration, and intensity, it is plausible to expect additive effects of combining AET and RET, and potentially balance/flexibility training (1,74).

Finally, because of the heterogeneity across studies, it was challenging to gather and harmonize information on the elements of the exercise programs administered (i.e., frequency, intensity, time, and type). Future studies should consider a standardized and detailed method of reporting exercise training protocols, which will facilitate appreciation and understanding of the effects of exercise on variables of interest (27). To this end, we suggest reporting on exercise training variables following previous recommendations (26,27), including the following: a) exercise frequency (e.g., d·wk−1); b) objective or subjective measures of intensity (e.g., target HR, RPE, maximum repetitions, etc.); c) time allocated to each component (e.g., min·d−1) and d) type of exercise administered (e.g., running, walking, machine-based, bodyweight). If with stronger study designs, clearer training methodology, and well-defined study populations, MME is proven to be efficient to improve brain health, it will then be plausible to discuss long-term effects and follow-ups, feasibility, and translation of these programs in real-world community settings (27).


Our findings indicated that MME has the potential to impart positive changes in global and domain-specific cognitive function, as well as white matter, cortical gray matter, and hippocampal volume when compared with no-treatment control groups. The lack of superiority of MME when compared with competing treatment or active controls suggests that extrinsic factors, such as socialization, could yield improvements independent of MME effects. Summary data from the MME protocols administered, including frequency, intensity, and time of MME programs administered did not seem to be fully aligned with current guidelines for exercise for older adults, which could have hindered MME effects. It is plausible that combining different treatment conditions may provide additive effects to cognitive function; however, the feasibility of such programs to be translated to real world settings remains to be explored in future research.

The authors declare no conflict of interest and do not have any financial disclosures.


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