Ageing Research Reviews 15 (2014) 61–75

Contents lists available at ScienceDirect

Ageing Research Reviews

journal homepage: www.elsevier.com/locate/arr

Review

Effects of combined cognitive and exercise interventions on cognition

in older adults with and without cognitive impairment: A systematic
review
Lawla L.F. Law a,∗ , Fiona Barnett b , Matthew K. Yau a , Marion A. Gray c
a
Occupational Therapy Discipline, School of Public Health, Tropical Medicine & Rehabilitation Sciences, James Cook University, Queensland, Australia
b
Institute of Sport & Exercise Science, School of Public Health, Tropical Medicine & Rehabilitation Sciences, James Cook University, Queensland, Australia
c
Cluster for Health Improvement, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Global concern on the potential impact of dementia is mounting. There are emerging calls for studies in
Received 5 November 2013 older populations to investigate the potential benefits of combining cognitive and exercise interventions
Received in revised form 25 February 2014 for cognitive functions. The purpose of this systematic review is to examine the efficacy of combined
Accepted 28 February 2014
cognitive and exercise training in older adults with or without cognitive impairment and evaluate the
Available online 12 March 2014
methodological quality of the intervention studies. A systematic search of Cinahl, Medline, PsycINFO,
ProQuest, EMBASE databases and the Cochrane Library was conducted. Manual searches of the reference
Keywords:
list from the included papers and additional internet searches were also done. Eight studies were identi-
Systematic review
Cognitive impairment
fied in this review, five of which included a cognitively impaired population and three studies included
Healthy older adults a cognitively healthy population. The results showed that combined cognitive and exercise training can
Combined intervention be effective for improving the cognitive functions and functional status of older adults with and without
Dual-task exercise cognitive impairment. However, limited evidence can be found in populations with cognitive impairment
when the evaluation included an active control group comparison. Further well-designed studies are still
needed to explore the potential benefits of this new intervention paradigm.
© 2014 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.1. Search strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.2. Inclusion/exclusion criteria and selection process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.3. Data extraction and analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.4. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.1. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.2. Study characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.3. Participants and settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.3.1. Studies with cognitively healthy participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.3.2. Studies with cognitively impaired participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.4. Intervention duration and group comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.4.1. Studies with cognitively healthy participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.4.2. Studies with cognitively impaired participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

∗ Corresponding author at: Occupational Therapy Discipline, James Cook Drive, Douglas; School of Public Health, Tropical Medicine and Rehabilitation Sciences, Rehabili-
tation and Exercise Sciences Building, James Cook University, Townsville, QLD 4811, Australia. Tel.: +61 7 47816678.
E-mail addresses: lan.law@my.jcu.edu.au (L.L.F. Law), fiona.barnett@jcu.edu.au (F. Barnett), matthew.yau@jcu.edu.au (M.K. Yau), marion.gray@usc.edu.au (M.A. Gray).

http://dx.doi.org/10.1016/j.arr.2014.02.008
1568-1637/© 2014 Elsevier B.V. All rights reserved.

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 62 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75

3.5. Intervention programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

3.5.1. Studies with cognitively healthy participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.5.2. Studies with cognitively impaired participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.6. Outcome measures and intervention effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.6.1. Studies with cognitively healthy participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.6.2. Studies with cognitively impaired participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
3.7. Methodological quality of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
4. Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
4.1. Comparison and control group design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
4.2. Study population screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
4.3. Training sequence in combined intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
4.4. Dual-task component . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
4.5. Intervention period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
4.6. Outcome measure selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
4.7. Visual-spatial component . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
4.8. Generalization of training effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
4.9. Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Source of funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

1. Introduction peripheral risk factors (e.g. hypertension) for cognitive decline

(Cotman et al., 2007; Pereira et al., 2007).
The increasing prevalence of cognitive impairment with age Whilst the uniqueness of exercise-induced effects to enhance
intensifies the potential impact upon global health and health care. brain health and cognitive functions through multiple routes is
It has been projected that there will be 7.7 million new cases evident, results of intervention studies on single exercise interven-
of dementia each year, implying a new case of dementia every tion are disappointing (Busse et al., 2009; Etnier et al., 2006). A
4 s (WHO and ADI, 2012). The World Health Organization (WHO) recent systematic review showed that strong evidence to support
has urged global efforts to take a serious focus on the potential the effects of exercise interventions on cognitive functions of older
impacts of dementia on the societal and health care systems world- adults is still lacking (Snowden et al., 2011).
wide. Individuals with mild cognitive impairment (MCI) are at high It has been proposed that exercise has to occur in the context
risk of progressing to Alzheimer’s diseases and other dementias, of a cognitively challenged environment in order to be effective for
with reported conversion rate of 50% in 2–3 year (Amieva et al., inducing neural and cognitive benefits rather than exercise alone
2004) and even up to 60–100% in 5–10 years (Morris et al., 2001; (Fabel and Kempermann, 2008; Fabel et al., 2009). Studies also
Petersen, 2004). Addressing the lack of pharmacological treat- have found that a combination of exercise and an enriched envi-
ment for individuals with MCI (Alzheimer’s Association, 2013), it ronment induces more new neurons and benefits the brain greater
is critical to explore the potential effects of non-pharmacological than either exercise or an enriched environment alone (Fabel and
interventions. Kempermann, 2008; Fabel et al., 2009; Olson et al., 2006). An ani-
The benefits of exercise on cognition are widely recognized mal study reported significant improvements in cognitive ability
(Cotman and Berchtold, 2007; Kramer and Erickson, 2007; van when combined physical and cognitive training was undertaken
Praag, 2009). Animal studies have consistently shown exer- (Langdon and Corbett, 2012). A combination of exercise and cogni-
cise increases cell proliferation and neurogenesis in the dentate tive interventions, either sequentially or simultaneously, appears
gyrus of the hippocampus (Fabel et al., 2003; Kronenberg et to have the potential effect to maintain or improve cognitive func-
al., 2006), an important brain area for learning and memory. tions (Langdon and Corbett, 2012; Schaefer and Schumacher, 2011).
Exercise regulates a number of growth factors such as brain- Indeed, there are emerging calls for studies in older populations
derived neurotrophic factor (BDNF), which plays a crucial role to investigate the potential benefits of combined cognitive and
in neuroprotection and synaptic plasticity (Adlard et al., 2005; physical interventions to accomplish an optimal outcome (Amoyal
Vaynman et al., 2004); insulin-like growth factor 1 (IGF-1), which and Fallon, 2012; Kraft, 2012; Rebok, 2008; Thom and Clare,
promotes neuronal growth and improves cognitive performance 2011).
(Cotman and Berchtold, 2002; Liorens-Martin et al., 2010); vascular The aims of this review were: (1) to assess the efficacy of
endothelial growth factor (VEGF), which stimulates angiogene- combined cognitive and exercise training to improve cognitive
sis and vasculogenesis (Tang et al., 2010; Zhang et al., 2013) functions in older adults with and without cognitive impairment;
and promotes brain ischemic tolerance (Zhang et al., 2011). Fur- (2) to examine the methodological quality of the included studies;
thermore, exercise reduces inflammatory cytokines and oxidative and (3) to summarize the latest results on combined cognitive and
stress, which suggests anti-inflammatory and antioxidant effects exercise training in older adults with or without cognitive impair-
on the brain (Pervaiz and Hoffman-Goetz, 2011; Santin et al., ment.
2011). For the purpose of this review, combined cognitive and exercise
Colcombe et al. (2006) also found that exercise correlates with interventions are structured interventions that combine cognitive
an increase in brain volume over the frontal, parietal, and tem- training and exercise, either conducted in sequence or simultane-
poral cortices in humans. Studies also have shown that exercise ously under dual-tasking paradigms. Cognitive training are defined
can promote cerebral blood flow which enhances neurogenesis as structure repeated practice on tasks with an inherent problem,
and improves learning (Farmer et al., 2004; van Praag et al., 2005), using standardized tasks targeting specific cognitive domains
as well as promotes cardiovascular fitness and therefore reduces and/or teaching strategies and skills in order to optimize cognition

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 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75
and functioning (Clare and Woods, 2003; Martin et al., 2006).
Exercise is defined as a form of physical activity that is planned,
structured and repetitive over an extended period of time, with
the purpose to improve fitness, performance or health (Casperson
et al., 1985).
2. Methods
2.1. Search strategies
A systematic computer-based search of Cinahl, Medline,
PsycINFO, ProQuest, EMBASE databases and the Cochrane Library
was conducted for the time period between January 1995 and
June 2013. The following search terms were used: (combine*
interventions OR rehabilitation OR dual-task OR multi-modal)
AND (exercise OR physical activity OR resistance training OR
endurance training) AND (cognitive training OR cognitive-motor
OR mental) AND (cognitive impairment OR cognit* OR dement* OR
Alzheimer*). The search was limited to publications in English. All
reference lists in selected journal articles were further screened and
additional internet searches using the same search terms were con-
ducted on Google Scholar to identify additional potentially relevant
articles.
2.2. Inclusion/exclusion criteria and selection process
As recommended in the Cochrane Handbook of Systematic
Review of Interventions, two reviewers (LL and FB) independently
screened the titles and abstracts to identify relevant articles and
potentially relevant studies. Disagreements between the review-
ers about inclusion were resolved through discussion (Higgins and
Green, 2011). Studies were included in this review if they met the
following criteria: (1) design: randomized controlled trial (RCT)
or non-randomized controlled trial (NRCT); (2) sample popula-
tion: older adults (aged 60 and older) with or without cognitive
impairment/decline or dementia but no mental or neurological dis-
orders other than dementia, such as stroke or major depression;
(3) intervention: combined cognitive and exercise training; and (4)
outcome: cognitive functions assessed using neuropsychological
tests as primary or secondary outcomes. Articles were excluded
if they were: (1) non-intervention studies; (2) theoretical articles
or descriptions of treatment approaches; (3) review articles; (4)
unpublished studies, abstracts or dissertations; (5) articles with-
out adequate specification of interventions; (6) non-peer reviewed
articles and book chapters; and (7) non-English language articles.
Multicomponent intervention studies which did not distinguish the
contribution of combined cognitive and physical exercise compo-
nent on the effects were also excluded.
2.3. Data extraction and analysis
Data were extracted using a data extraction form for the
description of methodology and important trial characteristics
including study populations, intervention type, training delivery,
volume of training, outcome measures, and follow-up. This review
focused on a description of the studies and their results, and on
qualitative synthesis of the findings. However, Cohen’s d effect
sizes (Cohen, 1988) for cognitive and functional outcomes at
pre- and post-intervention were derived on the basis of reported
statistics. The standard effect sizes were calculated by dividing
the mean score differences of the combined intervention and
control groups in each study by the pooled estimate standard
deviation for the two groups. When means and standard devi-
ations were not available, effect sizes were computed from the
reported P-value or F-values reported in the study (Thalheimer
and Cook, 2002). The 95% confidence intervals (CIs) were also
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63
derived to compare groups before and after the intervention.
(Practical effect size calculator retrieved March 9, 2013 from
http://gunston.gmu.edu/cebcp/EffectSizeCalculator/d/means-and-
standard-deviations.html). Effect sizes were interpreted as small,
d = 0.20; medium, d = 0.50; or large, d = 0.80 (Cohen, 1988).
2.4. Quality assessment
Methodological quality of the included studies was indepen-
dently assessed by 2 reviewers (LL and FB) using a 13-item checklist
modified from the Delphi list (Verhagen et al., 1998), the Physio-
therapy Evidence Database (PEDro) scale (Maher et al., 2003) and
the “Design-specific criteria to assess for risk of bias” by the Agency
for Healthcare Research and Quality (AHRQ) (Viswanathan et al.,
2012). Any disagreements identified between the two reviewers
were resolved by a third reviewer (MY) as a final decision. Details
of the quality checklist and the rating criteria are presented in
Appendix 1.
All items on the list applied to both RCT and non-RCT. A qual-
ity score ranging from 0 to 13 was calculated for each study.
The scale is only used to provide a quantitative reference of the
degree/likelihood that the reported methodology and results of the
included studies are approaching free of bias. As a summary on
quality, a study was defined as: (1) High quality when presenting a
positive score on 10 or more items; (2) Medium quality when pre-
senting a positive score on 7–9 items and (3) Low quality when
presenting a positive score on <7 items (<50% of the maximum
attainable score) (Verhagen et al., 2007; Viswanathan et al., 2012).
3. Results
3.1. Study selection
A summary of the selection process is illustrated in Fig. 1. The
initial database search identified a total of 572 potentially relevant
citations with 73 from Cinahl, 41 from Medline, 230 from PsycINFO,
35 from ProQuest, 89 from EMBASE and 104 from Cochrane Library.
After excluding duplicated articles, 474 citations were left. All titles
and abstracts were screened according to the inclusion/exclusion
criteria described and 461 articles were discarded.
The common reasons for exclusion of articles were the follow-
ing: the interventions were not combined exercise and cognitive
intervention (80), they were not intervention studies or were
reviews/theoretical articles (158), they did not include the target
population under this review (213), and did not include cognitive
outcomes (10). Full texts of 13 articles were retrieved from the
initial database search and carefully examined. Cross-referencing
led to three more articles and the internet search using the same
search terms identified three more articles. A total of 19 articles
were finally retrieved for full text screening.
After further screening with the inclusion/exclusion criteria, 11
articles were discarded as four articles used exercise only or did not
use combined exercise and cognitive interventions (Burgener et al.,
2008; Heyn, 2003; Komai and Yamada, 2012; Onor et al., 2007);
three were on-going studies (Gates et al., 2011; Gillette-Guyonnet
et al., 2009; O’Dwyer et al., 2007); one did not include cognitive
outcomes (Doi et al., 2013); one was a second paper reporting a data
set from the same study (Fabre et al., 1999); one was a repeat of the
online first view (Coelho et al., 2012); and one did not distinguish
the effects of the combined cognitive and physical training in the
study (Shatil, 2013). A total of eight studies were therefore included
for this review.
3.2. Study characteristics
Of the eight studies reviewed, three studies (1 RCT and 2 non-
RCTs) included a population of cognitively healthy older adults
 64 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75
Fig. 1. Selection process of the systemic review.
(Fabre et al., 2002; Legault et al., 2011; Oswald et al., 2006). Four
studies (2 RCT and 2 non-RCTs) included a population of people
with cognitive impairment including dementia (Schwenk et al.,
2010), Alzheimer’s disease (AD; Coelho et al., 2012) and mild cog-
nitive impairment (MCI; Kounti et al., 2011; Suzuki et al., 2012).
One RCT included a population of people with cognitive complaints
(Barnes et al., 2013).
Cognitive complaints have been found to be associated with
decreased performance in objective memory and executive func-
tion tests (Rouch et al., 2008). Neuroimaging studies have also
shown people with subjective cognitive complaints have structural
brain changes similar to persons with mild cognitive impairment
and different from those of healthy people (Saykin et al., 2006;
van der Flier et al., 2004). Therefore, for this review, the identi-
fied study which included a population with cognitive complaints
(Barnes et al., 2013) was reported under the studies with cogni-
tively impaired population. Tables 1 and 2
illustrate the intervention characteristics of the reviewed stud-
ies in cognitively healthy populations and older adults with
cognitive impairment respectively. Tables 3 and 4
illustrate the study characteristics as reported by outcome
measures and effect sizes of the reviewed studies.
3.3. Participants and settings
3.3.1. Studies with cognitively healthy participants
The number of cognitively healthy people (total 480) in the stud-
ies varied from 32 (Fabre et al., 2002) to 375 (Oswald et al., 2006).
The mean age of the study populations ranged from 61.9 (Fabre
et al., 2002) to 79.5 (Oswald et al., 2006) years. Only one study per-
formed cognitive screening using the modified Mini-mental Status
Examination (modified MMSE) at baseline (Legault et al., 2011).
One study was conducted in France, one in Germany and one in
United States.
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3.3.2. Studies with cognitively impaired participants
The number of people with cognitive impairment (total 322)
varied from 27 (Coelho et al., 2012) to 126 (Barnes et al., 2013).
The mean age of the study populations ranged from 67.8 (Kounti
et al., 2011) to 82.3 (Schwenk et al., 2010) years. Four studies used
the Mini-mental Status Examination (MMSE) score as a baseline
measure of cognitive function, with an average score of 22.5 ranging
from 15.4 (Coelho et al., 2012) to 29.6 (Kounti et al., 2011). One
study used the modified MMSE score with a mean score of 94.4
(Barnes et al., 2013). One study was conducted in Germany, one in
Brazil, one in Greece, one in United States and one in Japan.
3.4. Intervention duration and group comparison
3.4.1. Studies with cognitively healthy participants
Table 1 presents the characteristics of interventions for cogni-
tively healthy older adults. The total time of intervention varied
from 38 (Fabre et al., 2002) to 67.5 (Oswald et al., 2006) hours,
while the intervention duration ranged from two months (Fabre
et al., 2002) to one year (Oswald et al., 2006).
Two studies were four-arm controlled trials comparing the com-
bined cognitive and exercise training, single cognitive training,
single exercise training and control groups (Fabre et al., 2002;
Legault et al., 2011). Fabre et al. (2002) used no treatment control
and Legault et al. (2011) used health education control. One study
was a six-arm controlled trial comparing combined cognitive and
physical training, combined psycho-educational and physical train-
ing, single cognitive training, single psycho-educational training,
single physical training and no treatment control groups (Oswald
et al., 2006).
3.4.2. Studies with cognitively impaired participants
Table 2 presents the intervention characteristics for older adults
with cognitive impairment. The total time of intervention varied
from 30 (Kounti et al., 2011) to 120 (Suzuki et al., 2012) hours, and
the intervention duration ranged from three months (Barnes et al.,
2013; Schwenk et al., 2010) to one year (Suzuki et al., 2012).
One study (Barnes et al., 2013) was a four-arm controlled trial
comparing the combined mental activity and exercise training;
mental activity and exercise control; mental activity control and
exercise; and mental activity control and exercise control. Four
studies were two-arm controlled trials comparing a single dual task
intervention group with a control group, including motor placebo
(Schwenk et al., 2010), no treatment (Coelho et al., 2012), waitlist
(Kounti et al., 2011) and health education (Suzuki et al., 2012).
3.5. Intervention programs
3.5.1. Studies with cognitively healthy participants
All three reviewed studies used combined cognitive and
physical training sessions in sequence. All interventions were
center-based, with one study also including a home-based walk-
ing program (Legault et al., 2011). The content of cognitive training
included computer-based memory training (Legault et al., 2011);
processing speed, attention and memory training (Oswald et al.,
2006) or structured multicomponent cognitive training (Fabre
et al., 2002). In regards to the exercise sessions, two studies used
aerobic exercise (Fabre et al., 2002; Legault et al., 2011); and one
study used balance and flexibility training (Oswald et al., 2006).
3.5.2. Studies with cognitively impaired participants
Of the five reviewed studies, four studies used dual-task training
within the exercise sessions (Coelho et al., 2012; Kounti et al., 2011;
Schwenk et al., 2010; Suzuki et al., 2012). One study used combined
cognitive and physical training by including an independent home-
based computer cognitive training plus a supervised center-based
 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75 65

Table 1
Intervention characteristics of studies in cognitively healthy populations.

Study Design Participants Interventions Total intervention Control/comparison (total

hours (h) hours)

Fabre et al. (2002) Non-RCT N = 32; France Supervised group 38 h CG: No training, but meeting
IG/CG/CG*1/CG*2: 8/8/8/8 Combined Aerobic (AT) & Mental for leisure activities
training (MT) CG*1: Aerobic training (AT)
? Sequence CG*2: Mental training (MT)
Mean age (years):
IG/CG1/CG*1/CG*2: AT: brisk walking and/or jogging 16 h
61.9/65.7/65.4/67.5 (intensity determined by
ventilation threshold
2×/week for 60 min/session for 2
months
MMSE score: not conducted
MT: eight themes: perceptive 12 h
activities, attention, intellectual
structuration, association and
imagination, language, spatial
marks, temporal marks and
associated recruiting.
1×/week; 90 min/session for 2
months

Legault et al. (2011) RCT N = 73; United States Supervised group CG: Health education;
IG/CG/CG*1/CG*2: 19/18/18/18 Combined Cognitive (CT) & 62 h 1×/week
Physical training (PT); CG*1: Cognitive training (CT)
PT followed CT on the same day.
Mean age (years): CT: Computer-based memory 20 h
training;
IG/CG/CG*1/CG*2: 24 sessions (2×/week, for 2
76.9/75.4/76.0/77.5 months + 1×/week for 2 months);
40–50 min/session
Modified MMSE: PT: aerobic & flexibility training 42 h
(walking/stationary cycling)
IG/CG/CG*1/CG*2: 32 center-based sessions (2×/week
94.6/94.3/95.6/94.6 for 4 months); 60 min/session; plus
150 min/week home-base walking
sessions for the first month

Oswald et al. Non-RCT N = 375; Germany Supervised group CG: No treatment

(2006) IG/CG/CG*1/CG*2/CG*3/CG*4:
32/103/57/32/115/36
Mean age (years): 79.5
MMSE score: Not conducted
Combined Cognitive (CT) & 67.5 h CG*1: Cognitive training (CT)
Physical training (PT) CG*2: Physical training (PT)
PT was carried out before CT or Psy CG*3: Psychoeducational
T in a part of the training groups training (Psy T; 45 h)
and following CT or Psy T in psychoeducation, group
another part of the groups discussion, role playing
CT: Visual search tasks; 45 h CG*4: Combined Psy T + PT
verbal/visual memory tasks; (67.5 h)
memory strategies
30 sessions (1×/week over 1 year);
90 min/session
PT: Balance, perceptual, motor 22.5 h
coordination flexibility; gymnastic
exercises and games
30 sessions (1×/week over 1 year);
45 min/session

IG: intervention group; CG: control group; CG*: comparison group.

MMSE: Mini-mental State Examination

exercise training (Barnes et al., 2013). Regarding the exercise com-
ponents, three studies included aerobic and strength training which
targeted exercise intensity (Barnes et al., 2013; Coelho et al., 2012;
Suzuki et al., 2012); one study included resistance and balance
training (Schwenk et al., 2010) and one study included walking and
movement-based exercise (Kounti et al., 2011). In regards to the
dual-task components, three studies (Coelho et al., 2012; Schwenk
et al., 2010; Suzuki et al., 2012) involved performing motor tasks
(e.g. walking, throwing/bouncing ball) and concurrent cognitive
tasks (e.g. calculation, naming or reacting to verbal command).
One study (Kounti et al., 2011) conducted dual-task training using
cognitive-based kinetic exercise with visual and verbal cues (e.g.
wreath, boards with letters, balls and rings).
3.6. Outcome measures and intervention effects
3.6.1. Studies with cognitively healthy participants
Table 3 presents the outcomes, key findings and effect sizes of
the reviewed studies in cognitively healthy persons. Two studies
measured general cognitive functions, with one study reporting
significant improvement in the cognitive function composite score,
and sustained at five-year follow-up (Oswald et al., 2006). Two
studies assessed memory performance, with one study showing
a significant effect on the Wechsler Memory Scale (Fabre et al.,
2002). One study also included subjective measures of cognitive
impairment, functional status and everyday competence (Oswald
et al., 2006) and found significant improvements in cognitive

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66
Table 2
Intervention characteristics of studies in cognitively impaired populations.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.

Study Design Participants Interventions Total intervention hours (h) Control/comparison (total hours)

Barnes et al. (2013) RCT (Rater-blind) N = 126; older adults with memory Independent Home-based + center-based
complaints; USA supervised class
IG/CG/CG*1/CG*2: 32/31/31/32 Combined Mental Activity (MA-I) & Aerobic
Mean age: 73.4 years Exercise (Ex-I)
Modified MMSE: MA-I: independent computer-based training at
IG/CG/CG*1/CG*2: 94.0/94.4/94.6/94.8 home for visual and auditory processing
12 weeks; 60 min/day; 3 days/week
EX-I: aerobic & strength training
12 weeks; 60 min/day; 3 days/week
CG: Mental activity (MA-I) &
Exercise control (EX-C;
72 h stretching, toning) (72 h)
CG*1: Aerobic exercise (EX-I) &
36 h Mental activity control (MA-C;
DVD educational lecture) (72 h)
CG*2: Exercise control (EX-C) &
36 h Mental activity control (MA-C)
(72 h)

Coelho et al. (2012) Non-RCT N = 27; Alzheimer’s disease (AD); Brazil Supervised group CG: No intervention

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75

IG/CG: n = 14/13 Multimodal Dual-task exercise: 48 h
Mean age (years): Strength/resistance training, moderate
IG/CG: 78.0/77.1 intensity aerobic capacity/balance training,
MMSE score: motor activities (bouncing ball, walking,
IG/CG: 19.5 ± 4.1/19.0 ± 2.9 exercise with weights); plus simultaneous
cognitive tasks (naming/words generation or
reacting to verbal command)
16 weeks; 3×/week; 60 min/session

Kounti et al. (2011) Non-RCT N = 58; mild cognitive impairment; Greece Supervised group CG: Wait-list control
(Rater-blinded) IG/CG: 29/29 Dual-task kinetic exercise: 30 h
Mean age (years): visual-active movement, visual-walking,
IG/CG: 70.48/67.83 visual-balance, visual-fine motor,
MMSE score: auditory-free movement
IG/CG: 28.03 ± 1.61/27.34 ± 1.83 20 sessions, 1×/week; 90 min/session

Schwenk et al. (2010) RCT N = 61; dementia; Germany Supervised group CG: Motor placebo group: low
Double-blinded IG/CG: 26/35 Dual-task exercise 48 h intensity exercise including
(Rater & subject Mean age (years): Progressive resistance and functional balance flexibility exercise,
blinded) IG/CG: 80.4/82.3 training; then progress to specific dual-task calisthenics, and ball games
MMSE score: training (e.g. walking while throwing while sitting (24 h)
IG/CG: 21.0 ± 2.9/21.7 ± 2.9 ball/calculation; 10–15 min individual)
12 weeks; 2×/week; 120 min/session

Suzuki et al. (2012) RCT (Rater-blind) N = 50; amnestic mild cognitive Supervised group Health education; 3 sessions
impairment; Japan Multicomponent dual-task exercise: 120 h over 12 months
IG/CG: 25/25 Moderate intensity aerobic exercise, muscle
Mean age: 76 ± 7.1 years; strength, postural balance & dual task training;
MMSE score: plus self-monitoring daily home-based
IG/CG: 26.8 ± 1.8/26.6 ± 1.6 exercise (outdoor walking)
80 sessions over 12 months; 2×/week;
90 min/session

IG: intervention group; CG: control group; CG*: comparison group.

MMSE: Mini-mental State Examination.
 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75 67

impairment (Sandoz clinical assessment geriatrics) at follow-up as

d = 1.29 (0.21–2.36)
well as in functional status (Independent living composite score)

Data not available

Post-intervention
at post-intervention and at five-year follow-up. Only one study

for calculation
assessed executive functions but found no effects (Legault et al.,
2011).

3.6.2. Studies with cognitively impaired participants

Effect sizes (95% CI)

Table 4 presents the outcomes, key findings and effect sizes of

d = −0.66 (−1.67 to

Data not available

Pre-intervention
the reviewed studies in people with cognitive impairment. Two

for calculation
outcomes, executive functions (in 4 out of 5 studies) and atten-
tion/processing speed (in 4 out of 5 studies), were commonly used
in the reviewed studies. Two studies reported significant improve-

0.34)
ments in executive functions from Frontal Assessment Battery and
Clock Drawing Test (Coelho et al., 2012) in AD and Rey-Osterrieth

Significant between-group effects

Complex Figure Test (Kounti et al., 2011) in MCI. These two stud-
ies also found significant effects on attention/processing speed
from Symbol Search Subtest of Wechsler Adult Intelligence Scale III

(compared to CG & CG*)

(Coelho et al., 2012) and Test of Everyday Attention (Kounti et al.,
2011).

(compared to CG)
Three studies included measures of Verbal Fluency for language
performance, with two studies of MCI finding significant improve-
ments (Kounti et al., 2011; Suzuki et al., 2012). Kounti et al. (2011)

0/+ at FU
+/+ at FU

+/+ at FU

+/+ at FU
and Suzuki et al. (2012) also examined general cognitive func-
tions and both found significant improvements on Mini-mental

0
0

0
+
state examination (MMSE) scores. Three studies assessed memory
performance, however only one study of MCI showed significant

Executive functions & Memory Composite Score

effects on immediate recall of Wechsler Memory Scale-Revised

Sandoz clinical assessment geriatrics SCAG

(Suzuki et al., 2012). One study of MCI also used subjective mea-
sure of functional status (Functional Rating Scale of Symptoms of

Executive functions Composite Score

Independent Living Composite Score

Cognitive Function Composite Score
Dementia) which showed significant improvement (Kounti et al.,

Episodic Memory Composite Score

2011). One study measured dual-task cost (DTC) in participants
Wechsler memory scale (WMS)
Outcome Measures of interest

with dementia and observed significant effect on DTC combined

motor-cognitive performance (Schwenk et al., 2010).

Everyday competence
BEC 96 questionnaire

Emotional Status
3.7. Methodological quality of included studies

The results of the methodological quality assessment are pre-

sented in Table 5. The reviewed studies fulfilled 7–11 quality
criteria out of the maximum of 13 items. Only one RCT (Schwenk
et al., 2010) performed a concealed randomization and was the only
Post-intervention 2

Post-intervention 4

study that had both rater and subject blinded. However, this was
Post-intervention
12 months; FU 5

the only one study that did not use intention-to-treat in data analy-
Study Characteristics and results of studies in cognitively healthy populations.

sis. Three RCT (Barnes et al., 2013; Legault et al., 2011; Suzuki et al.,
Follow-up

2012) did not state whether the random allocation was concealed,

+: positive effect for intervention group; 0: no difference between groups.

months

months

with two (Legault et al., 2011; Suzuki et al., 2012) did not report the
years

method of random sequence generation. The RCT by Legault et al.

(2011) was stated as single-blinded but did not report the party
(CT) & Physical training

(CT) & Physical training

Combined Aerobic (AT)
& Mental training (MT)

which was blinded. Two RCT (Barnes et al., 2013; Suzuki et al., 2012)
Combined Cognitive

Combined Cognitive

and one other non-RCT (Kounti et al., 2011) reported rater-blinded.

One study (Oswald et al., 2006) recruited a random sample but the
group allocation was not random.
Intervention

All the included studies reported eligibility criteria, baseline

similarity, same follow-up length, pre-specified outcomes as well
CG: control group; CG*: comparison group.
(PT)

(PT)

as point measures and measures of variability for the primary

d: standard between-group effect size.
FU: follow-up; N: number of subjects.

outcome measures. Seven of the eight studies achieved outcome

Subject

N = 375

measures from more than 85% of the participants initially allo-

N = 32

N = 73

cated to groups at least at one time point of measures. Main

methodological shortcomings or bias identified included no or
CI: confidence interval.

inadequate randomization, non-concealed allocation, lack of blind-

Oswald et al. (2006)
Legault et al. (2011)
Fabre et al. (2002)

ing and unclear reliability of outcomes measures in some studies.

All studies fulfilled the criteria for 7 or more quality items,
with one (Schwenk et al., 2010) meeting 11 out of 13 quality
criteria. Therefore, seven of the reviewed studies were consid-
Study
Table 3

ered to be of medium quality and one was assessed as high

quality.

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68
Table 4
Study characteristics and results of studies in cognitively impaired populations.

Study Subject Intervention Follow-up Outcome Measures of Interest Significant Effect sizes (95% CI)
between-group effects

Pre-intervention Post-intervention

Barnes et al. (2013) N = 126; older Combined Mental Post-intervention Rey Auditory Verbal Learning Test 0
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adults with Activity & Aerobic 12 weeks (RAVLT)

memory Exercise Verbal Fluency (letter & category) 0
complaints Digit Symbol Substitution Test 0
(DSST)
Trail Making Test (TMT) 0
Eriksen Flanker Test (EFT) 0
Useful Field of View (UFOV) 0

Coelho et al. (2012) N = 27; Alzheimer’s Multimodal Post-intervention Frontal Assessment Battery (FAB) + d = −0.35 (−1.11 to d = 1.18 (0.37–2.01)
disease (AD) Dual-task exercise 16 weeks 0.41)
Clock Drawing Test (CDT), + d = −0.14 (−0.89 to d = 0.96 (0.16–1.76)
0.62)
Symbol Search Subtest of WAIS-III + d = −0.04 (−0.79 to d = 1.57 (0.71–2.44)

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75

(Symbol) 0.72)

Kounti et al. (2011) N = 58; mild Dual-task kinetic Post-intervention Mini-mental State Examination + d = 0.40 (−0.12 to 0.92) d = 0.63 (0.11–1.16)
cognitive exercise 20 weeks (MMSE)
impairment Test of Everyday Attention (TEA) + d = 0.08 (−0.44 to 0.59) d = 0.24 (−0.28 to 0.76)
Rey Auditory Verbal Learning Test 0
(RAVLT)
Rey-Osterrieth Complex Figure + d = 0.01 (−0.50 to 0.53) d = 0.52 (0.001–1.05)
Test (ROCFT)
Verbal Fluency Test (FAS) + d = 0.38 (−0.14 to 0.90) d = 0.62 (0.09–1.14)
Functional Rating Scale of + d = 0.17 (−0.34 to 0.69) d = 0.59 (0.06–1.11)
Symptoms of Dementia (FRSSD)
Functional Cognitive Assessment 0
Scale (FUCAS)
Wisconsin Card Sorting Test 0
(WCST)
Wechsler Adult Intelligence 0
Scale-Revised (WAIS-R)
Rivermead Behavioral Memory 0
Test (RBMT)
Boston Naming Test (BNT) 0

Schwenk et al. N = 61; dementia Dual-task exercise Post-intervention DTC Cognitive performance 0 Data not available for d = 0.99 (0.39–1.59)
(2010) 12 weeks calculation
DTC Combined motor-cognitive +
performance

Suzuki et al. (2012) N = 50; amnestic Multicomponent Post-intervention 6 Mini-mental State Examination + at 6 m & 12 m d = 0.44 (−0.44–0.67) d = 0.11 (−0.45–0.66)
mild cognitive dual-task exercise months, 12 months (MMSE)
impairment Immediate recall WMS-R + at 6 m & 12 m d = 0.09 (−0.46–0.65) d = 0.16 (−0.39–0.72)
Delayed recall WMS-R 0
Digit symbol-coding (DSC) subset 0
WAIS-III
Letter verbal fluency test (LVFT) + at 12 m d = −0.16 (−0.71–0.40) d = 0.22 (−0.34–0.77)
Category verbal fluency test (CVFT) 0
Stroop Color and Word Test 0
(SCWT).

N: number of subjects; DTC: dual-task cost.

d: standard between-group effect size; CI: confidence interval.
+: positive effect for intervention group; 0: no difference between groups.
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Table 5
Overview of quality rating of reviewed studies.
Study Randomization Concealed Eligibility Baseline similarity Assessor Care provider Subject Valid reliable Same follow-up Outcome from Pre-specified Data Intention-to-treat Sum score
allocation criteria blinded blinded blinded measures length >85% subjects outcomes presentation
Barnes et al. Yes Unclear Yes Yes Yes Unclear Unclear Yes Yes No Yes Yes Yes 9
(2013) (computer (not stated) (baseline (stated) (not stated) (not stated) (reference (21% drop-off (mean (stated)
generated characteristics stated) reported) standardized
sequence) presented) changes &
confidence

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75

intervals)
Coelho et al. No No Yes Yes Unclear No Unclear Yes Yes Yes Yes Yes Yes 8
(2012) (assigned) (baseline (not stated) (not stated) (reference (number (mean & SD) (completer
characteristics stated) presented) comparison)
presented
Fabre et al. No No Yes Yes Unclear Unclear No Yes Yes Yes Yes Yes Yes 8
(2002) (randomly (baseline (not stated for (not stated) (reference (stated) (mean & (explicitly reported
assigned) characteristics outcome stated) standard error) same number of
presented) measures) subjects at pre and
post)
Kounti et al. No No Yes Yes Yes No No Yes Yes Yes Yes Yes Yes 9
(2011) (assigned) (completer baseline (stated) (data & (completer (mean & SD) (completer
comparison) reference comparison) comparison)
stated)
Legault et al. Unclear Unclear Yes Yes Unclear Unclear Unclear Unclear Yes Yes Yes Yes Yes 7
(2011) (method of random (not stated) (baseline (not stated) (not stated) (not stated) (stated (data (mean & SD; (stated)
sequence characteristics reference reported) mean change &
generation was not presented) without SE)
stated) information)
Oswald et al. No No Yes Yes No Unclear Unclear Unclear Yes Yes Yes Yes Yes 7
(2006) (stated) (stated) (baseline (stated) (not stated) (not stated) (not all stated) (completer (z-score mean & (stated)
characteristics comparison at SD; effect size d)
presented & with post-
adjustment in intervention)
analysis)
Schwenk et al. Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes No 11
(2010) (numbered (by independent (stated baseline and (stated) (stated) (reference (data (mean & SD) (completer
container) person) completer baseline stated) reported) analysis)
comparison)
Suzuki et al. Unclear Unclear Yes Yes Yes No No Yes Yes Yes Yes Yes Yes 9
(2012) (method of random (not stated) (baseline (stated) (reference (data (group mean (stated)
sequence characteristics stated) reported) difference &
generation was not presented) confidence
stated) intervals)

69
 70 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75
Overall, the results of the reviewed studies in both populations
with and without cognitive impairment were conflicting. Among
the three studies with cognitively healthy participants, one study
found no effects while two studies revealed significant effects.
Fabre et al. (2002) reported a significant effect on memory perfor-
mance (d = 1.29). Oswald et al. (2006) found significant effects, with
within-group effect sizes reported, on general cognitive functions
(d+ = 1.14), subjective rating of cognitive impairment (d+ = 0.59)
and functional status (d+ = 0.27), which were sustained at 5-years
follow-up.
Among the five studies with cognitively impaired participants,
one study found no effect while four studies reported significant
improvements in outcomes including cognitive-motor dual-task
cost (d = 0.99) in dementia; executive functions (d = 0.52–1.18) and
attention (d = 0.24–1.57) in MCI and AD; general cognitive func-
tions (d = 0.11–0.63), language (d = 0.22–0.62), memory (d = 0.16)
and subjective rating of functional status (d = 0.59) in MCI.
4. Discussion
This systematic review examined the efficacy of combined cog-
nitive and exercise training to improve cognitive functions in older
adults with and without cognitive impairment. Eight studies were
identified in this review, five of which included a population with
cognitive impairment and three studies included a population
without cognitive impairment. The paucity of research in this area
was obvious, particularly among the wide progressively degenerat-
ing cognitive continuum in populations with cognitive impairment
(Petersen, 2004). The studies were published within the past 10
years (2002–2013). This suggests that research to assess the impact
of combined cognitive and physical exercise on cognitive functions
in older adults is still in its fledgling stage. The identified studies
were from a variety of mainly developed countries. The potential
benefits of a combined intervention appears to be attracting the
interest of researchers throughout the world however more stud-
ies are needed before generalization of reliable evidence can be
reached, especially in developing countries.
The results of this review showed that combined cognitive
and exercise training can be effective for improving the cognitive
functions and functional status of older adults with and without
cognitive impairment. Significant improvements were found in two
out of the three studies with cognitively healthy populations and
in four out the five studies with cognitively impaired populations.
The limited number and heterogeneity of the reviewed studies do
not enable any firm conclusion to be drawn. Nevertheless, specific
study characteristics can be identified in this review that may help
to promote intervention fidelity in future studies.
4.1. Comparison and control group design
Appropriate design of the comparison and control groups is
important to allow critical investigation on the comparative effec-
tiveness between the specific components of an intervention and
other components or common conditions being studied (Hart et al.,
2008; Kinser and Robins, 2013).
In cognitively healthy populations, Fabre et al. (2002) found
the combined training demonstrated significant improvement in
memory compared to either single memory or aerobic training
alone. Oswald et al. (2006) showed the combined cognitive and
physical training improved general cognitive performance and sub-
jective measures of functional status compared to a no treatment
control, and proved more promising than the single training groups.
The multi-arm comparison group design in these studies allow
a clear comparison between the unique component in the com-
bined intervention and the common components (single cognitive
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or exercise training) in the comparison groups as well as the non-
specific components (staff exposure or social contact) in the control
group. This design can greatly strengthen the validity and credi-
bility of the findings in the studies. Nevertheless, the exposure to
interventions varied between the combined and single interven-
tions.
In a population with cognitive complaint, Barnes et al. (2013)
also used a multi-arm comparison group design and the inter-
vention time were the same among all the intervention and
comparison groups. However, no significant differences were
observed between the intervention and the comparison groups.
The authors believed that both the active-control activities and the
placebo-control activities may be beneficial to the participants and
have potential impact on the outcomes. Therefore, a larger sam-
ple size would be required to have adequate power for detecting
significant group differences (Baskin et al., 2003; Hart et al., 2008).
All the other four studies with cognitively impaired popula-
tions that used a dual-task exercise group compared with a control
group reported significant findings. It can be challenged that the
improvements observed in the studies may not be attributed to
the interventions or, more precisely, the specific component of
the intervention. The use of a no-treatment group by Coelho et al.
(2012) may control for the effects of time and the effects of repeated
testing on outcome measures. The use of a waitlist group by Kounti
et al. (2011) may also control for the effects from an expectancy of
improvement. The use of health education by Suzuki et al. (2012)
may further control for other non-specific treatment effects (e.g.
social contact) but the three sessions’ contact time was far less than
the 120 h intervention time, which may lead to ineffective control
of the non-specific moderators by the control group (Hart et al.,
2008; Safer and Hugo, 2006). Schwenk et al. (2010) compared the
intervention group with a low intensity exercise group. This may
allow for a further comparison on the effects from the difference
in exercise intensity. Studies have found that moderate intensity
aerobic exercise is more effective for improving cognitive function
than low intensity exercise (Colcombe and Kramer, 2003), whereas
combined aerobic and strength training has a greater effect com-
pared to single mode exercise training (Erickson and Kramer, 2009).
A good comparison control should omit the unique intervention
component under investigation, while possessing the common
ingredients in equal measure (Safer and Hugo, 2006). Although pos-
itive findings were reported in all the four studies used dual-task
training as intervention, it can still be questionable whether the
improvements were all attributed to the dual-task components. An
appropriate comparison with the potential beneficial components
or moderators is important to validate the differential effects under
the investigation. As a result, appropriate activity selection in com-
parison control and a well-designed comparison group is crucial in
future studies on the efficacy of combined interventions.
4.2. Study population screening
Cognitive impairment/dementia may be caused by multiple
intertwined pathological factors (Stewart, 2002). Neurodegen-
erative conditions such as AD and cerebrovascular disease,
including subclinical brain injury, silent brain infarction, and clin-
ically overt stroke, are the most common causes of cognitive
impairment/dementias in older individuals (Alzheimer’s Disease
International 2009; Gorelick et al., 2011). Vascular dementia (VaD)
is the second most common form of dementia after AD, accounting
for 20–30% of the diseased population (Stewart, 2002). Importantly,
there is increasing evidence that vascular pathology frequently
co-exists with neurodegenerative pathology and most demen-
tias have both vascular and neurodegenerative features (Dichgans
and Zietemann, 2012; Neuropathology Group, 2001). More than
30% of AD population has been found to have cerebrovascular
 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75
pathology (Roman, 1999). The pathogenic importance of vascular
contributions in cognitive impairment and dementia merits partic-
ular attention in diagnosis and screening for study populations.
Among the reviewed studies in populations with cognitive
impairment, Suzuki et al. (2012) used the criteria by Petersen
et al. (2001) for diagnosis of aMCI population. Kounti et al. (2011)
used the criteria of Petersen et al. (2001) and Artero et al. (2006)
for multi-domain MCI and the National Institute of Neurologi-
cal and Communicative Disorders and Stroke-Alzheimer’s Disease
and Related Disorder Association (NINCDS-ADRDA) for dementia
(McKanhnn et al., 1984). Both of these studies performed neu-
roimaging examination, in addition to neuropsychological tests and
medical history, to confirm a diagnosis and reported exclusion of
persons with stroke. No information was reported on the patho-
logical nature of cognitive impairment in the population selected.
Coelho et al. (2012) did not report on the diagnostic details for the
population selection, but used the Diagnostic and Statistical Man-
ual of Mental Disorders 4th edition (DSM-IV) criteria (American
Psychiaric Association, 2000) for diagnosis of Alzheimer’s disease,
which also excluded those with cognitive deficits due to cere-
brovascular disease. Barnes et al. (2013) also excluded those with
other neurological conditions in their study with a cognitive com-
plaint populations. The diagnosis was based on interview, physician
diagnosis and neuropsychological assessment. Indeed, cerebrovas-
cular pathologies, such as stroke, have been found to be typically
associated with VaD (De la Torre, 2002). Studies have shown that
cerebral infarcts (covert or overt) are additive with Alzheimer’s dis-
ease pathology in that cerebral ischemia worsens the effects of AD
on cognitions (Esiri et al., 1999; Zekry et al., 2002).
Only one study (Schwenk et al., 2010) considered the vascular
nature of dementia by including the criteria for the diagnosis of
dementia and VaD, based on both the NINCDS-ADRDA (McKanhnn
et al., 1984) and the National Institute of Neurological Disor-
ders and Stroke-Association International pour la Recherche en
l’ Enseignement en Neurosciences (NINCDS-AIREN; Roman et al.,
1993). However, the authors did not report on any neuropatho-
logy evaluations or methods for operationalization of the screening
criteria. Silent infarct also has been found to influence cognition
even in normal aging (Vermeer et al., 2003). Nevertheless, in the
reviewed studies with cognitively healthy population, no studies
addressed or investigated the potential impact of silent vascular
contribution to cognition in normal persons.
Studies have shown that the presence of vascular lesions con-
tributes to the severity of cognitive impairment (Snowden et al.,
1997; Riekse et al., 2004; Petrovitch et al., 2005). Different sub-
groups may have different cognitive deficits and responses to
treatments associated with the differences in etiologies (Gorelick
et al., 2011; Moorhouse and Rockwood, 2008). Identifying the
causes of cognitive impairment/dementia is of particular impor-
tance in the investigation for effective preventative and treatment
strategies (Stephen et al., 2009). Clear identification and report on
the specific nature of the study population selected (neurodegen-
erative, vascular, mixed pathology) will be crucial to facilitate cross
study comparison and generalization of study findings.
4.3. Training sequence in combined intervention
The sequence in delivering the cognitive training and exer-
cise training sessions on combined training may have a potential
impact on the intervention outcomes. Legault et al. (2011) found
no intervention effects when the physical training was delivered
after the cognitive training. Oswald et al. (2006) however found
positive intervention effects with the physical training sessions
delivered before the cognitive training for half of the intervention
period. Animal studies found that exercise promotes neurogene-
sis in the brain and improves learning (Farmer et al., 2004; van
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71
Praag et al., 2005). Neuroimaging studies in populations with cog-
nitive impairment reported that compensatory recruitment of new
brain areas were observed during the performance of a demanding
task (Reuter-Lorenz and Lustig, 2005; Belleville et al., 2011). Fabel
et al. (2009) proposed that the exercise in combined training pre-
pares the potential of the brain for increased neurogenesis upon
additional exposure to cognitive enrichment. In a recent animal
study on the effects of combined training with positive findings,
the physical activity was set to precede the cognitive training or
the participants were re-exposed to cognitive training after physi-
cal training (Langdon and Corbett, 2012). It appears more favorable
to have the exercise sessions delivered before the cognitive training
session, in order to better prepare the brain for the compensatory
recruitment process in the subsequent cognitive training sessions.
Nevertheless, more intervention studies are needed to systemati-
cally reveal the potential impacts of training sequence on training
outcomes.
4.4. Dual-task component
The high quality RCT by Schwenk et al. (2010) found significant
improvement in dual-task performance only under complex dual
task conditions. The patients needed to be adequately challenged
to reach the effects. It was reported that higher basic DTC were
associated with a higher percentage of improvement in DTC. This
highlights the importance of adjusting the level of the training tasks
to meet individual capacity in intervention design, thus making
optimal use of an individual’s latent potential (Hertzog et al., 2009).
Although the findings from using dual-task intervention are
encouraging, the results need to be interpreted with caution. It has
been challenged that the similarity of the dual-tasks assigned in
the interventions and the assessment tasks may produce a learn-
ing effect ultimately affecting the reliability of the outcome results
(Pichierri et al., 2011). Therefore, selection of alternative dual-tasks
should be considered in future studies using dual-task exercise.
4.5. Intervention period
Suzuki et al. (2012) reported significant group effects on gen-
eral cognitive function and memory at 6 months which were
not demonstrated in the MCI population at 12 months treatment
end. The intervention period in the study of Suzuki et al. (2012)
was the longest compared to that in other studies (3–5 months)
with cognitively impaired participants. A previous meta-analysis
has found negative association between the training duration and
the cognitive intervention effect on persons with MCI and sug-
gested that studies with longer sessions and longer duration of
total sessions would produce smaller effect sizes (Li et al., 2011).
As revealed by the study results in this review, an intervention
period of three to six months has shown to be more favorable
than a longer intervention period in populations with cognitive
impairment. Nevertheless, the moderating effect of program dura-
tion for cognitively impaired populations may need to be examined
in future studies.
4.6. Outcome measure selection
The studies by Suzuki et al. (2012) in amnestic MCI and Barnes
et al. (2013) in participants with memory complaints did not find
any effects on executive functions. In contrast, the studies by Coelho
et al. (2012) in AD participants and Kounti et al. (2011) in MCI par-
ticipants found significant improvements in executive functions
and attention. Impairments in executive functions have been found
in people with cognitive complaint (Rouch et al., 2008), amnestic
and non-amnestic MCI (Reinvang et al., 2012) and AD (McGuinness
et al., 2010). Executive function deficits have consistently been
 72 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75
found to predict AD conversion (Ritchie et al., 2001; Tabert et al.,
2006) although it remains unclear how executive functions are
impaired in amnestic MCI (Bisiacchi et al., 2008; Marshall et al.,
2011). Therefore, it is important to include executive functions
as one of the intervention outcomes in studies with cognitively
impaired populations. Nevertheless, the changes in executive func-
tions could be so subtle that some of the widely used executive
function tests may not be sensitive enough to detect the mini-
mal changes (Espinosa et al., 2009; Pickens et al., 2010). Moreover,
the diversity of components under the umbrella of executive func-
tions (Miyake et al., 2000) may further complicate the difficulty in
assessing executive functions. The approach to use multiple out-
come measures, as that in the study by Kounti et al. (2011), may be
helpful but care must be taken to balance the assessment burden
on the participants (Pickens et al., 2010). The selection of outcome
measures with appropriate sensitivity and specificity to the study
population should be of primary concern in future studies (Karrasch
et al., 2005; Parra et al., 2012).
4.7. Visual-spatial component
Kounti et al. (2011) was the only study that used dual tasks with
visual-spatial stimuli. Studies have found that both MCI and AD
patients show deficits in visual spatial function (Iachini et al., 2009;
Possin, 2010) which is also one of the predictors of conversion to
dementia of persons with MCI (Amieva et al., 2004; Griffith et al.,
2006). Indeed, visual spatial function is a very important cognition
in everyday functioning, for instance, navigating a car safely in driv-
ing or searching the routes in a new environment. Subtle declines
in this ability would impose a great impact on everyday livings in
elderly populations (Alescio-Lautier et al., 2007; Iachini et al., 2009;
Possin, 2010). Studies have found that visual spatial ability can be
trained through practice (Jaeggi et al., 2008; Wright et al., 2008).
Therefore, including visual spatial components in interventions as
well as in outcome measures are highly recommended in future
studies.
4.8. Generalization of training effects
Training effects can reflect real benefits and practical values of
an intervention only if the results of the intervention can be gen-
eralized to other non-trained tasks, settings and sustained over
time (Boelen et al., 2011; Glasgow et al., 2003). Previous cogni-
tive training studies have shown improvements in training-related
outcomes but limited generalization to non-trained tasks (Noack
et al., 2009; Simon et al., 2012). The generalizability of the inter-
vention results to everyday functioning is regarded as an important
implication of success (Glasgow et al., 2003; Lambert et al., 2010).
In the reviewed studies with a cognitively healthy populations,
Legault et al. (2011) assessed the impact of combined training
on non-trained cognitive domain (executive function) but found
no significant effects. Oswald et al. (2006) reported positive gen-
eralization of the intervention effects in functional status and
emotional status, which was also sustained over time at 5-year
follow up. However, the assessment tools involved were non-
standardized subjective ratings.
In populations with cognitive impairment, all of the five
reviewed studies used neuropsychological assessments to assess
training-related cognitive domains including attention, language
and executive functions. Only Kounti et al. (2011) also included
the Functional Rating Scale of Symptoms of Dementia (FRSSD)
and the Functional Cognitive Assessment Scale (FUCAS) to assess
functional status, and found positive post-intervention effects for
FRSSD, which is an informant-report rating. Nevertheless, tradi-
tional psychometric tests have been challenged for not being able
to adequately reflect older adults’ functioning in a real everyday
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context where the demands may be different to that in a test
environment (Law et al., 2012; Marsiske and Willis, 1995). More
ecologically validated tests should be included to examine the prac-
tical translation of intervention effects.
The ability to maintain independent living in the community
is of particular importance for most elderly adults (Mack et al.,
1997). Studies have shown that persons with cognitive impairment
have difficulties in daily functioning, especially in complex every-
day tasks that rely heavily on memory and reasoning (Aretouli
and Brandt, 2010; Pérés et al., 2006). This imposes a potential
impact on the safety and quality of life of the person with cogni-
tive impairment (Gauthier et al., 2006; World Health Organization
and Alzheimer’s Disease International, 2012). It will be of utmost
importance for future intervention studies to include ecological
tests and investigate the generalizability of training effects to real
world functional outcomes.
Overall, more well-designed studies, with special attention to
comparison control and population screening, outcome selection,
training sequence, intervention period and generalizability of out-
comes, are still needed to reveal the differential effects of combined
cognitive and exercise training especially in older population with
cognitive impairments. In the absence of a cure for cognitive
impairment or dementia, further research efforts are needed to
explore the potential benefits of this new intervention paradigm
to help delay, and possibly reverse the progression of cognitive
impairment.
4.9. Limitations
Limitations of this review should be noted. The limited num-
ber and heterogeneity of the reviewed studies did not allow critical
analysis of the results for different groups of populations with cog-
nitive impairment. Further, the search terms were limited to title,
abstract and keywords to constrain the magnitude of the search
yield to a manageable size and only citations published in English
were included in this review. These restrictions may limit cover-
age of all potential studies under this topic. Moreover, initial study
screening with title and abstract may lead to further limited cover
of possible intervention identification although full text would be
drawn for examination whenever a decision could not be judged
by screening with title and abstract.
5. Conclusion
Results of the present review showed that studies with
cognitively healthy populations revealed significant benefits of
combined cognitive and exercise interventions on general cogni-
tive functions, memory and functional status compared to active
control groups. Studies with cognitively impaired populations also
showed significant improvements in general cognitive functions,
memory, executive functions, attention and functional status in
persons with MCI and AD or dementia, but lack comparison with
active control groups.
In conclusion, combined cognitive and exercise training can
be effective for improving the cognitive functions and functional
status of older adults with and without cognitive impairment. How-
ever, limited evidence can be found in populations with cognitive
impairment when the evaluation includes an active control group
comparison. More well-designed studies are required before one
can draw any firm conclusion on the efficacy of the combined cog-
nitive and exercise intervention in older adults.
Conflicts of interest
We declare that there are no conflicts of interest.
 L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 61–75
Source of funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.arr.2014.02.008.
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