Effects of Combined Cognitive and Exercise Interventions On Cognition in Older Adults With and Without Cognitive Impairment - A Systematic Review

Ageing Research Reviews 15 (2014) 6175
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
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
b
a r t i c l e
i n f o
Article history:
Received 5 November 2013
Received in revised form 25 February 2014
Accepted 28 February 2014
Available online 12 March 2014
Keywords:
Systematic review
Cognitive impairment
Healthy older adults
Combined intervention
Dual-task exercise
a b s t r a c t
Global concern on the potential impact of dementia is mounting. There are emerging calls for studies in
older populations to investigate the potential benets of combining cognitive and exercise interventions
for cognitive functions. The purpose of this systematic review is to examine the efcacy of combined
cognitive and exercise training in older adults with or without cognitive impairment and evaluate the
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
list from the included papers and additional internet searches were also done. Eight studies were identied in this review, ve of which included a cognitively impaired population and three studies included
a cognitively healthy population. The results 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. 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 benets of this new intervention paradigm.
2014 Elsevier B.V. All rights reserved.
Contents
1.
2.
3.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Search strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
Inclusion/exclusion criteria and selection process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.
Data extraction and analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.
Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.
Study characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.
Participants and settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.1.
Studies with cognitively healthy participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.2.
Studies with cognitively impaired participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4.
Intervention duration and group comparison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4.1.
3.4.2.
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Corresponding author at: Occupational Therapy Discipline, James Cook Drive, Douglas; School of Public Health, Tropical Medicine and Rehabilitation Sciences, Rehabilitation 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), ona.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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L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175
Intervention programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5.1.
3.5.2.
3.6.
Outcome measures and intervention effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6.1.
3.6.2.
3.7.
Methodological quality of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Comparison and control group design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.
Study population screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
Training sequence in combined intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4.
Dual-task component . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.5.
Intervention period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.6.
Outcome measure selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.7.
Visual-spatial component . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.8.
Generalization of training effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.9.
Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Source of funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.5.
4.
5.
1. Introduction
The increasing prevalence of cognitive impairment with age
intensies the potential impact upon global health and health care.
It has been projected that there will be 7.7 million new cases
of dementia each year, implying a new case of dementia every
4 s (WHO and ADI, 2012). The World Health Organization (WHO)
has urged global efforts to take a serious focus on the potential
impacts of dementia on the societal and health care systems worldwide. Individuals with mild cognitive impairment (MCI) are at high
risk of progressing to Alzheimers diseases and other dementias,
with reported conversion rate of 50% in 23 year (Amieva et al.,
2004) and even up to 60100% in 510 years (Morris et al., 2001;
Petersen, 2004). Addressing the lack of pharmacological treatment for individuals with MCI (Alzheimers Association, 2013), it
is critical to explore the potential effects of non-pharmacological
interventions.
The benets of exercise on cognition are widely recognized
(Cotman and Berchtold, 2007; Kramer and Erickson, 2007; van
Praag, 2009). Animal studies have consistently shown exercise increases cell proliferation and neurogenesis in the dentate
gyrus of the hippocampus (Fabel et al., 2003; Kronenberg et
al., 2006), an important brain area for learning and memory.
Exercise regulates a number of growth factors such as brainderived neurotrophic factor (BDNF), which plays a crucial role
in neuroprotection and synaptic plasticity (Adlard et al., 2005;
Vaynman et al., 2004); insulin-like growth factor 1 (IGF-1), which
promotes neuronal growth and improves cognitive performance
(Cotman and Berchtold, 2002; Liorens-Martin et al., 2010); vascular
endothelial growth factor (VEGF), which stimulates angiogenesis and vasculogenesis (Tang et al., 2010; Zhang et al., 2013)
and promotes brain ischemic tolerance (Zhang et al., 2011). Furthermore, exercise reduces inammatory cytokines and oxidative
stress, which suggests anti-inammatory and antioxidant effects
on the brain (Pervaiz and Hoffman-Goetz, 2011; Santin et al.,
2011).
Colcombe et al. (2006) also found that exercise correlates with
an increase in brain volume over the frontal, parietal, and temporal cortices in humans. Studies also have shown that exercise
can promote cerebral blood ow which enhances neurogenesis
and improves learning (Farmer et al., 2004; van Praag et al., 2005),
as well as promotes cardiovascular tness and therefore reduces
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peripheral risk factors (e.g. hypertension) for cognitive decline

(Cotman et al., 2007; Pereira et al., 2007).
Whilst the uniqueness of exercise-induced effects to enhance
brain health and cognitive functions through multiple routes is
evident, results of intervention studies on single exercise intervention are disappointing (Busse et al., 2009; Etnier et al., 2006). A
recent systematic review showed that strong evidence to support
the effects of exercise interventions on cognitive functions of older
adults is still lacking (Snowden et al., 2011).
It has been proposed that exercise has to occur in the context
of a cognitively challenged environment in order to be effective for
inducing neural and cognitive benets rather than exercise alone
(Fabel and Kempermann, 2008; Fabel et al., 2009). Studies also
have found that a combination of exercise and an enriched environment induces more new neurons and benets the brain greater
than either exercise or an enriched environment alone (Fabel and
Kempermann, 2008; Fabel et al., 2009; Olson et al., 2006). An animal study reported signicant improvements in cognitive ability
when combined physical and cognitive training was undertaken
(Langdon and Corbett, 2012). A combination of exercise and cognitive interventions, either sequentially or simultaneously, appears
to have the potential effect to maintain or improve cognitive functions (Langdon and Corbett, 2012; Schaefer and Schumacher, 2011).
Indeed, there are emerging calls for studies in older populations
to investigate the potential benets of combined cognitive and
physical interventions to accomplish an optimal outcome (Amoyal
and Fallon, 2012; Kraft, 2012; Rebok, 2008; Thom and Clare,
2011).
The aims of this review were: (1) to assess the efcacy of
combined cognitive and exercise training to improve cognitive
functions in older adults with and without cognitive impairment;
(2) to examine the methodological quality of the included studies;
and (3) to summarize the latest results on combined cognitive and
exercise training in older adults with or without cognitive impairment.
For the purpose of this review, combined cognitive and exercise
interventions are structured interventions that combine cognitive
training and exercise, either conducted in sequence or simultaneously under dual-tasking paradigms. Cognitive training are dened
as structure repeated practice on tasks with an inherent problem,
using standardized tasks targeting specic cognitive domains
and/or teaching strategies and skills in order to optimize cognition
63
and functioning (Clare and Woods, 2003; Martin et al., 2006).

Exercise is dened as a form of physical activity that is planned,
structured and repetitive over an extended period of time, with
the purpose to improve tness, performance or health (Casperson
et al., 1985).
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-andstandard-deviations.html). Effect sizes were interpreted as small,
d = 0.20; medium, d = 0.50; or large, d = 0.80 (Cohen, 1988).
2. Methods
2.4. Quality assessment
2.1. Search strategies
Methodological quality of the included studies was independently assessed by 2 reviewers (LL and FB) using a 13-item checklist
modied from the Delphi list (Verhagen et al., 1998), the Physiotherapy Evidence Database (PEDro) scale (Maher et al., 2003) and
the Design-specic criteria to assess for risk of bias by the Agency
for Healthcare Research and Quality (AHRQ) (Viswanathan et al.,
2012). Any disagreements identied between the two reviewers
were resolved by a third reviewer (MY) as a nal 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 quality 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 dened as: (1) High quality when presenting a
positive score on 10 or more items; (2) Medium quality when presenting a positive score on 79 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).
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 conducted 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 reviewers 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 population: older adults (aged 60 and older) with or without cognitive
impairment/decline or dementia but no mental or neurological disorders 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 without adequate specication 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 component 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 ndings. However, Cohens 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 deviations 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% condence intervals (CIs) were also
3. Results
3.1. Study selection
A summary of the selection process is illustrated in Fig. 1. The
initial database search identied 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 following: 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 identied three more articles. A total of 19 articles
were nally 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; ODwyer 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 rst 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 nonRCTs) included a population of cognitively healthy older adults
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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 modied 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 cognitively 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 combined 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 training, single cognitive training, single psycho-educational training,
single physical training and no treatment control groups (Oswald
et al., 2006).
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), Alzheimers disease (AD; Coelho et al., 2012) and mild cognitive 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 function 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 identied study which included a population with cognitive complaints
(Barnes et al., 2013) was reported under the studies with cognitively impaired population. Tables 1 and 2
illustrate the intervention characteristics of the reviewed studies 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
The number of cognitively healthy people (total 480) in the studies 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 performed cognitive screening using the modied Mini-mental Status
Examination (modied MMSE) at baseline (Legault et al., 2011).
One study was conducted in France, one in Germany and one in
United States.

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
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 walking 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 exibility training (Oswald et al., 2006).
Of the ve 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 homebased computer cognitive training plus a supervised center-based
65
Table 1
Intervention characteristics of studies in cognitively healthy populations.
Study
Design
Participants
Interventions
Total intervention
hours (h)
Control/comparison (total
hours)
Fabre et al. (2002)
Non-RCT
N = 32; France
IG/CG/CG*1/CG*2: 8/8/8/8
Supervised group
Combined Aerobic (AT) & Mental
training (MT)
? Sequence
38 h
CG: No training, but meeting

for leisure activities
CG*1: Aerobic training (AT)
CG*2: Mental training (MT)
AT: brisk walking and/or jogging

(intensity determined by
ventilation threshold
2/week for 60 min/session for 2
months
16 h
MT: eight themes: perceptive

activities, attention, intellectual
structuration, association and
imagination, language, spatial
marks, temporal marks and
associated recruiting.
1/week; 90 min/session for 2
months
12 h
Mean age (years):

IG/CG1/CG*1/CG*2:
61.9/65.7/65.4/67.5
MMSE score: not conducted
Legault et al. (2011)
RCT
N = 73; United States

IG/CG/CG*1/CG*2: 19/18/18/18
Mean age (years):

IG/CG/CG*1/CG*2:
76.9/75.4/76.0/77.5
Modied MMSE:
IG/CG/CG*1/CG*2:
94.6/94.3/95.6/94.6
Oswald et al.
(2006)
Non-RCT
N = 375; Germany
IG/CG/CG*1/CG*2/CG*3/CG*4:
32/103/57/32/115/36
Mean age (years): 79.5
Supervised group
Combined Cognitive (CT) &
Physical training (PT);
PT followed CT on the same day.
CT: Computer-based memory
training;
24 sessions (2/week, for 2
months + 1/week for 2 months);
4050 min/session
PT: aerobic & exibility training
(walking/stationary cycling)
32 center-based sessions (2/week
for 4 months); 60 min/session; plus
150 min/week home-base walking
sessions for the rst month
Supervised group
Combined Cognitive (CT) &
Physical training (PT)
PT was carried out before CT or Psy
T in a part of the training groups
and following CT or Psy T in
another part of the groups
CT: Visual search tasks;
verbal/visual memory tasks;
memory strategies
30 sessions (1/week over 1 year);
90 min/session
62 h
CG: Health education;

1/week
CG*1: Cognitive training (CT)
20 h
42 h
67.5 h
45 h
CG: No treatment
CG*1: Cognitive training (CT)
CG*2: Physical training (PT)
CG*3: Psychoeducational
training (Psy T; 45 h)
psychoeducation, group
discussion, role playing
CG*4: Combined Psy T + PT
(67.5 h)
MMSE score: Not conducted

PT: Balance, perceptual, motor
coordination exibility; gymnastic
exercises and games
30 sessions (1/week over 1 year);
45 min/session
22.5 h
IG: intervention group; CG: control group; CG*: comparison group.

MMSE: Mini-mental State Examination
exercise training (Barnes et al., 2013). Regarding the exercise components, 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

Table 3 presents the outcomes, key ndings and effect sizes of
the reviewed studies in cognitively healthy persons. Two studies
measured general cognitive functions, with one study reporting
signicant improvement in the cognitive function composite score,
and sustained at ve-year follow-up (Oswald et al., 2006). Two
studies assessed memory performance, with one study showing
a signicant 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 signicant improvements in cognitive
66
Table 2
Intervention characteristics of studies in cognitively impaired populations.
Study
Barnes et al. (2013)
Kounti et al. (2011)
Schwenk et al. (2010)
Suzuki et al. (2012)
RCT (Rater-blind)
Participants
Interventions
N = 126; older adults with memory

complaints; USA
IG/CG/CG*1/CG*2: 32/31/31/32
Mean age: 73.4 years
Modied MMSE:
IG/CG/CG*1/CG*2: 94.0/94.4/94.6/94.8
Independent Home-based + center-based

supervised class
Combined Mental Activity (MA-I) & Aerobic
Exercise (Ex-I)
MA-I: independent computer-based training at
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
N = 27; Alzheimers disease (AD); Brazil

IG/CG: n = 14/13
Mean age (years):
IG/CG: 78.0/77.1
MMSE score:
IG/CG: 19.5 4.1/19.0 2.9
Supervised group
Multimodal Dual-task exercise:
Strength/resistance training, moderate
intensity aerobic capacity/balance training,
motor activities (bouncing ball, walking,
exercise with weights); plus simultaneous
cognitive tasks (naming/words generation or
reacting to verbal command)
16 weeks; 3/week; 60 min/session
Non-RCT
(Rater-blinded)
N = 58; mild cognitive impairment; Greece

IG/CG: 29/29
Mean age (years):
IG/CG: 70.48/67.83
MMSE score:
IG/CG: 28.03 1.61/27.34 1.83
Supervised group
Dual-task kinetic exercise:
visual-active movement, visual-walking,
visual-balance, visual-ne motor,
auditory-free movement
20 sessions, 1/week; 90 min/session
RCT
Double-blinded
(Rater & subject
blinded)
N = 61; dementia; Germany

IG/CG: 26/35
Mean age (years):
IG/CG: 80.4/82.3
MMSE score:
IG/CG: 21.0 2.9/21.7 2.9
Supervised group
Dual-task exercise
Progressive resistance and functional balance
training; then progress to specic dual-task
training (e.g. walking while throwing
ball/calculation; 1015 min individual)
12 weeks; 2/week; 120 min/session
RCT (Rater-blind)
N = 50; amnestic mild cognitive

impairment; Japan
IG/CG: 25/25
Mean age: 76 7.1 years;
MMSE score:
IG/CG: 26.8 1.8/26.6 1.6
Supervised group
Multicomponent dual-task exercise:
Moderate intensity aerobic exercise, muscle
strength, postural balance & dual task training;
plus self-monitoring daily home-based
exercise (outdoor walking)
80 sessions over 12 months; 2/week;
90 min/session
Non-RCT
IG: intervention group; CG: control group; CG*: comparison group.

MMSE: Mini-mental State Examination.
Total intervention hours (h)
72 h
36 h
36 h
Control/comparison (total hours)

CG: Mental activity (MA-I) &
Exercise control (EX-C;
stretching, toning) (72 h)
CG*1: Aerobic exercise (EX-I) &
Mental activity control (MA-C;
DVD educational lecture) (72 h)
CG*2: Exercise control (EX-C) &
Mental activity control (MA-C)
(72 h)
CG: No intervention
48 h
CG: Wait-list control

30 h
48 h
120 h
CG: Motor placebo group: low

intensity exercise including
exibility exercise,
calisthenics, and ball games
while sitting (24 h)
Health education; 3 sessions

over 12 months
Coelho et al. (2012)
Design
Data not available

for calculation
N = 375
CG: control group; CG*: comparison group.

FU: follow-up; N: number of subjects.
+: positive effect for intervention group; 0: no difference between groups.
CI: condence interval.
d: standard between-group effect size.
Cognitive Function Composite Score

Sandoz clinical assessment geriatrics SCAG
Independent Living Composite Score
Everyday competence
Emotional Status
+/+ at FU
0/+ at FU
+/+ at FU
0
+/+ at FU
Data not available

for calculation
(compared to CG)
Post-intervention
12 months; FU 5
years
0
0
Executive functions Composite Score
Episodic Memory Composite Score
Oswald et al. (2006)
Combined Cognitive
(CT) & Physical training
(PT)
0
Executive functions & Memory Composite Score
Post-intervention 4
months
N = 73
Legault et al. (2011)
Combined Cognitive
(CT) & Physical training
(PT)
d = 1.29 (0.212.36)
BEC 96 questionnaire
Wechsler memory scale (WMS)
0
+
Post-intervention
d = 0.66 (1.67 to
0.34)
Post-intervention 2
months
N = 32
Fabre et al. (2002)
Combined Aerobic (AT)

& Mental training (MT)
Subject
Intervention
67
Study
The results of the methodological quality assessment are presented in Table 5. The reviewed studies fullled 711 quality
criteria out of the maximum of 13 items. Only one RCT (Schwenk
et al., 2010) performed a concealed randomization and was the only
study that had both rater and subject blinded. However, this was
the only one study that did not use intention-to-treat in data analysis. Three RCT (Barnes et al., 2013; Legault et al., 2011; Suzuki et al.,
2012) did not state whether the random allocation was concealed,
with two (Legault et al., 2011; Suzuki et al., 2012) did not report the
method of random sequence generation. The RCT by Legault et al.
(2011) was stated as single-blinded but did not report the party
which was blinded. Two RCT (Barnes et al., 2013; Suzuki et al., 2012)
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.
All the included studies reported eligibility criteria, baseline
similarity, same follow-up length, pre-specied outcomes as well
as point measures and measures of variability for the primary
outcome measures. Seven of the eight studies achieved outcome
measures from more than 85% of the participants initially allocated to groups at least at one time point of measures. Main
methodological shortcomings or bias identied included no or
inadequate randomization, non-concealed allocation, lack of blinding and unclear reliability of outcomes measures in some studies.
All studies fullled 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 considered to be of medium quality and one was assessed as high
quality.
Table 3
Study Characteristics and results of studies in cognitively healthy populations.
3.7. Methodological quality of included studies
Follow-up
Outcome Measures of interest
Signicant between-group effects
Effect sizes (95% CI)

Table 4 presents the outcomes, key ndings and effect sizes of
the reviewed studies in people with cognitive impairment. Two
outcomes, executive functions (in 4 out of 5 studies) and attention/processing speed (in 4 out of 5 studies), were commonly used
in the reviewed studies. Two studies reported signicant improvements in executive functions from Frontal Assessment Battery and
Clock Drawing Test (Coelho et al., 2012) in AD and Rey-Osterrieth
Complex Figure Test (Kounti et al., 2011) in MCI. These two studies also found signicant effects on attention/processing speed
from Symbol Search Subtest of Wechsler Adult Intelligence Scale III
(Coelho et al., 2012) and Test of Everyday Attention (Kounti et al.,
2011).
Three studies included measures of Verbal Fluency for language
performance, with two studies of MCI nding signicant improvements (Kounti et al., 2011; Suzuki et al., 2012). Kounti et al. (2011)
and Suzuki et al. (2012) also examined general cognitive functions and both found signicant improvements on Mini-mental
state examination (MMSE) scores. Three studies assessed memory
performance, however only one study of MCI showed signicant
effects on immediate recall of Wechsler Memory Scale-Revised
(Suzuki et al., 2012). One study of MCI also used subjective measure of functional status (Functional Rating Scale of Symptoms of
Dementia) which showed signicant improvement (Kounti et al.,
2011). One study measured dual-task cost (DTC) in participants
with dementia and observed signicant effect on DTC combined
motor-cognitive performance (Schwenk et al., 2010).
(compared to CG & CG*)
impairment (Sandoz clinical assessment geriatrics) at follow-up as

well as in functional status (Independent living composite score)
at post-intervention and at ve-year follow-up. Only one study
assessed executive functions but found no effects (Legault et al.,
2011).
Pre-intervention
68
Table 4
Study characteristics and results of studies in cognitively impaired populations.
Study
Barnes et al. (2013)
Coelho et al. (2012)
Schwenk et al.
(2010)
Suzuki et al. (2012)
N = 126; older
adults with
memory
complaints
N = 27; Alzheimers
disease (AD)
N = 58; mild
cognitive
impairment
N = 61; dementia
N = 50; amnestic
mild cognitive
impairment
Intervention
Combined Mental
Activity & Aerobic
Exercise
Multimodal
Dual-task exercise
Dual-task kinetic
exercise
Dual-task exercise
Multicomponent
dual-task exercise
N: number of subjects; DTC: dual-task cost.

d: standard between-group effect size; CI: condence interval.
+: positive effect for intervention group; 0: no difference between groups.
Follow-up
Post-intervention
12 weeks
Post-intervention
16 weeks
Post-intervention
20 weeks
Post-intervention
12 weeks
Post-intervention 6
months, 12 months
Outcome Measures of Interest
Rey Auditory Verbal Learning Test

(RAVLT)
Verbal Fluency (letter & category)
Digit Symbol Substitution Test
(DSST)
Trail Making Test (TMT)
Eriksen Flanker Test (EFT)
Useful Field of View (UFOV)
Signicant
between-group effects
Effect sizes (95% CI)
Pre-intervention
Post-intervention
d = 0.35 (1.11 to
0.41)
d = 0.14 (0.89 to
0.62)
d = 0.04 (0.79 to
0.72)
d = 1.18 (0.372.01)
0
0
0
0
0
0
Frontal Assessment Battery (FAB)
Clock Drawing Test (CDT),
Symbol Search Subtest of WAIS-III

(Symbol)
Mini-mental State Examination

(MMSE)
Test of Everyday Attention (TEA)
Rey Auditory Verbal Learning Test
(RAVLT)
Rey-Osterrieth Complex Figure
Test (ROCFT)
Verbal Fluency Test (FAS)
Functional Rating Scale of
Symptoms of Dementia (FRSSD)
Functional Cognitive Assessment
Scale (FUCAS)
Wisconsin Card Sorting Test
(WCST)
Wechsler Adult Intelligence
Scale-Revised (WAIS-R)
Rivermead Behavioral Memory
Test (RBMT)
Boston Naming Test (BNT)
d = 0.40 (0.12 to 0.92)
d = 0.63 (0.111.16)
+
0
d = 0.08 (0.44 to 0.59)
d = 0.24 (0.28 to 0.76)
d = 0.01 (0.50 to 0.53)
d = 0.52 (0.0011.05)
+
+
d = 0.38 (0.14 to 0.90)

d = 0.17 (0.34 to 0.69)
d = 0.62 (0.091.14)
d = 0.59 (0.061.11)
Data not available for

calculation
d = 0.99 (0.391.59)
d = 0.96 (0.161.76)
d = 1.57 (0.712.44)
0
0
0
0
0
DTC Cognitive performance
DTC Combined motor-cognitive

performance
Mini-mental State Examination

(MMSE)
Immediate recall WMS-R
Delayed recall WMS-R
Digit symbol-coding (DSC) subset
WAIS-III
Letter verbal uency test (LVFT)
Category verbal uency test (CVFT)
Stroop Color and Word Test
(SCWT).
+ at 6 m & 12 m
d = 0.44 (0.440.67)
d = 0.11 (0.450.66)
+ at 6 m & 12 m
0
0
d = 0.09 (0.460.65)
d = 0.16 (0.390.72)
+ at 12 m
0
0
d = 0.16 (0.710.40)
d = 0.22 (0.340.77)
Kounti et al. (2011)
Subject
Table 5
Overview of quality rating of reviewed studies.
Study
Randomization
Concealed
allocation
Eligibility
criteria
Baseline similarity
Assessor
blinded
Care provider
blinded
Subject
blinded
Valid reliable
measures
Same follow-up
length
Outcome from
>85% subjects
Pre-specied
outcomes
Data
presentation
Intention-to-treat
Barnes et al.
(2013)
Yes
(computer
generated
sequence)
Unclear
(not stated)
Yes
Yes
(baseline
characteristics
presented)
Yes
(stated)
Unclear
(not stated)
Unclear
(not stated)
Yes
(reference
stated)
Yes
No
(21% drop-off
reported)
Yes
Yes
(stated)
Coelho et al.
(2012)
No
(assigned)
No
Yes
Unclear
(not stated)
No
Unclear
(not stated)
Yes
(reference
stated)
Yes
Yes
(number
presented)
Yes
Yes
(completer
comparison)
Fabre et al.
(2002)
No
(randomly
assigned)
No
Yes
Yes
(baseline
characteristics
presented
Yes
(baseline
characteristics
presented)
Yes
(mean
standardized
changes &
condence
intervals)
Yes
(mean & SD)
Unclear
(not stated for
outcome
measures)
Unclear
(not stated)
No
Yes
(reference
stated)
Yes
Yes
(stated)
Yes
Yes
(mean &
standard error)
Kounti et al.
(2011)
No
(assigned)
No
Yes
Yes
(completer baseline
comparison)
Yes
(stated)
No
No
Yes
Yes
(completer
comparison)
Yes
Yes
(mean & SD)
Legault et al.
(2011)
Unclear
(method of random
sequence
generation was not
stated)
No
(stated)
Unclear
(not stated)
Yes
Yes
(baseline
characteristics
presented)
Unclear
(not stated)
Unclear
(not stated)
Unclear
(not stated)
Yes
Yes
(data
reported)
Yes
Yes
(mean & SD;
mean change &
SE)
Yes
(stated)
No
(stated)
Yes
No
(stated)
Unclear
(not stated)
Unclear
(not stated)
Yes
Yes
(completer
comparison at
postintervention)
Yes
Yes
(z-score mean &
SD; effect size d)
Yes
(stated)
Schwenk et al.
(2010)
Yes
(numbered
container)
Yes
(by independent
person)
Yes
Yes
(stated)
No
Yes
(stated)
Yes
(reference
stated)
Yes
Yes
(data
reported)
Yes
Yes
(mean & SD)
No
(completer
analysis)
Suzuki et al.
(2012)
Unclear
(method of random
sequence
generation was not
stated)
Unclear
(not stated)
Yes
Yes
(baseline
characteristics
presented & with
adjustment in
analysis)
Yes
(stated baseline and
completer baseline
comparison)
Yes
(baseline
characteristics
presented)
Yes
(data &
reference
stated)
Unclear
(stated
reference
without
information)
Unclear
(not all stated)
Yes
(explicitly reported
same number of
subjects at pre and
post)
Yes
(completer
comparison)
Yes
(stated)
No
No
Yes
(reference
stated)
Yes
Yes
(data
reported)
Yes
Yes
(group mean
difference &
condence
intervals)
Yes
(stated)
Oswald et al.
(2006)
Sum score
11
69
70
Overall, the results of the reviewed studies in both populations

with and without cognitive impairment were conicting. Among
the three studies with cognitively healthy participants, one study
found no effects while two studies revealed signicant effects.
Fabre et al. (2002) reported a signicant effect on memory performance (d = 1.29). Oswald et al. (2006) found signicant 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 ve studies with cognitively impaired participants,
one study found no effect while four studies reported signicant
improvements in outcomes including cognitive-motor dual-task
cost (d = 0.99) in dementia; executive functions (d = 0.521.18) and
attention (d = 0.241.57) in MCI and AD; general cognitive functions (d = 0.110.63), language (d = 0.220.62), memory (d = 0.16)
and subjective rating of functional status (d = 0.59) in MCI.
4. Discussion
This systematic review examined the efcacy of combined cognitive and exercise training to improve cognitive functions in older
adults with and without cognitive impairment. Eight studies were
identied in this review, ve 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 degenerating cognitive continuum in populations with cognitive impairment
(Petersen, 2004). The studies were published within the past 10
years (20022013). This suggests that research to assess the impact
of combined cognitive and physical exercise on cognitive functions
in older adults is still in its edgling stage. The identied studies
were from a variety of mainly developed countries. The potential
benets of a combined intervention appears to be attracting the
interest of researchers throughout the world however more studies 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. Signicant improvements were found in two
out of the three studies with cognitively healthy populations and
in four out the ve studies with cognitively impaired populations.
The limited number and heterogeneity of the reviewed studies do
not enable any rm conclusion to be drawn. Nevertheless, specic
study characteristics can be identied in this review that may help
to promote intervention delity in future studies.
or exercise training) in the comparison groups as well as the nonspecic components (staff exposure or social contact) in the control
group. This design can greatly strengthen the validity and credibility of the ndings in the studies. Nevertheless, the exposure to
interventions varied between the combined and single interventions.
In a population with cognitive complaint, Barnes et al. (2013)
also used a multi-arm comparison group design and the intervention time were the same among all the intervention and
comparison groups. However, no signicant 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 benecial to the participants and
have potential impact on the outcomes. Therefore, a larger sample size would be required to have adequate power for detecting
signicant group differences (Baskin et al., 2003; Hart et al., 2008).
All the other four studies with cognitively impaired populations that used a dual-task exercise group compared with a control
group reported signicant ndings. It can be challenged that the
improvements observed in the studies may not be attributed to
the interventions or, more precisely, the specic 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-specic 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-specic 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 compared 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 positive ndings 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 benecial components
or moderators is important to validate the differential effects under
the investigation. As a result, appropriate activity selection in comparison control and a well-designed comparison group is crucial in
future studies on the efcacy of combined interventions.
4.1. Comparison and control group design

4.2. Study population screening
Appropriate design of the comparison and control groups is
important to allow critical investigation on the comparative effectiveness between the specic 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 signicant 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 subjective 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 combined intervention and the common components (single cognitive
Cognitive impairment/dementia may be caused by multiple

intertwined pathological factors (Stewart, 2002). Neurodegenerative conditions such as AD and cerebrovascular disease,
including subclinical brain injury, silent brain infarction, and clinically overt stroke, are the most common causes of cognitive
impairment/dementias in older individuals (Alzheimers Disease
International 2009; Gorelick et al., 2011). Vascular dementia (VaD)
is the second most common form of dementia after AD, accounting
for 2030% of the diseased population (Stewart, 2002). Importantly,
there is increasing evidence that vascular pathology frequently
co-exists with neurodegenerative pathology and most dementias 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
71
pathology (Roman, 1999). The pathogenic importance of vascular

contributions in cognitive impairment and dementia merits particular 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 Neurological and Communicative Disorders and Stroke-Alzheimers Disease
and Related Disorder Association (NINCDS-ADRDA) for dementia
(McKanhnn et al., 1984). Both of these studies performed neuroimaging examination, in addition to neuropsychological tests and
medical history, to conrm a diagnosis and reported exclusion of
persons with stroke. No information was reported on the pathological 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 Manual of Mental Disorders 4th edition (DSM-IV) criteria (American
Psychiaric Association, 2000) for diagnosis of Alzheimers disease,
which also excluded those with cognitive decits due to cerebrovascular disease. Barnes et al. (2013) also excluded those with
other neurological conditions in their study with a cognitive complaint populations. The diagnosis was based on interview, physician
diagnosis and neuropsychological assessment. Indeed, cerebrovascular 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 Alzheimers disease 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 Disorders 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 neuropathology evaluations or methods for operationalization of the screening
criteria. Silent infarct also has been found to inuence 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 contributes to the severity of cognitive impairment (Snowden et al.,
1997; Riekse et al., 2004; Petrovitch et al., 2005). Different subgroups may have different cognitive decits 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 importance in the investigation for effective preventative and treatment
strategies (Stephen et al., 2009). Clear identication and report on
the specic nature of the study population selected (neurodegenerative, vascular, mixed pathology) will be crucial to facilitate cross
study comparison and generalization of study ndings.
Praag et al., 2005). Neuroimaging studies in populations with cognitive 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 prepares 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 ndings,
the physical activity was set to precede the cognitive training or
the participants were re-exposed to cognitive training after physical 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 systematically reveal the potential impacts of training sequence on training
outcomes.
Suzuki et al. (2012) reported signicant group effects on general 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 (35 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 suggested 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 duration for cognitively impaired populations may need to be examined
in future studies.
4.3. Training sequence in combined intervention
4.6. Outcome measure selection
The sequence in delivering the cognitive training and exercise 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 neurogenesis in the brain and improves learning (Farmer et al., 2004; van
The studies by Suzuki et al. (2012) in amnestic MCI and Barnes

et al. (2013) in participants with memory complaints did not nd
any effects on executive functions. In contrast, the studies by Coelho
et al. (2012) in AD participants and Kounti et al. (2011) in MCI participants found signicant 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 decits have consistently been
4.4. Dual-task component

The high quality RCT by Schwenk et al. (2010) found signicant
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 individuals latent potential (Hertzog et al., 2009).
Although the ndings 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 learning 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
72
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 functions could be so subtle that some of the widely used executive
function tests may not be sensitive enough to detect the minimal changes (Espinosa et al., 2009; Pickens et al., 2010). Moreover,
the diversity of components under the umbrella of executive functions (Miyake et al., 2000) may further complicate the difculty in
assessing executive functions. The approach to use multiple outcome 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 specicity 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 decits 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; Grifth et al.,
2006). Indeed, visual spatial function is a very important cognition
in everyday functioning, for instance, navigating a car safely in driving 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 reect real benets and practical values of
an intervention only if the results of the intervention can be generalized to other non-trained tasks, settings and sustained over
time (Boelen et al., 2011; Glasgow et al., 2003). Previous cognitive 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 intervention 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 signicant effects. Oswald et al. (2006) reported positive generalization 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 nonstandardized subjective ratings.
In populations with cognitive impairment, all of the ve
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, traditional psychometric tests have been challenged for not being able
to adequately reect older adults functioning in a real everyday
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 practical 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 difculties in daily functioning, especially in complex everyday tasks that rely heavily on memory and reasoning (Aretouli
and Brandt, 2010; Prs et al., 2006). This imposes a potential
impact on the safety and quality of life of the person with cognitive impairment (Gauthier et al., 2006; World Health Organization
and Alzheimers 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 outcomes, 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 benets 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 number and heterogeneity of the reviewed studies did not allow critical
analysis of the results for different groups of populations with cognitive 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 coverage of all potential studies under this topic. Moreover, initial study
screening with title and abstract may lead to further limited cover
of possible intervention identication 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 signicant benets of
combined cognitive and exercise interventions on general cognitive functions, memory and functional status compared to active
control groups. Studies with cognitively impaired populations also
showed signicant 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. However, 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 rm conclusion on the efcacy of the combined cognitive and exercise intervention in older adults.
Conicts of interest
We declare that there are no conicts of interest.
Source of funding
This research received no specic grant from any funding agency
in the public, commercial, or not-for-prot 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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Effects of Combined Cognitive and Exercise Interventions On Cognition in Older Adults With and Without Cognitive Impairment - A Systematic Review

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Ageing Research Reviews 15 (2014) 6175

Contents lists available at ScienceDirect

Ageing Research Reviews

Effects of combined cognitive and exercise interventions on cognition

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175

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

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175

and functioning (Clare and Woods, 2003; Martin et al., 2006).

derived to compare groups before and after the intervention.

2.4. Quality assessment

2.1. Search strategies

A systematic computer-based search of Cinahl, Medline,

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175

3.3.2. Studies with cognitively impaired participants

3.4.2. Studies with cognitively impaired participants

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175

Fabre et al. (2002)

CG: No training, but meeting

AT: brisk walking and/or jogging

MT: eight themes: perceptive

Mean age (years):

MMSE score: not conducted

Legault et al. (2011)

N = 73; United States

Mean age (years):

Mean age (years): 79.5

CG: Health education;

MMSE score: Not conducted

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

3.6. Outcome measures and intervention effects

Kounti et al. (2011)

Schwenk et al. (2010)

Suzuki et al. (2012)

N = 126; older adults with memory

Independent Home-based + center-based

N = 27; Alzheimers disease (AD); Brazil

N = 58; mild cognitive impairment; Greece

N = 61; dementia; Germany

N = 50; amnestic mild cognitive

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

Total intervention hours (h)

Control/comparison (total hours)

CG: Wait-list control

CG: Motor placebo group: low

Health education; 3 sessions

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175

Coelho et al. (2012)

Data not available

CG: control group; CG*: comparison group.

Cognitive Function Composite Score

Data not available

Oswald et al. (2006)

Combined Aerobic (AT)

3.7. Methodological quality of included studies

Outcome Measures of interest

Signicant between-group effects

Effect sizes (95% CI)

3.6.2. Studies with cognitively impaired participants

(compared to CG & CG*)

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

L.L.F. Law et al. / Ageing Research Reviews 15 (2014) 6175

Barnes et al. (2013)

Coelho et al. (2012)