Elsevier

Ageing Research Reviews

Volume 25, January 2016, Pages 13-23
Ageing Research Reviews

Review
The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials

https://doi.org/10.1016/j.arr.2015.11.005Get rights and content

Highlights

  • Epidemiological studies have suggested an association between increased physical activity and a reduced risk of dementia.

  • The current meta-analysis shows that physical activity interventions are beneficial for cognition in patients with dementia.

  • This effect of physical activity interventions is driven by aerobic exercise, and is independent of dementia type.

  • High frequency interventions do not result in additional effects on cognition compared to low frequency interventions.

  • Future studies would benefit from assessing neuroimaging/molecular markers to determine optimal intervention characteristics.

Abstract

Non-pharmacological therapies, such as physical activity interventions, are an appealing alternative or add-on to current pharmacological treatment of cognitive symptoms in patients with dementia. In this meta-analysis, we investigated the effect of physical activity interventions on cognitive function in dementia patients, by synthesizing data from 802 patients included in 18 randomized control trials that applied a physical activity intervention with cognitive function as an outcome measure. Post-intervention standardized mean difference (SMD) scores were computed for each study, and combined into pooled effect sizes using random effects meta-analysis. The primary analysis yielded a positive overall effect of physical activity interventions on cognitive function (SMD[95% confidence interval] = 0.42[0.23;0.62], p < .01). Secondary analyses revealed that physical activity interventions were equally beneficial in patients with Alzheimer's disease (AD, SMD = 0.38[0.09;0.66], p < .01) and in patients with AD or a non-AD dementia diagnosis (SMD = 0.47[0.14;0.80], p < .01). Combined (i.e. aerobic and non-aerobic) exercise interventions (SMD = 0.59[0.32;0.86], p < .01) and aerobic-only exercise interventions (SMD = 0.41[0.05;0.76], p < .05) had a positive effect on cognition, while this association was absent for non-aerobic exercise interventions (SMD = -0.10[−0.38;0.19], p = .51). Finally, we found that interventions offered at both high frequency (SMD = 0.33[0.03;0.63], p < .05) and at low frequency (SMD = 0.64[0.39;0.89], p < .01) had a positive effect on cognitive function. This meta-analysis suggests that physical activity interventions positively influence cognitive function in patients with dementia. This beneficial effect was independent of the clinical diagnosis and the frequency of the intervention, and was driven by interventions that included aerobic exercise.

Introduction

Dementia is a clinical syndrome characterized by cognitive decline, motor deficits and/or behavioral problems, causing a decline in daily functioning (Scott and Barrett, 2007). Various neuropathologies can underlie dementia syndromes but the most prevalent cause is Alzheimer’s disease (AD), accounting for 60–70% of the cases (Reitz et al., 2011). Other types of dementia include vascular dementia, dementia with Lewy bodies and frontotemporal dementia. Advancing age is the main risk factor for most sporadic forms of dementia, and with the ever increasingly aging population worldwide the prevalence of dementia is expected to nearly double from 35.6 million cases in 2010 to 65.7 million in 2030 (Prince et al., 2013). This expected increase will have profound social and financial consequences, and dementia has therefore been denoted a public health priority by the World Health Organization (Wortmann, 2012).

Currently, no disease modifying drugs for dementia are available and pharmacological treatment is limited to therapies that alleviate the symptoms. However, these treatments are not efficacious in all patients and may introduce undesirable side-effects (Galimberti and Scarpini, 2010). Non-pharmacological interventions, such as physical activity interventions (Deslandes et al., 2009, Hooghiemstra et al., 2012, Kirk-Sanchez and McGough, 2014, Sofi et al., 2011), are therefore appealing alternatives or add-ons. Epidemiological studies have shown that increased lifetime engagement in physical activities reduces the risk of dementia-onset in cognitively normal elderly persons (Abbott et al., 2004, Buchman et al., 2012, Chang et al., 2010, Hamer and Chida, 2009, Larson et al., 2006, Laurin et al., 2001, Podewils et al., 2005, Rovio et al., 2005, Scarmeas et al., 2009, Taaffe et al., 2008, Yaffe et al., 2001). Experimental animal studies have identified several molecular mechanisms such as enhancement of neurotrophin levels (Adlard et al., 2005, Berchtold et al., 2005, Berchtold et al., 2002, Gómez-Pinilla et al., 2007, Macias et al., 2007, Radak et al., 2010, Swain et al., 2003, Vaynman et al., 2003), neurogenesis (Kronenberg et al., 2006, Sahay et al., 2011, Van Praag et al., 2005, Van Praag et al., 2000, Van Praag et al., 1999) and vascularization (Black et al., 1990, Ding et al., 2004, Isaacs et al., 1992, Kleim et al., 2002, Swain et al., 2003) that may explain this beneficial effect. Moreover, physical activity may even reduce aggregation of pathogenic proteins (Adlard et al., 2005, Belarbi et al., 2011, Leem et al., 2009 Yuede et al., 2009), mediate neuroinflammation (Belarbi et al., 2011) and inhibit neuronal dysfunction (Um et al., 2011).

Physical activity thus seems to enhance brain vitality and several studies have investigated whether physical activity interventions are sufficient to slow down cognitive decline once the clinical diagnosis of dementia has been established. Results have been mixed, however, as some studies indeed showed a positive effect of physical activity interventions (Farina et al., 2014, Hess et al., 2014, Heyn et al., 2004, Scherder et al., 2014), while others did not (Forbes et al., 2015, Littbrand et al., 2011, Öhman et al., 2014). In the current study, we performed a meta-analysis of randomized controlled trials that investigated the effect of physical activity on cognitive function in patients with dementia. Secondary objectives of this meta-analysis were to assess whether the effect of physical activity on cognitive function was (1) comparable across different types of dementia, (2) dependent on aerobic and/or non-aerobic exercise, and (3) affected by the frequency of the intervention.

Section snippets

Study selection procedure

We searched the Pubmed/MEDLINE, Web of knowledge/science, Science Direct and ALOIS databases for eligible studies published between January 1st 1960 and May 1st 2015. We used the following (combination of) search terms: “physical activity”, “exercise(s)”, “(cardiovascular) fitness”, “(an/non-) aerobic”, “danc(e/ing)”, “walk(ing)”, “train(ing)”, “yoga”, “Tai Chi”, “strength”, “Alzheimer(’s)”, “dementia”, “cognition”, “cognitive” and “MMSE”. We included only peer-reviewed articles (written in

Study selection

The final selection for this meta-analysis comprised 18 studies including a total of 802 patients with dementia, 433 patients in intervention groups and 369 patients serving as controls (Table 1, Fig. 1) (Arcoverde et al., 2014, Bossers et al., 2015, Cheng et al., 2014, Christofoletti et al., 2008, Cott et al., 2002, Hokkanen et al., 2008, Holthoff et al., 2015, Kemoun et al., 2010, Kwak et al., 2008, Miu et al., 2008, Steinberg et al., 2009, Stevens and Killeen, 2006, Van de Winckel et al.,

Discussion

In this meta-analysis of RCTs, we found a positive overall effect of physical activity interventions on cognitive function in patients with dementia. This effect was driven by interventions that included aerobic exercises and was independent of the type of dementia. Furthermore, we found that in this specific study population, high frequency interventions were not characterized by greater effects on cognitive function than low frequency interventions. Finally, we observed that the positive

Conflict of interests

The authors report no conflict of interests

Acknowedgements

We would like to thank all corresponding authors who provided additional data that was not available in the original manuscript. This research was funded by Marie Curie FP7 International Outgoing Fellowship ​628812 (to R.O.) and the donors of [Alzheimer’s Disease Research], a program of BrightFocus Foundation (to R.O.). Research of the VUMC Alzheimer center is part of the neurodegeneration research program of the Neuroscience Campus Amsterdam. The VUMC Alzheimer center is supported by Alzheimer

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