Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis

Highlights

• Combined cognitive and physical exercise interventions can improve global cognition in older adults with MCI or dementia.

• Benefits of combined interventions on activities of daily living and mood emphasize its clinical relevance.

• Future research on the superiority of combined interventions over single interventions is warranted.

Abstract

Combined cognitive and physical exercise interventions have potential to elicit cognitive benefits in older adults with mild cognitive impairment (MCI) or dementia. This meta-analysis aims to quantify the overall effect of these interventions on global cognitive functioning in older adults with MCI or dementia. Ten randomized controlled trials that applied a combined cognitive-physical intervention with cognitive function as an outcome measure were included. For each study effect sizes were computed (i.e., post-intervention standardized mean difference (SMD) scores) and pooled, using a random-effects meta-analysis. The primary analysis showed a small-to-medium positive effect of combined cognitive-physical interventions on global cognitive function in older adults with MCI or dementia (SMD[95% confidence interval] = 0.32[0.17;0.47], p < 0.00). A combined intervention was equally beneficial in patients with dementia (SMD = 0.36[0.12;0.60], p < 0.00) and MCI (SMD = 0.39[0.15;0.63], p < 0.05). In addition, the analysis showed a moderate-to-large positive effect after combined cognitive-physical interventions for activities of daily living (ADL) (SMD = 0.65[0.09;1.21], p < 0.01)and a small-to-medium positive effect for mood (SMD = 0.27[0.04;0.50], p < 0.01). These functional benefits emphasize the clinical relevance of combined cognitive and physical training strategies.

Introduction

Due to the aging population, the number of people with mild cognitive impairment (MCI) or dementia is expected to grow (World Health Organisation and Alzheimer’s Disease International, 2012). Currently there are about ten million new cases of dementia each year, a number which will increase to approximately 131.5 million prevalent dementia cases in 2050 (Alzheimer’s Disease International, 2015). These rapidly growing numbers will have a large societal impact, placing a high economic burden on health care (Alzheimer’s Disease International, 2015, Winblad et al., 2016). Therefore, the World Health Organization (WHO) stresses to take global action against cognitive decline and dementia, encouraging governments worldwide to focus on prevention, disease-modifying therapies and improving health care services (World Health Organization, 2015).

Mild cognitive impairment (MCI) is the transitional phase between normal cognitive functioning and dementia, characterized by cognitive decline that is larger than expected considering a person’s age and education, though without notably interference in daily-life activities (Gauthier et al., 2006). The annual conversion rates from MCI to dementia ranges from 5 to 20%, depending on the sample studied and the follow-up duration (Langa and Levine, 2014). Dementia is characterized by progressive and severe cognitive decline, motor deficits and/or behavioural problems causing a decline in activities of daily living (ADL) (Alzheimer’s Association, 2014). A variety of neuropatholologies underlie dementia syndromes, with Alzheimer’s disease being the most common cause in older adults, accounting for 60–80% of all dementia cases, followed by vascular dementia (Alzheimer’s Association, 2014). Thus far, pharmacological therapies solely alleviate dementia symptoms, but fail to modify disease progression (Feldman et al., 2007, Kavirajan and Schneider, 2007, Versijpt, 2014)

Recent meta-analyses show that physical exercise may help to preserve or even improve cognitive function in healthy older adults (Angevaren et al., 2008, Colcombe and Kramer, 2003, Smith et al., 2010, Voss et al., 2011). There is evidence that exercise increases the volumes of the prefrontal cortex (Colcombe et al., 2006) and the anterior hippocampus (Dietrich et al., 2008, Erickson et al., 2011), and may enhance neurogenesis (Nokia et al., 2016) and angiogenesis (Lange-Asschenfeldt and Kojda, 2008). Furthermore, exercise reduces cardiovascular risk factors (Rovio et al., 2005). In contrast, research on the effects of physical exercise in older adults with MCI or dementia are less abundant and vary in efficacy (Forbes et al., 2015, Gates et al., 2013, Groot et al., 2016, Heyn et al., 2004). The large variability in exercise protocols, study populations and treatment compliance complicate interpretation of the results (Forbes et al., 2015, Groot et al., 2016, Heyn et al., 2004).

Possibly, the neural and cognitive benefits elicited by physical activity can be enhanced by adding exposure to a cognitively challenging environment (Fabel and Kempermann, 2008, Fabel et al., 2009, Olson et al., 2006). Experimental animal studies have shown that physical activity and environmental enrichment induce hippocampal neurogenesis via different pathways, and a combination results in greater benefits than either physical activity or an enriched environment alone (Fabel et al., 2009, Olson et al., 2006). In line, a meta-analysis of Zhu et al. (2016) revealed significant benefits of combined cognitive and physical interventions, compared with both single exercise training and a control group, on overall cognitive function in healthy older adults. A qualitative review of Law et al. (2014) shows some benefits of combined interventions in cognitively impaired populations, however the evidence was limited when the evaluation included comparison with active control groups. Moreover, conclusions drawn from this qualitative review were based on reported levels of statistical significance without considering the magnitude of the observed effects. Therefore, a quantitative meta-analysis including the most recent studies is needed to clarify the efficacy of combined cognitive and physical exercise interventions on global cognitive function in older adults with MCI or dementia.

The primary objective of this meta-analysis is to quantify the overall effect of combined cognitive and physical exercise interventions on global cognitive function in older adults with MCI or dementia. Secondary objectives are to (1) assess the effect of combined cognitive and physical exercise interventions on the cognitive domains of memory and executive function/attention, (2) determine whether combined interventions positively influence activities of daily living (ADL) and (3) evaluate the efficacy of combined interventions on mood.