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. 2018 Aug 3;2018(8):CD008198. doi: 10.1002/14651858.CD008198.pub2

Physical activity for improving cognition in older people with mild cognitive impairment

Vasiliki Orgeta 1,✉, Ciaran E Abbey 2, Martin Orrell 3
PMCID: PMC6513658

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

A primary objective of the present review is to evaluate and quantify the effectiveness of physical activity interventions in improving cognition in older adults with MCI. A secondary objective comprises the evaluation of the effectiveness of physical activity in improving non cognitive outcomes in older adults with MCI. The present review should aid practitioners in terms of choosing interventions for people with MCI, as well as extending current research.

Background

The primary aim of this review is to quantitatively summarize current evidence in the effects of physical exercise‐based interventions in improving cognition in older adults with mild cognitive impairment.

It is well documented that cognitive ability decreases with increasing age, with several studies reporting an objective decline in cognitive performance around the age of 50 (Schaie 1993). In recent years, the concept of Mild Cognitive Impairment (MCI) has been used to describe the population of older adults who experience memory complaints within the context of normal everyday functioning, absence of dementia and objective evidence of a cognitive deficit (Larrieu 2002). The definition of MCI was originally constructed to increase the predictive value for Alzheimer's Disease (AD) (Ritchie 2000), and it is now widely documented that MCI may represent a transitional state between normal aging and dementia (Petersen 1999).

One of the risk factors associated with cognitive decline and may be amenable to change in interventions is physical activity, with several studies showing that increased levels of physical activity (Coley 2008) are associated with preserved cognitive function. A recent meta‐analysis concluded that physical exercise improves cognitive ability in healthy aging (Colcombe 2003), and studies have shown that physical exercise is associated with increases specifically in speed of information processing, auditory and visual attention (Angevaren 2008).

Observational studies show that higher levels of physical activity improve general cognitive function (Weuve 2004) and that older adults who engage in walking exercises are less likely to develop dementia over a follow‐up period of 6 years than those who are not (Abbott 2004). Several prospective studies have demonstrated that physically active people have a lower risk of developing AD and related cognitive disorders when compared with those who are less physically active (Laurin 2001; Hamer 2009; Larson 2006; Yaffe 2001). Physical activity interventions have been found to improve cognitive function in older adults without cognitive impairment in several domains of cognition such as verbal fluency (Emery 1998), cognitive speed (Bakken 2001), executive functioning (Kramer 2001), and memory (Fabre 1998).

A large number of RCTs have been conducted suggesting that physical activity interventions improve cognitive functioning in older adults with cognitive impairment. For example, physical activity has been associated with improvements in communication in older adults with dementia (Friedman 1991), verbal fluency (Van de Winckel 2004) and executive function (Stevens 2006), whereas some studies have reported no effects (Cott 2002). RCTs investigating the benefits of physical exercise in older adults with MCI have shown that physical activity improves executive function (Scherder 2005). Physical exercise such as walking has also been associated with improvements in memory and attention (van Uffelen 2008a) in older adults with a diagnosis of MCI.

Description of the condition

The diagnosis of MCI has been based on memory complaints within the context of normal everyday functioning. MCI is thought to represent a state between normal cognition and dementia, where the cognitive deficits observed cannot be explained by age, educational status or medical diagnosis. Evidence suggests that Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) have similar anatomical locations, with the degree of impairment differentiating between a diagnosis of MCI versus AD (Jelic 1996; Jelic 2000). Although individuals with MCI are at an increased risk of developing dementia (Petersen 1999), specifically AD (Larrieu 2002), an important characteristic of the syndrome is its inherent heterogeneity, with cerebrovascular disease (Kryscio 2006; Solfrizzi 2004), depression (Visser 2005), metabolic, sensory and nutritional impairments (Gauthier 2005) purported to contribute to the underlying etiology. Several studies have shown that hormonal replacement therapy may contribute to cognitive decline in women (Ryan 2008), although protective positive effects have also been reported (Yaffe 1998).

MCI was originally classified by Petersen 1999 which proposed that MCI consists of the following diagnostic criteria: (1) memory complaint, (2) normal activities of daily living, (3) normal general cognitive functioning, (4) abnormal memory for age, and (5) patient not meeting the criteria for dementia. Subsequent developments of the concept have classified the syndrome into three main subtypes; amnestic MCI or single memory MCI, multiple‐domain MCI, and single non memory MCI (Petersen 2003; Visser 2005). Even with these criteria, however, there is a lack of consensus on the definition so rates of MCI have been estimated as ranging between 3% and 53% in older adults over 65 years (Larrieu 2002). For the purpose of the present review all types of MCI will be included, with an aim of separating amnestic MCI and multiple‐domain and single non memory‐domain MCI.

Description of the intervention

A wide variety of interventions have been used in studies investigating the effects of exercise in cognition in older adults with and without cognitive decline (van Uffelen 2008). There are a number of ways of classifying physical activity interventions. In the present review, physical exercise will be categorized by type, intensity and inclusion of psychological elements. Classification of type of physical activity will be based on previous research according to which, physical activity comprises of four types, aerobic, strength, flexibility and balance exercise as well as combinations of the several types (i.e. flexibility and balance, strength and flexibility, or strength, flexibility and balance, van Uffelen 2008). Classification of intensity of physical exercise will comprise physical activity of low (Scherder 2005; McMurdo 1993; Latham 2003), moderate (Forbes 2008; van Uffelen 2008a) and high intensity (Lautenschlager 2008). The last category will comprise physical activity interventions of a more complex nature in which physical activity is combined with psychological elements such as Tai Chi (Nowalk 2001) and walk and talk groups (Cott 2002), consistent with previous research emphasizing the psychological dimension of physical exercise (Rolland 2008). As previous systematic reviews examining effects of exercise in older adults without known cognitive impairment (Angevaren 2008), in the present review, any type of physical activity aimed at improving cardiorespiratory fitness, will be included.

How the intervention might work

A number of physiological mechanisms have been proposed that may account for the relationship between physical exercise and increased cognitive ability. Longitudinal studies (Fratiglioni 2004) investigating the effects of exercise on cognition and dementia, have pointed towards three prevailing theoretical hypotheses. According to the vascular hypothesis, physical activity acts as a protective factor of cognitive decline by reducing the risk of cardiovascular disease often associated with dementia (Gauthier 2005), by maintaining cerebral blood flow (Swain 2003). The cognitive reserve hypothesis posits that physical exercise promotes and improves the functioning of non‐neuronal components of the brain resulting in the new formation of neurons (Pham 2002), in several areas of the brain, specifically in the hippocampus (Vaynman 2005; van Praag 2005). Finally, the stress hypothesis, argues that psychological mechanisms, such as relaxation and stress reduction, which are promoted by physical activity, benefit cognitive functioning, in line with evidence suggesting that failures to adapt positively to stressors may contribute to cognitive dysfunction (Belanoff 2001). Contrary to the hypotheses of stress and cognitive reserve, which do not specify the type of physical activity, the cardiovascular (aerobic) fitness hypothesis implies that aerobic exercise benefits cognition due to improvements in aerobic fitness. Despite evidence suggesting that aerobic fitness, is associated with morphological changes in the brain such as increases in brain volume (Colcombe 2006), recent reviews conclude that improvements in aerobic fitness do not mediate the beneficial effects of (aerobic) exercise on cognition (Etnier 2006; Angevaren 2008).

Why it is important to do this review

The results of the present review will be useful for establishing guidelines and recommendations for exercise training in older adults with MCI. Given documented evidence that older adults with MCI are at higher risk than the normal older adult population for developing dementia (Petersen 2003), effective therapeutic interventions are significant in terms of preventive approaches. The present review will be informative since current evidence is inconclusive in terms of effective treatments for MCI (Rosenberg 2006). For example, data from RCTs document that Vitamin E and cholinesterase inhibitors are not associated with protective effects for progression of MCI to AD (Raschetti 2007). In addition, several studies have associated pharmaceutical interventions with significant side effects within the context of minor and short lived beneficial effects (Petersen 2005). For individuals with MCI, physical activity programs may aid in terms of improving cognition and prevent further cognitive decline. Identification of therapeutic interventions therefore, may reduce distress for patients and prolong autonomy, consistent with evidence demonstrating that physical activity may also result in benefits in functional and behavioural outcomes (Heyn 2004).

Objectives

A primary objective of the present review is to evaluate and quantify the effectiveness of physical activity interventions in improving cognition in older adults with MCI. A secondary objective comprises the evaluation of the effectiveness of physical activity in improving non cognitive outcomes in older adults with MCI. The present review should aid practitioners in terms of choosing interventions for people with MCI, as well as extending current research.

Methods

Criteria for considering studies for this review

Types of studies

The inclusion criteria for studies to be included are: RCTs that include a nonintervention control or comparison group or control, and those that provide adequate information in terms of results and description of the study (i.e. studies that report means, standard deviations (SDs), t test or F test, and n values), or those studies that information can be obtained by the researchers. Trials with clearly reported or inadequate concealment will also be included in the analysis. RCTs with mixed populations (e.g. normal cognition, mild cognitive impairment) will be included, providing that data from patients with MCI are available or can be obtained from the authors. Ongoing studies will be included in this review. Studies that are not RCTs will be excluded.

Types of participants

The inclusion criteria for participants are:

  • Older adults (55 years of age or older) with a MCI diagnosis. These criteria will be the original set out by (Petersen 1999)  (no dementia, memory complaint, preserved general cognitive function, intact activities of daily living and impaired memory for education and age), as well as those proposed in later developments of the MCI concept (classifying the syndrome into three main subtypes; amnestic MCI or single memory MCI, multiple‐domain MCI, and single non memory MCI (Visser 2005; Petersen 2003)

  • Any setting (e.g. home, community, institution)

Types of interventions

Studies that evaluate the effects of physical activity interventions in improving cognitive function in MCI will be considered. Physical activity is defined as any form of exercise program or rehabilitative exercise, fitness, or recreational therapy (i.e. weight training, strength and balance training, walking, aerobic exercise, anaerobic exercise). The latter will be compared with no intervention, with control conditions including a non‐specific therapy, with interventions targeted at other domains (i.e. programs of social or mental activities) or usual care. All types of modality of physical activity intervention will be included, such as individual versus group. The physical activity treatment will be of any intensity, duration or frequency.

Types of outcome measures

All studies included must report an outcome measure of cognitive or non cognitive domains, measured by a standardized test.

Primary outcomes

  • Measures of cognitive functioning, including memory (e.g. Memory Functioning Questionnaire, word list recall, name recall, Rivermead Behavioural Memory Test), attention (e.g. verbal series attention test, visual detection), executive functioning (e.g. Trail Making Test) or language will comprise the primary outcome measures. 

Secondary outcomes

  • Non cognitive outcomes such as measures of well‐being, quality of life, and every‐day functioning will compose the secondary outcomes. Examples include daily activity level (ADLs), self care inventory, functional assessment of communication skills, psychogeriatric behavioral rating (e.g. London Psychogeriatric Rating Scale), affective status (e.g. depression scale, self‐rating of depression), frequency of agitation, self‐reported functional ability, daytime behavioral observations of sleep.

  • Rates of conversion to dementia or rates of institutionalisation as well as impact on carers if available. 

Search methods for identification of studies

Electronic searches

See Cochrane Dementia and Cognitive Improvement Group methods used in reviews.

The Cochrane Dementia and Cognitive Improvement Group's Specialized Register will be searched using the terms: MCI or "mild cognitive impairment" or AAMI or "age‐associated memory impairment" or AACD or "age‐associated cognitive decline" or CIND or SMC or "subjective memory complaints" or MCIa or "cognitive impairment not dementia" or "preclinical AD" or ""pre‐clinical AD" or "preclinical Alzheimer" or "preclinical Alzheimer" or "episodic memory", in combination with the following terms: walking OR physical activity OR physical therapy OR exercise* OR fitness OR rehabilitation OR aerobic OR flexibility OR motor activit* OR leisure activit* OR physical fitness OR physical endurance OR exercise tolerance OR strength OR balance OR exercise test OR aerobic OR aerobic capacity OR physical capacity OR physical performance OR training OR cycling OR swim* OR gym* OR walk* OR danc* OR yoga OR "tai chi".

This Register contains records from The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS and many ongoing clinical trials databases and grey literature sources. We will also search these electronic databases for the most recent records.  Appendix 1 shows the search strategy to be used in MEDLINE. In summary the following databases will be searched: Health Care databases, Conference Proceedings, Theses, Ongoing Trials (UK, Netherlands, USA/International). The corresponding authors of identified RCTs that will be potentially suitable for inclusion will be contacted to request additional information on related new, unpublished, or in press studies.

Searching other resources

We will search identified citations for additional trials. We will contact the corresponding author of identified trials for additional references and unpublished data.

Data collection and analysis

Selection of studies

Two reviewers will search titles and abstracts in order to identify studies that may meet the inclusion criteria. Once all trials have been identified, the three reviewers (VO, CR and MO) will work independently to determine which of the studies identified meet the criteria for inclusion. Two reviewers (VO and CR) will independently review all the trials for inclusion in the review. Reviewers will work independently in order to decide which of the studies meet the quality criteria, according to the recommended approach for assessing risk of bias in Cochrane Reviews in the Cochrane Handbook for Systematic Reviews of Interventions, which would involve describing what was reported to have happened in the study and assigning judgments relating to each risk of bias. If required, additional information about the procedure of randomization will be requested from relevant authors.

Data extraction and management

A standardized data extraction form will be used, which will be piloted before use. The extracted information will include data on methods, participants, interventions, outcomes and results. In relation to methods used data will be extracted on methodologies used for randomization. Items related to participant characteristics are number, gender and age of participants, diagnostic criteria, and other items of importance (number of people screened for inclusion, the number fulfilling inclusion criteria, depression, cardiovascular risk factors and use of hormone replacement therapy for female participants). Data relevant to interventions used will be specifics of duration, intensity, type, frequency and mode of physical activity, primary and secondary outcomes (including type of measurement), adverse events and other trial characteristics (e.g. number of participants dropping out during and after treatment, blindness, intention to treat or available case analysis, as well as data on costs whenever possible). Data from the studies will be extracted and entered into RevMan. To ensure that accurate data are extracted, the third reviewer (MO) will check the extracted data and any discrepancies will be resolved through discussion. The types of data to be extracted are, means at endpoint, and SDs for continuous data. In addition, the reviewers will use the odds ratio in measuring treatment effects, in the case of binary outcomes, by calculating a weighted estimate of the treatment effect in each RCT.

Assessment of risk of bias in included studies

The recommended approach by the Cochrane Handbook for Systematic Reviews of Interventions, for assessing risk of bias will be employed, which addresses six specific domains, sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting and other issues. In each domain reviewers will work independently in relation to input of entries in a risk of bias table. In cases where no information is available in order to make a judgment, this would be explicitly stated. Plots of intervention effect estimates stratified according to risk of bias will be conducted where appropriate to examine the potential of bias in terms of affecting the results of the meta‐analysis.

Measures of treatment effect

Summary statistics for each RCT will include mean value of the outcome measurements in each intervention group, standard deviation of the outcome measurements in each intervention group, and the number of participants on whom the outcome was measured in each intervention group (in the case of continuous data). When the pooled studies use the same rating scale or assessment measure, the treatment difference for any outcome will be the weighted mean difference, whereas when pooled studies use different scales, the absolute mean difference divided by the standard deviation will be used. In the case of binary data, the reviewers will extract the number of participants in each treatment group, and the numbers of those with the outcome measures of interest. The latest available assessment prior to randomization of participants (but no later than two months) is defined as the baseline assessment.

Dealing with missing data

Missing data and dropout rates will be assessed for each individual RCT. The final number of participants included in the final analysis will be reported as a proportion of all participants in the study. Variation in the magnitude of missing data may add to heterogeneity and will therefore be controlled if possible in the analyses.

Assessment of heterogeneity

In the present review overall estimates of treatment effects will be calculated. A fixed effects model will be used to represent overall estimate effects. Tests of heterogeneity will be performed through the use of I2 statistic. If heterogeneity in treatment effect is evident across the RCTs then the reviewers will either perform meta‐analysis by using a random‐effects model, or will combine homogenous results.

Subgroup analysis and investigation of heterogeneity

Depending on the availability of studies, a potential subgroup analysis is that of weight bearing and cardiovascular exercise. Further potential subgroup analyses include intensity of physical activity (e.g. minutes/session), duration (e.g. total number of weeks) and frequency (e.g. sessions/week). Given previous prospective studies suggesting that strenuous and not moderate physical exercise is associated with less cognitive decline (Albert 1995), the comparisons of most interest are those of intensity of physical activity and weight bearing versus cardiovascular exercise. If sufficient RCTs are identified, publication bias will be examined by a funnel plot (Egger 1997). The reviewers will seek statistical advice from the CDCIG.

Sensitivity analysis

If necessary sensitivity analyses will be performed in order to examine potential effects amongst excluded RCTs (e.g. those of low methodological quality). Further sensitivity analyses will be conducted if data allows in order to assess whether methodological differences (e.g. cognitive test used, duration of RCT, cutoff scores of MMSE, diagnostic criteria, baseline characteristics of participants) amongst studies influence treatment effects. After the primary analyses, the authors would perform sensitivity analysis to examine how results might be affected if studies of high risk of bias were included in the analyses.

Acknowledgements

We would like to thank the Cochrane Dementia and Cognitive Improvement Review Group and Helen Collins, Review Group Co‐ordinator of the CDCIG.

Appendices

Appendix 1. MEDLINE search strategy

1 "mild cognitive impairment" ti, ab
2 MCI ti, ab
3 "age‐associated memory impairment” ti, ab
4 AAMI ti, ab
5 "age‐associated cognitive decline" ti, ab
6 AACD ti, ab
7 "subjective memory complaints" ti, ab
8 "cognitive impairment not dementia" ti, ab
9 CIND ti, ab
10 "preclinical AD" ti, ab
11 “pre‐clinical AD" ti, ab
12 "preclinical Alzheimer"
13 "episodic memory"
14 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13
15 Motor activity [MeSH]
16 Walk* ti, ab
17 “Physical activity” ti, ab
18 “Physical therapy” ti, ab
19 Exercis*
20 Fitness ti, ab
21 Rehabilitation ti, ab
22 Aerobic ti, ab
23 Strength ti, ab
24 Flexibility ti, ab
25 “Motor
*” ti, ab
26 “leisure activit*” ti, ab
27 “Physical fitness” ti, ab
28 “Physical endurance” ti, ab
29 “Exercise tolerance” ti, ab
30 “Exercise test” ti, ab
31 “Aerobic capacity” ti, ab
32 “Physical capacity” ti, ab
33 “Physical performance” ti, ab
34 “Physical training” ti, ab
35 Cycling ti, ab
36 Swim* ti, ab
37 Gym* ti, ab
38 Danc* ti, ab
39 Yoga ti, ab
40 “tai chi” ti, ab
41 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40
42 14 and 41
43 “randomized controlled trial *”  ti, ab, pt
44 “randomised controlled trial*” ti, ab
45 “controlled clinical trial*” ti, ab, pt
46 “randomi*” ti., ab
47 (double blind* or single blind* or triple blind*).ti, ab.
48 (crossover or cross‐over) ti, ab
49 43 or 44 or 45 or 46 or 47 or 48
50 42 and 49
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What's new

Date Event Description
3 August 2018 Amended This protocol, published in 2010 was withdrawn from the Cochrane Library in August 2018 due to lack of progress.
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Contributions of authors

VO ‐ correspondence; drafting review versions; search for trials; selection of RCTs; extraction of data; entry of data; data analysis; interpretation of statistical analyses; updating review.

CR ‐ selection of RCTs; extraction of data; interpretation of statistical analyses; updating review.

MO ‐selection of RCTs; extraction of data; interpretation of statistical analyses; updating review.

Declarations of interest

None known.

Notes

This protocol, published in 2010 was withdrawn from the Cochrane Library in August 2018 due to lack of progress.

Withdrawn from publication for reasons stated in the review

References

Additional references

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