The Effects of a Multicomponent Dyadic Intervention With Physical Exercise on the Cognitive Functioning of People With Dementia: A Randomized Controlled Trial

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Anna-Eva Prick
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Jacomine de Lange
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Erik Scherder
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Jos Twisk
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Anne Margriet Pot
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The objective was to evaluate the effects of a multicomponent dyadic intervention on the cognitive functioning of people with dementia living at home in a randomized controlled trial. People with dementia and their family caregivers (n = 111) were randomly assigned to 8 home-based sessions including physical exercise and support or a minimal intervention consisting of monthly written information bulletins and monthly phone calls. Memory, executive functioning (EF), and attention were assessed at baseline, and after 3 (postmeasurement) and 6 months (follow-up). Data were analyzed by using generalized estimating equations (GEE). A small, significant effect was found on attention. No effects were found on memory and EF. Finding only a small significant effect might be explained by the ineffectiveness of the intervention, but also by moderate treatment adherence or a lack of room for improvement because half of the people with dementia were already receiving care in a day care facility.

Today, 47.5 million people live with dementia worldwide and this number is estimated to increase to 131.5 million by the year 2050 (Prince et al., 2015). Consistent with policy initiatives to stimulate the ‘self-reliance’ of older people resulting in providing care at home where possible, the proportion of people with dementia living in residential care has started to decrease in high-income countries (Prince et al., 2015). Currently, in high-income countries, two-thirds of the people living with dementia are cared for at home, with up to 90% of their care provided by informal caregivers, such as partners, other family members, and friends (Prince, Prina, & Guerchet, 2013). For caregiver-care recipient dyads living at home, reaching the best possible functional ability and quality of life are generally perceived as primary goals. However, the onset of cognitive impairment in people with dementia quickly compromises their ability to carry out complex but essential tasks. At a later stage, they need increasing help with basic personal care. Interventions reducing the cognitive decline of people with dementia and support for caregivers to deal with the consequences of dementia are highly needed.

In recent decades, many psychosocial supporting interventions have been developed (Brodaty & Arasaratnam, 2012; Moniz-Cook, Vernooij-Dassen, Woods, Orrell, & Interdem Network, 2011), showing more effectiveness than pharmacological interventions for people with dementia. Nonpharmacological interventions, including physical activity interventions, are therefore promising alternatives (Kirk-Sanchez & McGough, 2014; Sofi et al., 2011): ‘physical activity’ includes body movement that contracts muscles to burn more calories than a body would normally do so just to exist at rest (Chodzko-Zajko et al., 2009). In recent years, the number of studies that have examined the relationship between physical activity and cognition in aging has increased (Lista & Sorrentino, 2010; McDonnell, Smith, & Mackintosh, 2011; van Uffelen, Paw, Hopman-Rock, & van Mechelen, 2008). Experimental animal studies have identified several molecular mechanisms that may be an explanation for this beneficial effect, such as the enhancement of neurotrophin levels, neurogenesis, and vascularization (Barnes, 2015; Swain et al., 2003). Several studies showed the beneficial impact of planned, structured, repetitive, and purposeful physical activity, so called physical exercise (Chodzko-Zajko et al., 2009), on cognitive functioning in older people without cognitive impairment (Angevaren, Aufdemkampe, Verhaar, Aleman, & Vanhees, 2008; Colcombe & Kramer, 2003; Erickson et al., 2011; Kramer et al., 1999; Smith et al., 2010). Because brain volume is linked with cognition (Roe et al., 2011), it is not surprising that studies show a positive relationship between physical exercise and cognitive functioning in old age (Kramer, Erickson, & Colcombe, 2006; Voelcker-Rehage, Godde, & Staudinger, 2010). Especially, endurance exercise and strength training seem to diminish the impairment of cognitive functions in older people (Savela, Komulainen, Sipilä, & Strandberg, 2015).

Physical exercise thus seems to enhance brain vitality in older people. However, among people with dementia, the results of the effects of physical exercise on cognition are still ambiguous (Forbes, Forbes, Blake, Thiessen, & Forbes, 2015; Littbrand, Stenvall, & Rosendahl, 2011; Öhman, Savikko, Strandberg, & Pitkälä, 2014). Studies conducted on older people with mild cognitive impairment (MCI) report some positive effects of physical exercise on global cognition, executive function (EF), attention and memory (delayed recall) (Öhman et al., 2014; Zheng, Xia, Zhou, Tao, & Chen, 2016). A recent meta-analysis showed that aerobic exercise led to an improvement in global cognitive ability and had a positive effects with a small effect size on memory in people with MCI (Zheng et al., 2016). In the studies that showed a beneficial impact, the aerobic exercise could be of any style (for example, yoga, Tai Chi, treadmill) for at least 4 weeks with more than one exercise session per week compared with no specific exercise intervention. Another meta-analysis showed that physical exercise significantly improved global cognition, executive functioning (EF), and attention in people with MCI and/or dementia, although participants with MCI seemed to benefit more due to better adherence to activity (Hess, Dieberg, McFarlane, & Smart, 2014). The physical exercise included walking, varied intensity aerobic training, strength training, flexibility training, postural balance training, and Tai Chi at least 2–4 times per week, and each lasted from 30–60 min per session. The results of a meta-analysis examining the relationship between walking and EF in people with and without cognitive impairment showed that only people without cognitive impairment benefit from walking (Scherder et al., 2014). Two recent reviews reported the positive effect of physical exercise on cognitive function in people with dementia (Farina, Rusted, & Tabet, 2014; Groot et al., 2016). The meta-analysis of Groot et al. (2016), including studies in which the intervention solely focused on physical activity, with no minimal duration limit, revealed a positive overall effect of physical activity interventions on global cognitive function in people with dementia. This effect was driven by interventions that included aerobic exercises and was independent of the type of dementia. The systematic review of Farina et al. (2014) revealed preliminary evidence of the beneficial effects of physical exercise (lasted a minimum of 4 weeks and were solely exercise based) on global cognition for people with dementia. However, Farina et al. (2014) concluded that the variation between study designs makes conclusions regarding the optimum intervention on cognitive outcome in people with dementia difficult. In contrast, a recent Cochrane systematic review revealed no evidence of benefit from physical exercise (aerobic, resistance, or combined exercise regimen) for at least 12 weeks on global cognition in people with dementia (Forbes et al., 2015). The findings are still inconsistent in older people with cognitive impairment, e.g., dementia, partly by a lack of good quality randomized controlled trials (RCTs), variations in study design, and methods of analysis.

In examining the effects of physical exercise on cognitive functioning, few home-based studies have been performed among people with dementia living in the community (Forbes et al., 2015; Forbes, Thiessen, Blake, Forbes, & Forbes, 2013). One example of these few perfomed home-based studies with physical exercise is the one developed by Vreugdenhil, Cannell, Davies, and Razay (2012). The results of this RCT showed that a 4-month daily physical exercise program (strength and balance training in addition to walking) for people with dementia living at home under the supervision of their informal caregivers is effective in improving cognition, physical function, and activities of daily living (ADL; Vreugdenhil et al. 2012). Another promising example of a home-based intervention with a physical exercise component is the one developed by Teri et al. (2003). This study showed a beneficial impact of physical exercise (aerobic/endurance activities, strength training, balance, and flexibility training for at least 30 min per day of moderate intensity) combined with teaching caregivers how to manage behavioral problems on the physical functioning of people with dementia living at home as well as on their mood (Teri et al., 2003). While the multicomponent intervention with physical exercise of Teri et al. (2003) may also benefit cognitive functioning in people with dementia, this has not been studied.

Our RCT, on a translated and adapted version of the multicomponent intervention of Teri et al. (2003), was to study its impact on the physical functioning and mood of people with dementia and on the psychological distress of caregivers (Prick, de Lange, Scherder, & Pot, 2011; Prick, de Lange, Scherder, Twisk, & Pot, 2016; Prick, de Lange, Twisk, & Pot, 2015; Prick, de Lange, van’t Leven, & Pot, 2014). In addition, we hypothesized that the multicomponent intervention—also including a physical exercise component—might have a beneficial impact on cognitive functioning (i.e., memory, EF, and attention) of people with dementia as well.

Methods

Trial Design

This study was a randomized controlled trial with three measurements: baseline, 3 months (postmeasurement), and 6 months (follow-up) measurement. Informed consent was obtained from both the person with dementia and the caregiver individually before the start of the study. After baseline assessment, dyads were randomly assigned to the intervention (n = 57) or comparison group (n = 54), which featured a minimal intervention.

Participants

Via Alzheimer Cafés (easily accessible meetings for people with dementia, their caregivers, and others), case managers, flyers, and advertisements in newspapers and on the Internet, 146 persons with dementia and their caregivers were recruited between November 2008 and June 2012 throughout the Netherlands.

The inclusion criteria for people with dementia were a diagnosis of dementia made by a physician (for instance, a general practitioner, psychiatrist, geriatrician, or a neurologist), minimum age of 55 years, and living at home with a caregiver willing to participate in the training sessions. Exclusion criteria were the use of antidepressants, the presence of psychotic symptoms, Mini Mental State Examination (MMSE) score < 14, and receiving more than 2 days care in a day care facility.

Their family caregivers were defined as spouses or adult relatives who live with or spend a minimum of 4 hours every day with the person with dementia. Caregivers were excluded in case of physical disorders that hamper assistance with the exercises, presence of psychotic symptoms, and use of antidepressants.

Study Setting

The data collection and intervention took place in the homes of the participants.

Intervention

Dyads allocated to the intervention group received a multicomponent dyadic intervention consisting of physical exercise training and support existing of psycho-education, a communication skills training, and a pleasant activities training. A personal coach who visited the dyads in their own homes for eight 1-hr-long sessions during 3 months delivered this multicomponent dyadic intervention. During the first month, the coach visited the dyads weekly followed by biweekly sessions over the next 8 weeks. During the physical exercise training, four types of exercises (flexibility, strengthening, balance, and endurance) were gradually instructed and practiced (Table 1). The goal of the physical exercise component was to motivate dyads who have not been physically active to complete 30 min of active exercise at least 3 days a week. Dyads who were already active were encouraged to increase or maintain their activity to complete 30 min of active physical exercise at least 3 days a week and preferable on most days of the week. Each physical exercise training started with careful stretching, providing a warming up for the other physical exercises, and increasing participants’ awareness of their muscles. The goal of strength training was to maintain mobility and to safely perform daily activities such as standing up from a chair and walking. Balance exercises were designed to improve the safeness of participants’ mobility. Endurance exercises were intended to maintain or improve overall physical health and mood. All physical exercises focused on ease, availability, and pleasantness (Teri, Logsdon, & McCurry, 2008). During the instruction visits, caregivers were taught by the coach to guide the person with dementia during the performance of the physical exercises. Each physical exercise was first demonstrated by the coach, and then practiced by the person with dementia while the caregiver assisted the person with dementia and, if possible, the caregiver performed the physical exercises as well. To improve the attractiveness of the physical exercises for people with dementia, we added and integrated materials such as a ball, weights, and elastics to the original physical exercises based on a Dutch exercise protocol for people with dementia designed by physiotherapists (Vliegendhart & Van der Mark, 2009). Caregivers in the intervention group completed daily logs to monitor their adherence to the physical exercise homework in the absence of the coach.

Table 1

Description of the Physical Exercises

 EquipmentMain Procedure FeaturesExercises
In general Participants were observed and trained by coaches while learning the exercises. The coach had to train and monitor the caregiver in conducting the exercises.

The caregiver was stimulated to participate as much as possible in performing the physical exercises together with the person with dementia.

Visual and verbal cues were given as often as necessary to help the participant perform the exercises safely and correctly.

Daily record of performance should be written on the exercise log.
All exercises
Strengthening exercisesAnkle and wrist weights, elastics, chairStrength exercises had to follow the endurance/balance exercises

Exercises had be performed on three nonconsecutive days each week

Exercises would last 10–15 min

Participants had to work toward a goal of one set of 10–12 repetitions for each muscle group

Participants had to start without weights. At each session, if possible, the participant had to add weight.
Dorsiflexion

Knee extension

Plantar flexion

Hip flexors

Knee flexion

Hip abduction

Hip extension
Balance exercisesChair, table for balance, stairs or step, ballExercises had be performed on three nonconsecutive days each week, preferably as a warm up for strengthening exercises or cool-down for aerobic activity

Exercises would last 10–15 min
Transfer exercises (transfer from a seated to a standing position)

Functional base-of-support

Duo exercises
Flexibility exercisesChair, wallAll participants had to cool down for approximately 5–10 min

Each stretch had to be done slowly and without ballistic movement for 15 s or more
Chest stretch

Neck stretch

Shoulder stretch

Ankle stretch

Quadriceps stretch
Endurance exercises The coach had to observe the participant while introducing the walking exercises near their home. Once trained, the caregiver had to observe and assist the person with dementia as necessary.

The participant had to walk a minimum of three nonconsecutive days.

The participant had to start walking at their natural place and gradually walk faster to increase their aerobic state.

Participants had to increase the time they walk as quickly as possible until a goal of 20 min was achieved.
Walking

Alongside physical exercise, the dyads received support through psycho-education, a communication skills training and a pleasant activities training. The goal of psycho-education was to educate the dyad about dementia and its impact on the person with dementia and the caregiver and how to deal with it. In the communication skills training, the coach discussed techniques for facilitating the dyad’s communication. Pleasant activities training stimulated the planning of one’s own chosen pleasant activities in daily life for the person with dementia and the caregiver individually, and for them together, to reduce psychological distress. When the caregiver and/or person with dementia were unable to identify pleasant activities, a list with pleasant activity ideas, including ideas such as parlor games, listening to music, or exercise, was available.

Alongside the instruction visits, all dyads received a user manual with a detailed description of the intervention. The manual included session-specific worksheets with specific information and psycho-education for each visit. Furthermore, illustrations of the physical exercises, safety instructions, and easy-to-read instructions were included.

Comparison Group With Minimal Intervention

Participants who were assigned to the comparison group received a minimal intervention in addition to the usual care. The minimal intervention consisted of written information bulletins sent to the dyads on a monthly basis with general information about dementia such as information about driving and general health (three in total) and monthly phone calls by one of the coaches (three in total). The goals of these maximal 10-min phone calls were to listen to the family caregiver and to show empathy. Participants allocated to the comparison group were offered the multicomponent dyadic intervention at the conclusion of the study.

Baseline Variables

To collect general and demographic information, questions were asked concerning age, sex, birth date, education, dementia type, comorbidity, medication use, cognitive functioning, and the client-caregiver relationship. The education level was determined on a 7-point scale varying from less than elementary school (0) to technical college and university (6) (Verhage, 1964). In people with dementia, the global level of cognitive functioning was determined using the Dutch version of the MMSE (Folstein, Folstein, & McHugh, 1975; Kok & Verhey, 2002) and The Global Deterioration Scale (GDS) to distinguish between the global stages from normality to severe dementia (Reisberg, Ferris, de Leon, & Crook, 1982). Medication use (antidementia medication and cardiovascular medication) was coded according to the Anatomical Therapeutic Chemical (ATC) Classification System, which is an international standard for drug utilization studies. Comorbid conditions were asked from the caregiver and categorized according to the main categories based on the International Statistical Classification of Diseases (ICD). The body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Furthermore, the status of Apolipoprotein Epsilon 4 (ApoE4) was determined as a baseline variable because ApoE4 carriers show an increased risk of cognitive decline and, thereby, may show a greater response from physical activity than noncarriers (Foster, Rosenblatt, & Kuljiš, 2011; Nichol, Deeny, Seif, Camaclang, & Cotman, 2009). Buccal swabs were taken by making use of Catch-all collection swabs (Epicentre, Madison, WI, USA). DNA was isolated from the swab (Ilveskoski, Lehtimäki, Erkinjuntti, Koivula, & Karhunen, 1998). The ApoE genotype was indicated as ApoE4 present or absent.

Outcomes

Assessment of Cognitive Functioning

To assess the aspects of cognitive functioning different neuropsychological tests were administered.

Memory—The 8 Words Test of the Amsterdam Dementia Screeningtest (ADS; Lindeboom & Jonker, 1989), consisting of three parts, was used to measure episodic anterograde memory. During the first part, eight unrelated words are read aloud to the subject five times. Immediately after each presentation, recall is tested, with the total number of words recalled after the five trials being used as the score (immediate recall, score range: 0–40). In addition, recall is again tested after a delay of 10 min (delayed recall, score range 0–8). After this, a recognition test is followed in which the eight words are intermixed with eight distracters (recognition score, score range 0–16).

To measure visual nonverbal long-term episodic memory, the Face and Picture Recognition of the Rivermead Behavioural Memory Test (RBMT; Van Balen & Wimmers, 1993; Wilson, Cockburn, & Baddeley, 1985) were used. During Face Recognition the participant is shown 10 faces, one at a time, for 5 s each. After a short interval, the participant is asked to recognize the faces between 10 other faces. The outcome measure is the number of faces correctly recognized minus the faces that were incorrectly recognized (score range 0–20). During Picture Recognition, the participant is shown 20 cards with drawings of objects and is asked to remember the objects. After a short interval the participant has to choose between 40 cards with objects and has to point out the objects already shown. The outcome measure is the number of objects correctly recognized minus the objects that are incorrectly recognized (score range 0–40).

Executive function (EF)—The Digit Span Test Backward is part of the Wechsler Memory Scale–Revised (WMS-R; Wechsler, 1987). Increasingly long sequences of random numbers are read aloud by the examiner. In the backward version, the participant is asked to repeat the digits in reverse order immediately after oral presentation by the examiner. Work-memory is measured by digit span backward, which is considered to appeal to EF. The outcome measure is the number of series correctly reproduced (score range 0–21).

To measure the ability to plan a strategy to solve a problem, the Key Search Test of the Behavioural Assessment of the Dysexecutive Syndrome (BADS; Wilson, Alderman, Burgess, Emslie, & Evans, 1996) was used. The participant is asked to search for an imaginary key that they have lost in a field (a square on a piece of paper). By drawing their search route, an indication of search strategy and planning ability can be deduced. The outcome measure is based on a number of eight criteria, such as efficiency and effectiveness (score range 0–16).

Category Fluency is a subtest from the Groninger Intelligence Test (GIT; Snijders & Verhage, 1983). This test requires a strategic search mechanism to retrieve information from semantic memory and was used to measure categorization abilities. The participant is asked to name as many animals and professions as possible during 1 (separate) min. The total number of animals and professions produced is the outcome measure (score range 0–21).

Attention—The Digit Span Test Forward is part of the WMS-R (Wechsler, 1987). Increasingly long sequences of random numbers are read aloud by the examiner. In the forward version, the participant is asked to repeat the digits immediately after oral presentation by the examiner. Short-term memory was measured by digit span forward, considered to appeal to the efficiency of attention, i.e., freedom from distractibility. The outcome measure is the number of series correctly reproduced (score range 0–21).

Randomization

After the baseline assessment, the dyads were randomly assigned by blocked randomization (block size 20) to the intervention or comparison group. The allocation schedule was made by an independent researcher with a computer-generated block randomization using random Allocation Software (Version 1; M.Saghaei, University of Medical Sciences, Isfahan, Iran).

Blinding

Dyads and their intervention instruction coaches were aware of the treatment assigned. Although examiners were blinded to the group allocation and the dyads were asked not to disclose their group allocation at the start of each measurement, group allocation became clear to the examiners in practice.

Statistical Methods

All the data were analyzed using IBM SPSS Statistics 20 (Chicago, IL). Descriptive statistics were calculated for the participants in the intervention and comparison group and all of the (outcome) variables were analyzed for differences between comparison and intervention group by means of independent-sample t-tests for continuous variables and χ2 tests for categorical variables. Baseline characteristics of dropouts and completers were compared using independent-sample t-tests and χ2 tests. Scores on memory and EF neuropsychological tests were transformed in z-scores, after a factor analysis; the mean of these scores resulted in a memory domain and an EF domain. The memory domain was computed by five neuropsychological test scores, i.e., three test scores of the eight words test (direct recall, delayed recall, and recognition), picture recognition, and face recognition (combined Cronbach’s alpha .76 in this study). The Executive Function domain was computed by the key search test, digit span backward, and two category fluency tests (combined Cronbach’s alpha .72 in this study).

The effectiveness of the intervention on all outcomes was evaluated between the two groups by using generalized estimating equations (GEE) (Liang & Zeger, 1986; Twisk, 1997, 2003; Zeger, Liang, & Albert, 1988). GEE is a longitudinal regression technique that takes into account the dependency of the observations within the subject by estimating the average correlation over time (i.e., an exchangeable working correlation structure). The advantage of using GEE above the more classical general linear models (GLM) for repeated measures is that GEE is capable of handling missing data and that it provides direct estimates of the effect of the intervention. In the present study, for all GEE analyses, an exchangeable correlation structure was used (i.e., the correlations between subsequent measurements are assumed to be the same, irrespective of the length of the measurement interval) and all analyses were adjusted for the baseline value of the outcome variable. The characteristics of the people with dementia (age, sex, dementia type, daycare, past level of physical exercise in the childhood [<18 years], education level, GDS score, APOE-4, baseline values for MMSE, BMI, comorbidity and polypharmacy use) were identified a priori as potential covariates. We conducted a crude analysis and an adjusted analysis to examine the effects over time. The crude analyses determined the effect of the intervention over time while controlling for the baseline values. The adjusted analyses determined the intervention effect over time while the covariates were added to the model (and again adjusting for baseline outcomes). In both crude and adjusted analyses, first an overall intervention effect was estimated and, secondly, the intervention effect at different time-points. Furthermore, at all of the stages of data analysis, intention-to-treat analyses were performed, including all the participants as originally allocated after randomization. Significance was set at .05. If significant, an overall effect size for the specific cognitive outcome domain was calculated according to Cohen’s d. The Cohen’s d was calculated by dividing the overall mean difference between the groups (expressed as regression coefficient) by the overall SD of the observed data. Effect sizes ≥ 0.8 are assumed to be large, effect sizes between 0.5–0.8 are moderate, and effect sizes between 0.2–0.5 are assumed to be small (Hedges & Olkin, 1985).

Compliance Analyses Including Per-Protocol Analysis

In addition to intention-to-treat (ITT) analysis, compliance analyses were performed for dyads using GEE. First, we evaluated the outcomes of dyads who completed all of the homework assignments of practicing exercise and planning pleasant activities: 30 min of active physical exercise at least 3 days a week and implementation of pleasant activities in daily life for both the person with dementia and the caregiver for at least 6 weeks (‘per protocol principle’). Second, we evaluated the outcomes of the dyads who completed their physical exercise homework according the intervention protocol (completed 30 min of active exercise for at least 3 days a week) based on the Seattle protocols of Teri et al. (2008) for increasing physical activity in individuals with cognitive impairment. Finally, we evaluated the outcomes of the dyads who planned their pleasant activities according to the protocol (implemented pleasant activities in daily life for both the person with dementia and the caregiver for at least 6 weeks). All of the dyads included in all three compliance analyses completed a minimum of six of the eight home visits.

Subgroup Analyses

We performed four subgroup analyses on the three cognitive outcome domains: (1) an APOE-4 subgroup analysis (carrier versus noncarrier) because APOE-4 carriers are at higher risk for cognitive decline, but respond better to physical activity interventions to stimulate cognition (Foster et al., 2011; Kivipelto et al., 2008); (2) a dementia onset subgroup analysis (early onset < 65 versus late onset ≥ 65), because people with early onset dementia (<65) show a more rapid cognitive decline than people with late onset dementia (≥ 65) (Hooghiemstra, Eggermont, Scheltens, van der Flier, & Scherder, 2012; van der Vlies et al., 2009); (3) a depression baseline scores subgroup analysis (Cornell score > 10 versus Cornell score ≤ 10), because the comorbidity of cognitive impairment and depression (a Cornell score > 10 probably major depressive episode) is associated with greater cognitive and functional decline (Potter & Steffens, 2007); (4) a dementia type subgroup analysis (Alzheimer versus other dementia types), because several observational studies have found that the preventive effects of physical exercise may be weaker for people with vascular dementia than for people with Alzheimer’s disease (Forbes et al., 2013; Rockwood & Middleton, 2007). In all subgroup analyses, the specific subgroup was selected from all study participants and the difference between the groups over time was then compared.

Ethical Aspects

The Medical Ethics Committee of the VU University Medical Center approved the study protocol (registration number 2008/320).

Results

Enrollment and Dropouts

Of the 146 dyads recruited for this study, in total, 111 dyads fulfilled the inclusion criteria and were randomized to the intervention group (n = 57) or comparison group (n = 54) (Figure 1). In total, 98 (88%) people with dementia completed post measurement and 85 (77%) people with dementia completed a 6-month follow-up measurement. During the first 3 months, five people with dementia dropped out from the intervention group and eight from the comparison group. After 6 months, seven people with dementia dropped out from the intervention group and four from the comparison group. The dropout reasons were health problems, burden, death of the person with dementia, nursing home placement, and hospitalization. The dropout rate was not different between the intervention and comparison group. Furthermore, we found no significant differences on any of the outcome measures and baseline characteristics between people with dementia dropouts and people with dementia completers.

Figure 1
Figure 1

—Flow chart of the present study. CG = caregiver; PD = person with dementia; ITT = intension-to-treat analysis.

Citation: Journal of Aging and Physical Activity 25, 4; 10.1123/japa.2016-0038

Sample Characteristics

At baseline, people with dementia were primarily male spouses (63%) with dementia of the Alzheimer type (70%). As shown in Table 2, the age ranged from 57 to 90 years (M = 77; SD = 7.46), mean MMSE score ranged from 14 to 30 (M = 21; SD = 5.19), mean BMI score ranged from 19 to 39 (M = 24; SD = 3.26), and the mean GDS score ranged from 3 to 6 (M = 4.5; SD = 0.619). On average, they used two to three different types of antidementia and cardiovascular medication. Half of the people with dementia (47%) made use of day care, whereof a small number of the people with dementia (6%) for 1 day and the majority (41%) for 2 days. Their caregivers were primarily female spouses (72%) with an age range from 35−92 years (M = 72, SD = 10.09). Their mean Centre for Epidemiologic Studies-Depression score at baseline ranged from 5 to 35 (M = 11; SD = 7.70). No significant differences were found between the comparison and the intervention group at baseline in any of the sample characteristics and outcomes in persons with dementia or caregivers, showing that the randomization was successful. The mean scores and standard deviations for all raw outcomes at different assessment moments are shown in Table 3.

Table 2

Baseline Characteristics of the People With Dementia and Their Caregivers

 Total Sample (n = 111)Intervention (n = 57)Comparison (n = 54)P Value (2-Sided)
People with dementia
Gender (n, %)   .05
Male70 (63.1)31 (54.4)39 (72.2) 
Female41 (36.9)26 (45.6)15 (27.8) 
Dementia type (n, %)   .49
Alzheimer78 (70.3)42 (73.7)36 (66.7) 
Vascular17 (15.3)9 (15.8)8 (14.8) 
Other16 (14.4)6 (10.5)10 (18.5) 
APOE-4 carrier (n, %)   1
No53 (47.7)27 (50)26 (48.1) 
Yes55 (49.5)27 (50)28 (51.9) 
Daycare (n, %)   .66
No57 (51.4)29 (52.7)28 (51.9) 
1 day7 (6.3)5 (9.1)2 (3.7) 
2 days45 (40.5)21 (38.2)24 (44.5) 
Exercise past < 18 years old (n, %)   .87
No17 (15.3)9 (15.8)8 (15.4) 
Moderate: 1–2 times a week31 (27.9)15 (26.3)16 (30.8) 
Intensive: 3 or more times a week61 (55)33 (57.9)28 (53.8) 
Drugs for cardiovascular system (ATC_C)   .53
No51 (45.9)17 (38.6)24 (47.1) 
Yes60 (54.1)27 (61.4)27 (52.9) 
Drug Tacrine, ATC:N06DA01 (n, %)    
No111 (100)57 (100)54 (100) 
Yes0 (0)0 (0)0 (0) 
Drug Donepezil, ATC:N06DA02 (n, %)   .49
No110 (99.1)5753 
Yes1 (0.9)01 
Drug Rivastigmine, ATC:N06DA03 (n, %)   1
No82 (73.9)32 (72.7)37 (72.5) 
Yes29 (26.1)12 (27.3)14 (27.5) 
Drug Galantamine ATC:N06DA04 (n, %)   .81
No86 (77.5)34 (77.3)38 (74.5) 
Yes25 (22.5)10 (22.7)13 (25.5) 
Age (range 57–90) (mean, SD)77 (7.46)76 (7.61)78 (7.17).1
Education (range 0–6) (mean, SD)4.01(1.43)3.91 (1.42)4.11 (1.45).47
Comorbidity (range 0–5) (mean, SD)1.65 (1.26)1.68 (1.2)1.61 (1.3).76
Polypharmacy use (range 0–9) (mean, SD)2.78 (1.99)2.74 (1.8)2.83 (2.1).80
BMI (kg/m2) (mean, SD)24 (3.26)24 (2.36)24 (3.98).26
MMSE (range 14–30) (mean, SD)21(5.19)21 (4.86)21 (5.56).91
Global Deterioration Scale (mean, SD)4.53 (0.62)4.54 (0.61)4.53 (0.64).94
EF (z-score baseline) (mean, SD)0.02 (2.39)−0.12 (2.06)0.17 (2.72).54
Memory (z-score baseline) (mean, SD)0.12 (3.49)0.15 (3.33)0.08 (3.67).92
Attention (z-score baseline) (mean, SD)0.00 (1.00)0.04 (1.07)−0.04 (0.93).83

Abbreviations: BMI = body mass index; MMSE = Mini Mental State Examination; EF = executive functioning.

Table 3

Unadjusted Means (M) and Standard Deviations (SD) on the Dependent Variables

Intervention Group (n = 57)Comparison Group (n = 54)
Baseline (T0)Post (T1)Follow-up (T2)Baseline (T0)Post (T1)Follow-up (T2)
MSDMSDMSDMSDMSDMSD
Memory
8 WT immediate17.546.6716.908.0517.677.8417.438.4418.428.7418.0310.35
8 WT delayed0.841.461.001.760.741.551.061.831.502.281.151.99
8 WT recognition11.743.8711.373.6311.053.7711.284.5312.262.6410.824.96
RBMT faces29.605.9730.166.0930.445.6630.654.8030.935.6630.705.48
RBMT pictures66.9610.6365.9511.8464.3913.0066.3111.264.2812.0966.3712.94
EF
BADS key search5.953.866.003.925.403.256.584.756.504.385.403.25
GIT fluency animals10.515.2510.465.759.565.6711.157.4210.226.5011.257.10
GIT fluency professions7.004.067.785.367.214.647.785.368.005.978.326.21
WMS-R digit span BW5.462.535.422.395.022.535.572.815.582.915.702.74
Attention
WMS-R digit span FW10.683.2010.923.3510.403.7610.462.7910.392.8610.533.45

Abbreviations: 8WT = 8 Words Test; BADS = Behavioural Assessment of the Dysexecutive Syndrome; GIT = Groninger Intelligence Test; RBMT = Rivermead Behavioural Memory Test; T1 = 3 months; T2 = 6 months; WMS-R = Wechsler Memory Scale-Revised.

Intention-to-Treat Analysis

As shown in Table 4, when adjusting for a person with dementia characteristics, GEE analysis among 111 dyads revealed a significant effect of the multicomponent dyadic intervention on attention. On other cognitive domains, no significant effects were found.

Table 4

Intention to Treat GEE Intervention Effects at Baseline and 3 and 6 Months on Cognitive Functioning

GEE Analysis – Intention To Treat*n = 111 Dyads (57 Intervention Group/54 Comparison Group)
Crude ModelAdjusted Model
Outcome Measureβ (95% CI)pEffect Size dβ (95% CI)PEffect Size d
EFOverall0.03 (−0.40 to 0.46).89 0.03 (−0.38 to 0.44).89 
 T1−0.07 (−0.58 to 0.45).80 0.02 (−0.39 to 0.43).94 
 T20.12 (−3.81 to 0.61).65 0.02 (−0.39 to 0.42).94 
MemoryOverall−0.04 (−0.66 to 0.58).90 0.16 (−0.53 to 0.85).65 
 T10.35 (−0.47 to 1.17).40 0.14 (−0.55 to 0.83).70 
 T2−0.42 (−1.16 to 0.32).26 0.09 (−0.59 to 0.76).80 
AttentionOverall0.50 (−0.21 to 0.31).700.050.25 (0.01 to 0.48).040.25
 T10.03 (−0.27 to 0.34).84 0.25 (0.01 to 0.48).04 
 T20.07 (−0.22 to 0.35).65 0.25 (0.01 to 0.48).04 

Abbreviations: β = regression coefficient; GEE = generalized estimating equations; CI = Confidence Interval; EF = Executive Functioning; T1 = 3 months; T2 = 6 months.

Note. Reference group is comparison group at all measurements; Crude model: adjusted for baseline value of outcome measure. Adjusted model: model further additionally adjusted for age, sex, education level, dementia type, APOE-4, daycare, past level of physical activity in the childhood, Global Deterioration Scale score at T0, MMSE score at T0, comorbidity, and polypharmacy use. The effect size is presented as an overall effect size represented as Cohen’s d.

Compliance Analyses

As shown in Table 5, for the experimental group, nine dyads (15.8%) were fully compliant with the intervention (completed 8 home visits, exercised 3 times a week and planned pleasant activities according to the protocol: per protocol analysis) and 43 dyads (75.4%) were moderately compliant with the protocol (any combination of dyads who completed 1–8 home visits, exercised 1–3 times a week, and planned pleasant activities during 1–6 weeks). Five dyads (8.8%) did not start with the home visits because of death or nursing home placement of the person with dementia. Compliance analyses, including a ‘per protocol analysis’, showed no benefits of the multi-component dyadic intervention on any of the outcomes of the people with dementia.

Table 5

Compliance With the Homework (Exercise and Pleasant Activities Planning) and the Presence of Home Visits of Dyads Assigned to the Experimental Group

Homework & Home Visits Compliance (n = 57)n (%)
Home visits compliance (8 home visits)
Completed: 6–8 home visits44 (77.2)
Partly completed: <6 home visits8 (14)
Not started with intervention: no home visits5 (8.8)
Homework exercise compliance (3 times a week)
3 or more times weekly exercise23 (40.4)
1–2 times weekly exercise16 (28.1)
0 times weekly exercise (intervention [partly] received)18 (31.5)
Planning pleasant activities compliance (without assistance coach during at least 6 weeks)
Planned pleasant activities according protocol:>6 weeks18 (31.6)
Partly planned pleasant activities: 1–6 weeks9 (15.8)
No pleasant activities planned (intervention [partly] received)25 (43.9)
No pleasant activities planned (not started with intervention)5 (8.8)
Combined homework & home visits compliance
Fully compliance according protocol: completed 8 home visits, exercise 3 times a week, and planned pleasant activities9 (15.8)
Moderate compliance: any combination of dyads who completed 1–8 home visits, exercised 1–3 times a week and planned pleasant activities during 1–6 weeks43 (75.4)
Not started with intervention5 (8.8)

Subgroup Analyses

When adjusting for a person with dementia characteristics, all subgroup analyses among 111 dyads revealed a significant effect of the multicomponent dyadic intervention on attention. On the other cognitive domains, no significant effects were found in the subgroup analyses.

Discussion

In this RCT, we studied the effects of a multicomponent dyadic intervention with physical exercise training and support on cognitive performance outcomes (memory, EF, and attention) of community-dwelling people with dementia. People with dementia who participated in this study were primarily community-living males diagnosed with Alzheimer’s disease. Their family caregivers were primarily female spouses. Intention-to-treat GEE analyses showed a significant effect of the multicomponent dyadic intervention on the attention of people with dementia measured with the digit span forwards. No significant effects were found on the memory and EF domains.

Attention

There have been rather few trials of multicomponent physical exercise interventions for community-dwelling people with dementia and with mixed results. To our knowledge, this is the first multicomponent dyadic home-based intervention with physical exercise that studied the benefits on cognitive performance in community-dwelling people. Previous intervention studies on single exercise intervention have reported benefits of physical exercise on other attention tests in people with dementia, but not specifically on the digit span forward test (Hess et al., 2014; Yágüez, Shaw, Morris, & Matthews, 2011). Yágüez et al. (2011) found that a 6-week nonaerobic movement-based exercise to activate balanced and equal muscles on both sides of the body is effective in sustained attention (Rapid Visual Information Processing test) in community-living people with Alzheimer's disease. The systematic review of Hess et al. (2014), focusing on both aerobic and nonaerobic physical exercise, showed significant improvements on attention (ADS-6 drawing alternative sequences).

There has been a hypothesis put forward trying to explain why physical exercise could improve attention. As memory and attention deficits are among the first clinical manifestations to develop dementia (Mol, de Jonghe, & Lindeboom, 2000), it is possible that physical exercise stimulation may increase temporary arousal, stimulating attention (Coull, 1998). It might be that this temporary arousal benefits concentration, which is necessary for the digit span forward test. In this study, we were focused on the impact of a multi-component intervention, as previous research showed that these interventions had more impact on the health of people with dementia and their caregivers than single component interventions (Acton & Kang, 2001; Ayalon, Gum, Feliciano, & Areán, 2006; Brodaty & Arasaratnam, 2012; Brodaty, Green, & Koschera, 2003; Olazarán et al., 2010; Van’t Leven et al., 2013). Studies also have found that a combination of physical exercise and an enriched environment induces more new neurons and benefits the brain greater than either exercise or an enriched environment alone (Fabel & Kempermann, 2008; Fabel et al., 2009; Olson, Eadie, Ernst, & Christie, 2006). It might be that the other intervention components, managing of behavioral problems and planning of pleasant activities, in combination with physical exercise, reinforced each other and enhanced attention. We therefore cannot be sure that a change in attention was due to the physical exercise component. Future research is needed to determine whether the effect we found on the attention of people with dementia is due to a combination of intervention components or to physical exercise or one of the other components only. However, the effect on attention should be interpreted with caution because of a small effect size (d = 0.25).

Executive Functioning

This study found no benefits of the multicomponent intervention on the EF domain. This contradicts previous findings of single and multicomponent interventions with physical exercise on EF in older people with MCI/mild dementia (Lautenschlager, Cox, & Kurz, 2010; van Uffelen et al., 2008) or people without cognitive impairment (Angevaren et al., 2008; Smith et al., 2010). Reviews in people with dementia showed that physical activity might have an effect on EF (Coelho, Santos-Galduroz, Gobbi, & Stella, 2009; Eggermont & Scherder, 2006; Hess et al., 2014; Heyn, Abreu, & Ottenbacher, 2004; Lautenschlager et al., 2010; Öhman et al., 2014), but it should be mentioned that most reviews included more studies with only people with mild dementia and residents instead of people with mild to moderate dementia living at home, like our present research population. Comparable studies for community-living people with moderate cognitive impairment are scarce. A long-term RCT examining the effects of walking on cognition in a group of community-living older people varying from MCI to severe dementia showed an effect on EF domain (measured by the key search test, digit span backward, two category fluency tests, visual memory span backward, Stroop task, and digit symbol substitution test) in people with MCI/mild dementia (MMSE ≥ 20) (Volkers, 2012). The walking concerned 30-min walks for 5 days a week. In the study of Volkers (2012), no effect of walking on EF was observed in people with moderate to severe cognitive impairment. Another comparable recent RCT, examining the effects of a regular, long-term physical exercise program (aerobic, strength, endurance, and balance exercises) performed by people with dementia at home for 1 hr twice a week for 12 months showed some positive effects on the EF of people with dementia, but the effects were mild, and participants had to exercise 12 months until positive results were observed on the clock drawing test (Öhman et al., 2016).

Memory

The multi-component dyadic intervention had no effect on memory in the current study. It is known that memory benefits less from physical exercise than EF (Colcombe & Kramer, 2003; Smith et al., 2010). In people with cognitive impairment, the prefrontal cortex and hippocampus are affected (Rosano et al., 2012). Physical exercise has more impact on the functioning of the prefrontal cortex (a brain area responsible for EF) than of the hippocampus (a brain area responsible for memory). The results of comparable studies examining regular physical exercise for community-living people with dementia also did not show any effect on memory (Öhman et al., 2016; Volkers, 2012).

Considerations

Randomization succeeded, showing that both groups were similar at baseline, and the dropout rates were reasonable for this vulnerable target group (< 30%) (Bell, Kenward, Fairclough, & Horton, 2013). Dyads experienced no adverse effects. Furthermore, because it is known that the medication use of people with dementia can influence cognitive functioning (Behl, Lanctot, Streiner, Guimont, & Black, 2006), we controlled for medication use: in the present study there was a very similar distribution in the use of cardiovascular medication (ATC-C) and antidementia medications (ATC-N06DA) among the groups.

Several factors may have had an impact on the results. In the Netherlands, for people with dementia living in the community, it is common to receive care in a daycare facility for 1 or more days, where they participate in staffed activities such as music and physical exercise programs. In our sample, half of the people with dementia received 1 or more days care in a daycare facility. On top of this usual care, we examined the effectiveness of this intensive intervention. This could have hampered measuring the possible intervention effects in case of improvement. In future studies, the impact of usual care provided in a specific country need to be taken into account when offering an additional intervention (Prick et al., 2014).

To improve both the prefrontal cortex (a brain area responsible for EF) and the hippocampus (a brain area responsible for EF) with physical exercise training, the physical exercise should be of enough intensity (Kramer, Colcombe, McAuley, Scalf, & Erickson, 2005). It could be that the physical exercise in the current intervention was not performed with sufficient intensity, duration, or frequency to find a significant effect on memory. A review, studying the effects of physical exercise on physical functioning and ADL performance in older people with dementia, showed the largest improvements for interventions with the highest intensity: interventions with a duration of minimal 12 weeks, a frequency of three times a week, with 45–60 min a session (Blankevoort et al., 2010), but the effect on cognitive functioning was not studied in this review. According to the protocol, the duration (minimal 12 weeks), frequency (3 times a week), and intensity (30 min instead of 45 min) of the present physical exercise component is almost in accordance with Blankevoort et al. (2010). However, physical exercise homework compliance was not performed as frequently as prescribed according protocol in the present study: 68% of the dyads exercised one to three times a week and 32% of the dyads did not do their physical exercise homework at all. In previous physical exercise trials in older people, adherence to schedules has been low (Forbes et al., 2013; Volkers, 2012). A recent systematic review outlined that the incorporation of regular physical exercise into daily routines benefits cognitive function in people with dementia, especially when implemented earlier in the disease process (Phillips, Baktir, Das, Lin, & Salehi, 2015). Another recent RCT, examining the effect of combined aerobic and strength training versus aerobic-only training in people with dementia, concluded that an alternating form of aerobic and strength training sessions was more effective than aerobic-only training in slowing cognitive decline in people with dementia (Bossers et al., 2015). We offered a combined aerobic and strength training in the present study, but during the 1-hr home visits, there was not enough time to practice aerobic exercises extensively, such as walking. Self-evidently, we stimulated the dyads to perform aerobic exercises with the goal of increasing the time for at least 20–30 min a day according protocol. Furthermore, introducing regular (aerobic) exercises in people who may not have been used to that in the past requires high levels of motivation. It is known that apathy in people with dementia is associated with a lack of motivation (Landes, Sperry, Strauss, & Geldmacher, 2001). More research is needed to determine how to enhance motivation in people with dementia and their caregivers to exercise regularly and maintain their adherence and to determine the right dose-response relationship between exercise and cognition in people with dementia.

Another consideration concerns that participation in a physical exercise program always takes place in the background of one’s own present and past level of physical exercise, which varied considerably between participants (Scherder et al., 2014; van Uffelen et al., 2008). Therefore, we monitored the past level of physical exercise in the childhood (< 18 years) and we monitored global information on the level of physical exercise during the study with logs maintained by the caregivers. In the present study some of the participants were already physically active and other participants less active. Therefore, the level of physical exercise may be a strong confounder and, therefore, we accounted for the past level of physical exercise in the analysis. In addition, compliance analyses for physical exercise were performed. However, for future studies, it is advisable to analyze the frequency, intensity, duration, and kind of physical exercises and activities per day during the study and in the past more precisely, instead of only at a global level and only for physical exercises.

Furthermore, determining the type and onset of dementia is problematic. Currently, the diagnosis of dementia is initiated mostly on a clinician’s suspicion based on symptoms of the person with dementia and caregivers’ concerns, usually in a primary care setting (Brayne, Fox, & Boustani, 2007). It is an indication because a definite diagnosis can only be confirmed at postmortem or through a brain biopsy. For this reason, subgroup analysis between the different types of dementia is debatable.

Finally, considerations concern the limited relevance of physical exercise within the multicomponent dyadic intervention and the inability to isolate and draw definitive conclusions on what aspects of the multicomponent dyadic intervention have affected attention. These unavoidable weaknesses are overweighed by the strengths of our study, which are: (1) the ecological validity of the RCT: the results of the process evaluation of the quality of the present RCT and intervention demonstrated a study design and intervention protocol meeting high research standards (Prick et al., 2014); (2) the special elderly population with dementia; (3) the relatively large sample of n = 111 dyads, which is a reasonable sample size in this field of geriatric research (Armijo-Olivo, Warren, & Magee, 2009); and (4) the presence of the 6-month follow-up.

Conclusion

In conclusion, this randomized controlled trial study of a multicomponent dyadic intervention with physical exercise showed no effects on the memory and EF of people with dementia; only a small significant effect of the intervention was found on a simple attention task. Since the effect on cognitive functioning in people with dementia was not studied for the original intervention as developed in the United States by Teri et al. (2003), no comparison can be made. Finding only a small significant effect might be explained by the ineffectiveness of the intervention, but also by moderate treatment adherence to the physical exercise and pleasant activities homework or a lack of room for improvement on the intended outcome measures because half of the people with dementia already received care in a daycare facility.

Acknowledgments

The authors would like to thank the participants and their caregivers for their time and goodwill participating in the study and we would like to thank all research assistants who contributed to the study. This study was funded by the Dutch Health Insurers Innovation Foundation. Trial registration: Dutch trial register: NTR1802, registration date May 6, 2009.

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Prick and Scherder are with the Department of Clinical, Neuro- & Developmental Psychology and the EMGO Institute for Health and Care Research, Faculty of Beahavioural and Movement Sciences, VU University, Amsterdam, The Netherlands. De Lange is with Research Centre Innovations in Care, Rotterdam University of Applied Sciences, Rotterdam, The Netherlands. Twisk is with the Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands. Pot is with the Department of Clinical, Neuro- & Developmental Psychology and the EMGO institute for Health and Care Research, Faculty of Beahavioural and Movement Sciences, VU University, Amsterdam, The Netherlands; Program on Aging, Institute on Mental Health and Addiction, Utrecht, The Netherlands; and School of Psychology, University of Queensland, St Lucia, QLD, Australia.

Address author correspondence to Anna-Eva Prickat a.j.c.prick@vu.nl.
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  • —Flow chart of the present study. CG = caregiver; PD = person with dementia; ITT = intension-to-treat analysis.

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