Effects of multidomain lifestyle intervention, omega-3 supplementation or their combination on physical activity levels in older adults: secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) randomised controlled trial

Effects of multidomain lifestyle intervention, omega-3 supplementation or their combination on... Abstract Background/objectives to investigate the effects of a 3-year multidomain lifestyle intervention, omega-3 supplementation or both on physical activity (PA) in older adults with subjective memory complaints. Design/settings/subjects the Multidomain Alzheimer Preventive Trial was a 3-year randomised controlled trial that enroled 1,680 community-dwelling adults aged 70 years or over, with subjective memory complaints. Participants were randomised to omega-3 supplementation (total daily dose of 800 mg docosahexanoic acid and up to 225 mg eicosapentanoic acid), multidomain intervention (nutritional and exercise counselling and cognitive training), omega-3 plus multidomain intervention or placebo with usual care. Methods PA was assessed using a self-reported questionnaire. From this, global moderate-to-vigorous PA, leisure-time PA, non-leisure-time PA and light PA were measured in metabolic equivalent tasks—minutes per week (MET-min/week). Results in the multidomain groups, participants significantly increased their moderate-to-vigorous and leisure-time PA at 6 months (≥300 MET-min/week for both in the multidomain groups; P ≤ 0.002) before returning to baseline by the end of the trial. Activity in the placebo/usual care and omega-3/usual care groups declined overtime. Between-group differences remained significant for both multidomain groups for leisure-time physical activity at 2- and 3-year follow-ups. Compared to placebo/usual care, interventions had no significant effects on non-leisure-time PA and light PA. Omega-3 supplementation alone had no effects on PA. Conclusions a multidomain intervention focused on cognitive training, and nutritional and PA counselling increased PA in the short-term and limited its decline in the long-term among older adults with memory complaints. ClinicalTrials.gov—Registration number: NCT0067268 physical activity, older people, cognitive decline Introduction Low level of physical activity (PA) is an important life-threatening modifiable risk factor [1], costing to the healthcare systems 53.8 billion (international $) in the globe for the year 2013 [2]. Nonetheless, the prevalence of low PA is very high [1], particularly among older people, suggesting that interventions capable of increasing PA levels are urgently needed. Randomised controlled trials (RCT) have already investigated the effects of PA counselling on PA levels in older people [3–7]. However, intervention length has been short (<12 months) and focused specifically on PA counselling. The effects of comprehensive multidomain lifestyle interventions, with PA, diet and cognitive training, has been poorly investigated; indeed, beside PA counselling, dietary changes and cognitive training might improve PA through indirect mechanisms, such as improved muscle function (e.g. optimising protein consumption in order to avoid sarcopenia) and executive function (which was found to be bidirectionally associated to PA) [8]. To the best of our knowledge, the only two long-term RCTs [9, 10] among older adults at-risk for cognitive decline that operationalised multidomain interventions found mixed results regarding the effects of the interventions on PA. Therefore, the potential role of multidomain lifestyle interventions for promoting PA in people at-risk for cognitive decline remains unknown. Furthermore, in older adults, PA may decrease as a consequence of reductions in muscle mass and function. Since supplementation of omega-3 poly-unsaturated fatty acids (PUFA) may improve muscle strength and function [11–13], and given the link between muscle health and PA for older adults [14], it is possible that omega-3 PUFA could increase PA levels in older people. This paper presents data from the MAPT trial, in which the primary outcome was cognitive decline; no beneficial effects were seen either from the multidomain intervention or polyunsaturated fatty acids, either alone or in combination [15,16]. The objective of this study was to determine the effects of a 3-year multidomain lifestyle intervention, omega-3 supplementation, or both on the secondary outcomes of PA volumes and levels in a population of older adults with subjective memory complaints. We hypothesised that multidomain interventions (both alone and combined with omega-3 supplementation) would increase overall PA, particularly PA performed during leisure time. Methods This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) (registration: NCT00672685) [15, 16], a 3-year randomised controlled trial (RCT) that tested the effects of omega-3, multidomain intervention involving nutritional and exercise counselling and cognitive training, or their combination against placebo/usual care on cognitive function [16]. All MAPT participants signed an informed consent and the study protocol was approved by the French Ethical Committee located in Toulouse (CPP SOOM II). A full description of the present study methods is available in the supplementary data available at Age and Ageing online. Participants Dementia-free community-dwelling people aged ≥70 and meeting one or more of the following criteria: spontaneous memory complaints, limitation in executing ≥1 Instrumental Activity of Daily Living, or slow gait speed (<0.8 m/s). From the 1,680 participants randomised, one person withdrew from the study. Randomisation and masking Participants were randomised in a 1:1:1:1 ratio using centre-stratified computer-generated randomisation procedures. Group allocation concealment was guaranteed. The research team and participants were blinded to PUFA/placebo assignment. Outcome assessors were blinded to group allocation. Interventions Multidomain The multidomain encompassed three interventions: cognitive training, nutrition counselling and PA counselling. Group-based multidomain intervention, 2-h per session, were performed twice a week during the first 4 weeks, and once a week for the following 4 weeks. The content of the sessions were: 1 h of cognitive training (memory and reasoning), 15 min of nutritional advice, and 45 min of PA counselling. For PA counselling, a PA instructor provided advices about the health benefits associated to PA and encouraged participants to meet current public health guidelines on PA for older people, i.e. 30 min PA/day, 5 days/week [17]. An individualised exercise program was elaborated and each participant was stimulated to perform the home-based exercises from his/her program. For the remaining time of the intervention period (from months 3 to 36), participants received a 1-h session per month to reinforce the key messages related to all three domains. Two 2-h sessions were organised at 12 and 24 months to boost the effects of the intervention. A preventive consultation for the management of cardiovascular risk factors and the detection of functional deficits was performed by a physician at baseline, 1 and 2 years. Omega-3 PUFA supplementation Participants took two capsules per day during 36 months of a mixture containing natural fish oil with a minimum of 65% docosahexaenoic acid (DHA) and a maximum of 15% eicosapentaenoic acid (EPA) (total daily dose of 800 mg DHA and up to 225 mg EPA). Multidomain plus omega-3 Participants received both multidomain and omega-3 supplementation during 36 months. Placebo/usual care During 36 months, people took placebo capsules containing flavoured paraffin oil. Capsules were of similar appearance and taste to the active supplement. No lifestyle interventions were provided to participants in this group. Outcomes PA was assessed at baseline, and 6-, 12-, 24- and 36-month time points [18]. PA data were collected using a self-reported questionnaire informing the frequency and time people spent in leisure time (walking for exercise), gardening-related (e.g. mowing the lawn) and household activities (e.g. moderate household chore). PA variables were computed in metabolic equivalent task [19] (MET)-minutes per week (continuous variables). The MET-min/week for all moderate-to-vigorous PAs (MVPAs) were summed providing a continuous measure of global PA. Continuous domain-specific PA variables were also created for moderate-to-vigorous leisure-time physical activity (LTPA) and non-LTPA, i.e. the addition of household PA and gardening-related activities. Light PA was calculated by adding the MET-min/week of PAs with MET values <3. On the basis of overall MVPA, participants were grouped into six PA levels (ordinal variable), from inactive to very high. Those doing ≥600 MET-min/week of MVPA were considered as meeting the minimum recommended PA [17]. Adherence Adherence to omega-3 PUFA supplementation, placebo and multidomain sessions were assessed. For multidomain interventions, adherence was sub-divided into three different phases: adoption (first 2 months, corresponding to the intensive part of the intervention), transition (months 3–6) and maintenance (from month 7 onwards). People receiving ≥75% of the intervention prescribed were classified as adherent. Statistical analysis Descriptive statistics were presented as means (SD) or median (interquartile range—IQR) for continuous variables and absolute numbers and percentages for categorical variables. One-way ANOVA or the Kruskall–Wallis test and the chi-square test were used to examine differences across study groups at baseline, as appropriate. Mixed-effect linear regressions and mixed-effect ordered logistic regression (with a random effect at the participant’s level) were performed on the continuous PA variables (MVPA, LTPA, non-LTPA and light PA) and ordinal PA variable (PA levels), respectively. In all models, fixed effects were time (categorical variable), group and group-by-time interaction. Adjusted means for each group were obtained from the models and adjusted mean differences (against the placebo/usual care group) were calculated. Spearman rank correlations were used to examine the relationships of adherence to the multidomain intervention with score changes in MVPA and LTPA. Statistical significance was determined by a P < 0.05. Analyses followed the ITT principle and were performed with Stata (v.14.0, Texas, USA) statistical software. Exploratory analysis We performed several exploratory mixed-effect linear regressions on MVPA and LTPA. First, since executive function is associated to PA changes [8], we adjusted analyses for baseline executive function (as assessed by the Controlled Oral Word Association Test) [20]. Second, because the “induction phase” (i.e. 12 first sessions) was the heart of the MAPT multidomain intervention, a perprotocol population was defined for the present work as people who attended two or more sessions during this study phase. Analyses were ran to investigate the effects of the interventions in the whole perprotocol population, in adherents (≥75%) and non-adherents (<75%) to the 3-year period of the multidomain intervention, and according with participation in the two “boost sessions” (attendance to both sessions: yes or no) performed at 12- and 24-month follow-ups. Analyses stratified for the baseline values of the clinical dementia rating (CDR = 0 or CDR = 0.5) were also performed (both ITT and perprotocol populations). Results Table 1 shows the characteristics of the 1,679 participants. Groups did not differ at baseline. Around 70% of participants met the minimum recommended PA. Attendance to the multidomain intervention across the 3-year period was high (median 76.7%, IQR [41.9–88.4%]), but declined overtime from the adoption phase (first 2 months, 12 sessions: 91.7% [66.7–100%]), through the transition (months 3–6, once per month: 75% [50–100%]) and maintenance (months 7–36, once per month: 70.4% [18.5–85.2%]) phases; in the last year of the trial, more than 30% (n = 260) of participants had dropped out (adherence 66.6% [0–88.9%]). 429 (51.1%) people receiving the multidomain intervention adhered to ≥75% of the sessions and 732 (87.3%) attended to at least 2 sessions during the first 2 months of the trial (perprotocol population). Adherence to omega-3 and placebo during the trial were 81% (SD: 26.2%) and 82% (SD: 25.8%), respectively. Table 1. Baseline characteristics of the 1,679 study participants and differences among groupsa Variables  Multidomain + Omega-3 (n = 417)  Omega-3 (n = 422)  Multidomain (n = 420)  Placebo/usual care (n = 420)  Age, y  76 (4.4)  76.1 (4.7)  75.5 (4.2)  75.6 (4.4)  Women, n (%)  263 (63.1)  269 (63.7)  276 (65.7)  279 (66.4)  Education, n (%)   No diploma or primary school certificate  88 (21.3)  107 (26.6)  87 (21)  89 (21.6)   Secondary education  156 (37.7)  128 (31.8)  134 (32.3)  135 (32.8)   High-school diploma  56 (13.5)  51 (12.7)  64 (15.4)  71 (17.2)   University level  114 (27.5)  116 (28.9)  130 (31.3)  117 (28.4)  Mini mental state examination (0–30)  28.1 (1.6)  28.1 (1.6)  28 (1.6)  28.1 (1.5)  Clinical dementia rating, n (%) of 0.5  170 (40.8)  181 (43)  177 (42.1)  178 (42.4)  Geriatric depression scale (0–15)  3.2 (2.5)  3.3 (2.6)  3.3 (2.6)  3.3 (2.7)  Usual gait speed (m/s)  1.09 (0.3)  1.08 (0.2)  1.08 (0.3)  1.10 (0.3)  Short physical performance battery (0–12)  10.5 (1.8)  10.5 (1.5)  10.6 (1.7)  10.6 (1.6)  Body mass index (kg/m2)  26.2 (4.3)  26.3 (4.1)  26 (4)  26 (3.9)  MVPA (MET-min/week)b  1,017 (449–1,992)  1,113 (466–2,164)  1,146 (513–1,962)  1,131 (517–2,088)  LTPA (MET-min/week)b  681 (172–1,413)  774 (193–1,548)  774 (193–,523)  774 (258–1,659)  Housework + gardening PA (MET-min/week)b  157 (0–420)  105 (0–490)  137 (0–446)  105 (0–420)  Light PA (MET-min/week)b  0 (0–172)  0 (0–210)  0 (0–247)  0 (0–138)  PA levels, n (%)   Inactive  36 (8.6)  34 (8.1)  34 (8.1)  28 (6.7)   Very low active  42 (10.1)  44 (10.4)  41 (9.8)  40 (9.5)   Low active  58 (13.9)  41 (9.7)  42 (10)  54 (12.9)   Moderately active  47 (11.3)  51 (12.1)  48 (11.4)  54 (12.9)   High active  47 (11.3)  49 (11.6)  50 (11.9)  42 (10)   Very high active  187 (44.8)  203 (48.1)  205 (48.8)  202 (48.1)  Variables  Multidomain + Omega-3 (n = 417)  Omega-3 (n = 422)  Multidomain (n = 420)  Placebo/usual care (n = 420)  Age, y  76 (4.4)  76.1 (4.7)  75.5 (4.2)  75.6 (4.4)  Women, n (%)  263 (63.1)  269 (63.7)  276 (65.7)  279 (66.4)  Education, n (%)   No diploma or primary school certificate  88 (21.3)  107 (26.6)  87 (21)  89 (21.6)   Secondary education  156 (37.7)  128 (31.8)  134 (32.3)  135 (32.8)   High-school diploma  56 (13.5)  51 (12.7)  64 (15.4)  71 (17.2)   University level  114 (27.5)  116 (28.9)  130 (31.3)  117 (28.4)  Mini mental state examination (0–30)  28.1 (1.6)  28.1 (1.6)  28 (1.6)  28.1 (1.5)  Clinical dementia rating, n (%) of 0.5  170 (40.8)  181 (43)  177 (42.1)  178 (42.4)  Geriatric depression scale (0–15)  3.2 (2.5)  3.3 (2.6)  3.3 (2.6)  3.3 (2.7)  Usual gait speed (m/s)  1.09 (0.3)  1.08 (0.2)  1.08 (0.3)  1.10 (0.3)  Short physical performance battery (0–12)  10.5 (1.8)  10.5 (1.5)  10.6 (1.7)  10.6 (1.6)  Body mass index (kg/m2)  26.2 (4.3)  26.3 (4.1)  26 (4)  26 (3.9)  MVPA (MET-min/week)b  1,017 (449–1,992)  1,113 (466–2,164)  1,146 (513–1,962)  1,131 (517–2,088)  LTPA (MET-min/week)b  681 (172–1,413)  774 (193–1,548)  774 (193–,523)  774 (258–1,659)  Housework + gardening PA (MET-min/week)b  157 (0–420)  105 (0–490)  137 (0–446)  105 (0–420)  Light PA (MET-min/week)b  0 (0–172)  0 (0–210)  0 (0–247)  0 (0–138)  PA levels, n (%)   Inactive  36 (8.6)  34 (8.1)  34 (8.1)  28 (6.7)   Very low active  42 (10.1)  44 (10.4)  41 (9.8)  40 (9.5)   Low active  58 (13.9)  41 (9.7)  42 (10)  54 (12.9)   Moderately active  47 (11.3)  51 (12.1)  48 (11.4)  54 (12.9)   High active  47 (11.3)  49 (11.6)  50 (11.9)  42 (10)   Very high active  187 (44.8)  203 (48.1)  205 (48.8)  202 (48.1)  aValues are means (SD) for continuous and ordinal variables and absolute numbers (%) for categorical variables, unless otherwise stated. bValues are median (interquartile range). Table 2 shows the results of the mixed-effect linear regressions on PA continuous variables. The two multidomain groups increased their MVPA and LTPA at 6 months, followed by a decline until the end of the trial, getting back to their baseline PA values. The placebo/usual care and omega-3 alone groups declined from baseline to trial end, with within-group differences being significant at 2- (for LTPA) and 3-year (for MVPA and LTPA) follow-ups for both groups (see Figures S1 and S2 in the supplementary data available at Age and Ageing online). Compared to placebo/usual care, the multidomain plus omega-3 group had significantly higher MVPA at 6-month and higher LTPA at 6-month, 2- and 3-year follow-ups; whereas the multidomain alone had higher MVPA and LTPA at 6-month, 2- and 3-year follow-ups. Similar between-group differences were found regarding PA levels (Table S2 in the supplementary data available at Age and Ageing online). No differences were found for non-LTPA and light PA. Adherence to the multidomain intervention (Table S1 in the supplementary data available at Age and Ageing online) was not correlated with MVPA and LTPA change scores. Table 2. Effects of MAPT interventions on the different PA continuous outcomesa Outcomes  Multidomain + Omega-3  Multidomain  Omega-3  Placebo/usual care  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  MVPA   6 months  339 (107; 0.002)  449 (151; 0.003)  337 (106; 0.001)  447 (150; 0.003)  94 (107; 0.38)  203 (151; 0.18)  −110 (106; 0.30)     1 year  30 (109; 0.78)  61 (154; 0.69)  83 (109; 0.45)  113 (154; 0.46)  −18 (110; 0.87)  13 (155; 0.93)  −30 (109; 0.78)     2 years  60 (112; 0.59)  245 (158; 0.12)  168 (111; 0.13)  354 (157; 0.02)  −75 (112; 0.50)  110 (158; 0.48)  −185 (111; 0.09)     3 years  −33 (112; 0.77)  304 (159; 0.055)  90 (112; 0.42)  428 (158; 0.007)  −316 (112; 0.005)  21 (159; 0.89)  −337 (112; 0.003)    LTPA   6 months  300 (74; <0.001)  420 (104; <0.001)  326 (75; <0.001)  446 (103; <0.001)  48 (73; 0.51)  168 (104; 0.10)  −120 (73; 0.10)     1 year  74 (75; 0.33)  117 (106; 0.27)  62 (75; 0.40)  106 (106; 0.32)  −94 (75; 0.21)  −50 (106; 0.64)  −44 (75; 0.56)     2 years  83 (77; 0.28)  235 (108; 0.03)  95 (76; 0.21)  247 (108;0.02)  −171 (77; 0.03)  −19 (109; 0.86)  −152 (76; 0.047)     3 years  70 (77; 0.36)  316 (109; 0.004)  27 (77; 0.72)  273 (109; 0.01)  −241 (77; 0.002)  4 (109; 0.97)  −245 (77; 0.001)    Housework + gardening   6 months  41 (78; 0.60)  31 (110; 0.78)  16 (77; 0.83)  6 (109; 0.96)  49 (78; 0.53)  39 (110; 0.72)  10 (78; 0.89)     1 year  −38 (79; 0.63)  −27 (112; 0.81)  15 (79; 0.85)  26 (112; 0.81)  83 (80; 0.30)  94 (113; 0.40)  −11 (79; 0.89)     2 years  −21 (81; 0.79)  9 (115; 0.94)  68 (81; 0.40)  98 (114; 0.39)  91 (82; 0.26)  122 (115; 0.29)  −30 (81; 0.71)     3 years  −94 (82; 0.25)  −8 (115; 0.94)  68 (82; 0.41)  154 (115; 0.18)  −73 (82; 0.37)  14 (115; 0.90)  −87 (81; 0.29)    Light PA   6 months  129 (57; 0.02)  105 (80; 0.19)  21 (56; 0.71)  −4 (80; 0.96)  18 (57; 0.75)  −6 (80; 0.94)  25 (57; 0.66)     1 year  36 (58; 0.53)  97 (82; 0.24)  84 (58; 0.15)  114 (82; 0.08)  45 (58; 0.44)  106 (82; 0.20)  −60 (58; 0.29)     2 years  −7 (60; 0.90)  35 (84; 0.68)  −24 (59; 0.68)  18 (83; 0.83)  −4 (60; 0.95)  38 (84; 0.65)  −42 (59; 0.48)     3 years  −28 (60; 0.64)  44 (83; 0.60)  −104 (60; 0.08)  −32 (84; 0.70)  −49 (60; 0.41)  23 (84; 0.79)  −72 (59; 0.23)    Outcomes  Multidomain + Omega-3  Multidomain  Omega-3  Placebo/usual care  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  MVPA   6 months  339 (107; 0.002)  449 (151; 0.003)  337 (106; 0.001)  447 (150; 0.003)  94 (107; 0.38)  203 (151; 0.18)  −110 (106; 0.30)     1 year  30 (109; 0.78)  61 (154; 0.69)  83 (109; 0.45)  113 (154; 0.46)  −18 (110; 0.87)  13 (155; 0.93)  −30 (109; 0.78)     2 years  60 (112; 0.59)  245 (158; 0.12)  168 (111; 0.13)  354 (157; 0.02)  −75 (112; 0.50)  110 (158; 0.48)  −185 (111; 0.09)     3 years  −33 (112; 0.77)  304 (159; 0.055)  90 (112; 0.42)  428 (158; 0.007)  −316 (112; 0.005)  21 (159; 0.89)  −337 (112; 0.003)    LTPA   6 months  300 (74; <0.001)  420 (104; <0.001)  326 (75; <0.001)  446 (103; <0.001)  48 (73; 0.51)  168 (104; 0.10)  −120 (73; 0.10)     1 year  74 (75; 0.33)  117 (106; 0.27)  62 (75; 0.40)  106 (106; 0.32)  −94 (75; 0.21)  −50 (106; 0.64)  −44 (75; 0.56)     2 years  83 (77; 0.28)  235 (108; 0.03)  95 (76; 0.21)  247 (108;0.02)  −171 (77; 0.03)  −19 (109; 0.86)  −152 (76; 0.047)     3 years  70 (77; 0.36)  316 (109; 0.004)  27 (77; 0.72)  273 (109; 0.01)  −241 (77; 0.002)  4 (109; 0.97)  −245 (77; 0.001)    Housework + gardening   6 months  41 (78; 0.60)  31 (110; 0.78)  16 (77; 0.83)  6 (109; 0.96)  49 (78; 0.53)  39 (110; 0.72)  10 (78; 0.89)     1 year  −38 (79; 0.63)  −27 (112; 0.81)  15 (79; 0.85)  26 (112; 0.81)  83 (80; 0.30)  94 (113; 0.40)  −11 (79; 0.89)     2 years  −21 (81; 0.79)  9 (115; 0.94)  68 (81; 0.40)  98 (114; 0.39)  91 (82; 0.26)  122 (115; 0.29)  −30 (81; 0.71)     3 years  −94 (82; 0.25)  −8 (115; 0.94)  68 (82; 0.41)  154 (115; 0.18)  −73 (82; 0.37)  14 (115; 0.90)  −87 (81; 0.29)    Light PA   6 months  129 (57; 0.02)  105 (80; 0.19)  21 (56; 0.71)  −4 (80; 0.96)  18 (57; 0.75)  −6 (80; 0.94)  25 (57; 0.66)     1 year  36 (58; 0.53)  97 (82; 0.24)  84 (58; 0.15)  114 (82; 0.08)  45 (58; 0.44)  106 (82; 0.20)  −60 (58; 0.29)     2 years  −7 (60; 0.90)  35 (84; 0.68)  −24 (59; 0.68)  18 (83; 0.83)  −4 (60; 0.95)  38 (84; 0.65)  −42 (59; 0.48)     3 years  −28 (60; 0.64)  44 (83; 0.60)  −104 (60; 0.08)  −32 (84; 0.70)  −49 (60; 0.41)  23 (84; 0.79)  −72 (59; 0.23)    Note:SE, standard error. aAll PA outcomes are measured in MET-min/week. bComparisons are performed against the reference category group “Placebo/usual care”. Positive values indicates better PA in the intervention group compared to placebo/usual care, while negative values indicate better PA in the placebo/usual care group compared to intervention groups. cPositive values indicate increasing PA overtime. Exploratory analysis (see Tables S3–S5 in the supplementary data available at Age and Ageing online) adjusted for executive function provided similar results. Analysis using the perprotocol population gave unchanged findings. For non-adherent participants, although they have increased their LTPA at 6 months, they did not differ from placebo/usual care in the other time points. Results were similar for participants who attended and those who did not the two boost sessions. Similar results were also obtained regardless of participants’ cognitive status (CDR 0 and CDR 0.5) for both ITT and perprotocol populations, even though multidomain intervention’s positive effects have been slightly more pronounced among CDR 0.5. For all exploratory analyses, changes in MVPA and LTPA in the omega-3 PUFA alone group did not differ from those in the placebo/usual care. Discussion This work showed that a multidomain intervention focused on cognitive training, and nutritional and PA counselling increased the volumes (MVPA and LTPA) and levels of PA in the short-term (6-month follow-up) and limited their decline in the long-term (2- and 3-year follow-ups) among older adults with memory complaints, even among those with objective cognitive decline (CDR 0.5). Omega-3 PUFA supplementation had no effect on PA. In the only two RCTs employing multidomain interventions in an older population at-risk of cognitive decline, one study [9] used an intensive proof-of-concept intervention composed of several in-person sessions for the different components of the multidomain intervention, including supervised exercise training performed up to 5 times a week over 2 years; Ngandu and colleagues [9] found this intensive intervention increased the percentage of people doing PA at least twice a week. The other RCT [10] used individually tailored lifestyle advices (risk factors, including PA, were assessed at each visit) performed after each 4-month study visit over 6 years; this trial found the lifestyle intervention was ineffective to increase the number of participants meeting public health guidelines on PA [17]. Therefore, our findings add important information to this topic since this is the first study showing that a simple (not too much time-consuming), long-term multidomain intervention was able to improve PA behaviour among older adults with memory complaints, including those with objective cognitive decline. Moreover, our findings were independent of participants’ executive functioning, which was found to be an important predictor of PA in older adults [8, 21]. The multidomain intervention impacted only LTPA and MVPA, confirming our initial hypothesis. This is an important finding since MVPA and LTPA were found to be associated with good health outcomes [22–31]. The between-group differences for LTPA at the 6-month and 3-year follow-ups roughly corresponded to more than 100 min/week and 70 min/week, respectively, of brisk walking supplementary performed by the multidomain groups compared to placebo/usual care; these amounts of supplementary PA are clinically relevant outcomes. Indeed, data from six large longitudinal cohorts (n = 654,827) [22] have shown that doing less than 75 min/week of brisk walking was associated with a reduced risk of mortality by 19%. As a note of caution, MAPT population already had very high PA levels at baseline; the between-group differences found in this study might probably be less clinically relevant than if they had been found among sedentary individuals. As hypothesised, the effects of multidomain interventions were more pronounced in the first 6 months of the study probably because this corresponded to the most intensive period of the intervention. Although after the initial increase both multidomain groups have declined on PA, their PA values at 3 years were similar to their baseline values, whereas PA values in the non-multidomain groups declined consistently throughout the trial. Moreover, between-group differences remained significant at the study’s end, particularly among participants with attendance rates 75% or over, suggesting that high adherence played a role in the overtime sustainability of the multidomain intervention effects. This is a relevant information since we observed a decline in adherence rates for the multidomain intervention over the 3-year period, suggesting that finding out how to motivate people to participate even in simple, non-invasive and non-time-consuming interventions remains a major challenge in older populations. Regarding omega-3, previous trials, but not all [32], have found omega-3 PUFA supplementation increased muscle mass, function [11–13], and adaptive response to training (particularly among women) [33] in older adults. However, we failed to show an effect of omega-3 PUFA on PA, probably because PA is a multidimensional behaviour [34, 35]. Further research investigating the effects of omega-3 on both PA, physical capacity (e.g. maximal oxygen uptake (VO2max), which is less likely to be influenced by external factors than PA), and muscle function may provide complementary information to this field. The main strengths of this study are its RCT design, the large sample size, the long-term intervention period, good adherence rates, and the several time-point assessments that allowed us to obtain precise trajectories of PA overtime. However, limitations are worth mentioning: the study population was globally fit, with very high PA levels. Therefore, our findings may not apply to more vulnerable older adult populations; PA was assessed through a self-reported questionnaire, which may have reduced data accuracy. Future large-scale interventions should make efforts to include both subjective and objective PA measures; precise measures of muscle function and physical capacity were lacking; finally, it was impossible to disentangle the individual contribution of each component of the multidomain intervention. Although nutritional advice (particularly, through improved protein consumption) and cognitive stimulation may indirectly influence PA, we were unable to determine if such a multidomain approach leads to better results on PA than an intervention focusing solely on PA advices; this is particularly relevant under a cost-effectiveness perspective and should be addressed in future studies. In sum, we found that a multidomain intervention (cognitive training, and nutritional and PA advices) increased/maintained PA among older adults at-risk for cognitive decline over a 3-year period. Investigating if the effects of the intervention remain during the post-intervention period would inform on the long-term effectiveness of the approach. An observational longitudinal study examining the mediation role of changes in muscle function, physical capacity, and psychosocial variables (e.g. self-efficacy, social support) for improving PA levels in older populations would bring about valuable information to understand the mechanisms leading to sustained high PA in advanced ages. Key points Multidomain lifestyle intervention increased global and leisure-time moderate-to-vigorous PA in the short-term in people ≥70 years. The multidomain lifestyle intervention limited the decline of global and leisure-time PA in the long-term. Leisure-time PA increased to more than 100 min/week of brisk walking at 6 months and 70 min/week at 3 years. Supplementary data Supplementary data mentioned in the text are available to subscribers in Age and Ageing online. Authors’ contributions P.S.B. performed the statistical analysis, interpreted the data, drafted the article and approved the final version. Y.R. interpreted data, revised the article critically for important intellectual content and approved the final version. M.C. interpreted data, revised the article critically for important intellectual content and approved the final version. C.D. interpreted data, revised the article critically for important intellectual content and approved the final version. S.A. conceived the protocol and designed the whole MAPT trial, interpreted the data, revised the article critically for important intellectual content and approved the final version. B.V. conceived the protocol and designed the whole MAPT trial, interpreted the data, revised the article critically for important intellectual content and approved the final version. Conflict of interest None. Funding The MAPT study was supported by grants from the Gérontopôle of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the omega-3 supplement), Exhonit Therapeutics SA, Avid Radiopharmaceuticals Inc and in part by a grant from the French National Agency for Research called “Investissements d’Avenir” n°ANR-11-LABX-0018-01. The promotion of this study was supported by the University Hospital Center of Toulouse. The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d’Alzheimer (AMPA) and the UMR 1027 Unit INSERM-University of Toulouse III. The sponsor did not have a role in the study. References 1 GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. 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Google Scholar CrossRef Search ADS PubMed  32 Krzymińska-Siemaszko R, Czepulis N, Lewandowicz M et al.  . The effect of a 12-week omega-3 supplementation on body composition, muscle strength and physical performance in elderly individuals with decreased muscle mass. Int J Environ Res Public Health  2015; 12: 10558– 74. Google Scholar CrossRef Search ADS PubMed  33 Da Boit M, Sibson R, Sivasubramaniam S et al.  . Sex differences in the effect of fish oil supplementation on the adaptive response to resistance exercise training in older people: a randomized control trial. Am J Clin Nutr  2017; 105: 151– 8. Google Scholar CrossRef Search ADS PubMed  34 Olanrewaju O, Kelly S, Cowan A, Brayne C, Lafortune L. Physical activity in community dwelling older people: a systematic review of reviews of interventions and context. PLoS One  2016; 11: e0168614. Google Scholar CrossRef Search ADS PubMed  35 Rhodes RE, Quinlan A. Predictors of physical activity change among adults using observational designs. Sports Med  2015; 45: 423– 41. Google Scholar CrossRef Search ADS PubMed  Author notes †Description of MAPT/DSA Groups can be found in the online supplementary data. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Age and Ageing Oxford University Press

Effects of multidomain lifestyle intervention, omega-3 supplementation or their combination on physical activity levels in older adults: secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) randomised controlled trial

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© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com
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Abstract

Abstract Background/objectives to investigate the effects of a 3-year multidomain lifestyle intervention, omega-3 supplementation or both on physical activity (PA) in older adults with subjective memory complaints. Design/settings/subjects the Multidomain Alzheimer Preventive Trial was a 3-year randomised controlled trial that enroled 1,680 community-dwelling adults aged 70 years or over, with subjective memory complaints. Participants were randomised to omega-3 supplementation (total daily dose of 800 mg docosahexanoic acid and up to 225 mg eicosapentanoic acid), multidomain intervention (nutritional and exercise counselling and cognitive training), omega-3 plus multidomain intervention or placebo with usual care. Methods PA was assessed using a self-reported questionnaire. From this, global moderate-to-vigorous PA, leisure-time PA, non-leisure-time PA and light PA were measured in metabolic equivalent tasks—minutes per week (MET-min/week). Results in the multidomain groups, participants significantly increased their moderate-to-vigorous and leisure-time PA at 6 months (≥300 MET-min/week for both in the multidomain groups; P ≤ 0.002) before returning to baseline by the end of the trial. Activity in the placebo/usual care and omega-3/usual care groups declined overtime. Between-group differences remained significant for both multidomain groups for leisure-time physical activity at 2- and 3-year follow-ups. Compared to placebo/usual care, interventions had no significant effects on non-leisure-time PA and light PA. Omega-3 supplementation alone had no effects on PA. Conclusions a multidomain intervention focused on cognitive training, and nutritional and PA counselling increased PA in the short-term and limited its decline in the long-term among older adults with memory complaints. ClinicalTrials.gov—Registration number: NCT0067268 physical activity, older people, cognitive decline Introduction Low level of physical activity (PA) is an important life-threatening modifiable risk factor [1], costing to the healthcare systems 53.8 billion (international $) in the globe for the year 2013 [2]. Nonetheless, the prevalence of low PA is very high [1], particularly among older people, suggesting that interventions capable of increasing PA levels are urgently needed. Randomised controlled trials (RCT) have already investigated the effects of PA counselling on PA levels in older people [3–7]. However, intervention length has been short (<12 months) and focused specifically on PA counselling. The effects of comprehensive multidomain lifestyle interventions, with PA, diet and cognitive training, has been poorly investigated; indeed, beside PA counselling, dietary changes and cognitive training might improve PA through indirect mechanisms, such as improved muscle function (e.g. optimising protein consumption in order to avoid sarcopenia) and executive function (which was found to be bidirectionally associated to PA) [8]. To the best of our knowledge, the only two long-term RCTs [9, 10] among older adults at-risk for cognitive decline that operationalised multidomain interventions found mixed results regarding the effects of the interventions on PA. Therefore, the potential role of multidomain lifestyle interventions for promoting PA in people at-risk for cognitive decline remains unknown. Furthermore, in older adults, PA may decrease as a consequence of reductions in muscle mass and function. Since supplementation of omega-3 poly-unsaturated fatty acids (PUFA) may improve muscle strength and function [11–13], and given the link between muscle health and PA for older adults [14], it is possible that omega-3 PUFA could increase PA levels in older people. This paper presents data from the MAPT trial, in which the primary outcome was cognitive decline; no beneficial effects were seen either from the multidomain intervention or polyunsaturated fatty acids, either alone or in combination [15,16]. The objective of this study was to determine the effects of a 3-year multidomain lifestyle intervention, omega-3 supplementation, or both on the secondary outcomes of PA volumes and levels in a population of older adults with subjective memory complaints. We hypothesised that multidomain interventions (both alone and combined with omega-3 supplementation) would increase overall PA, particularly PA performed during leisure time. Methods This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) (registration: NCT00672685) [15, 16], a 3-year randomised controlled trial (RCT) that tested the effects of omega-3, multidomain intervention involving nutritional and exercise counselling and cognitive training, or their combination against placebo/usual care on cognitive function [16]. All MAPT participants signed an informed consent and the study protocol was approved by the French Ethical Committee located in Toulouse (CPP SOOM II). A full description of the present study methods is available in the supplementary data available at Age and Ageing online. Participants Dementia-free community-dwelling people aged ≥70 and meeting one or more of the following criteria: spontaneous memory complaints, limitation in executing ≥1 Instrumental Activity of Daily Living, or slow gait speed (<0.8 m/s). From the 1,680 participants randomised, one person withdrew from the study. Randomisation and masking Participants were randomised in a 1:1:1:1 ratio using centre-stratified computer-generated randomisation procedures. Group allocation concealment was guaranteed. The research team and participants were blinded to PUFA/placebo assignment. Outcome assessors were blinded to group allocation. Interventions Multidomain The multidomain encompassed three interventions: cognitive training, nutrition counselling and PA counselling. Group-based multidomain intervention, 2-h per session, were performed twice a week during the first 4 weeks, and once a week for the following 4 weeks. The content of the sessions were: 1 h of cognitive training (memory and reasoning), 15 min of nutritional advice, and 45 min of PA counselling. For PA counselling, a PA instructor provided advices about the health benefits associated to PA and encouraged participants to meet current public health guidelines on PA for older people, i.e. 30 min PA/day, 5 days/week [17]. An individualised exercise program was elaborated and each participant was stimulated to perform the home-based exercises from his/her program. For the remaining time of the intervention period (from months 3 to 36), participants received a 1-h session per month to reinforce the key messages related to all three domains. Two 2-h sessions were organised at 12 and 24 months to boost the effects of the intervention. A preventive consultation for the management of cardiovascular risk factors and the detection of functional deficits was performed by a physician at baseline, 1 and 2 years. Omega-3 PUFA supplementation Participants took two capsules per day during 36 months of a mixture containing natural fish oil with a minimum of 65% docosahexaenoic acid (DHA) and a maximum of 15% eicosapentaenoic acid (EPA) (total daily dose of 800 mg DHA and up to 225 mg EPA). Multidomain plus omega-3 Participants received both multidomain and omega-3 supplementation during 36 months. Placebo/usual care During 36 months, people took placebo capsules containing flavoured paraffin oil. Capsules were of similar appearance and taste to the active supplement. No lifestyle interventions were provided to participants in this group. Outcomes PA was assessed at baseline, and 6-, 12-, 24- and 36-month time points [18]. PA data were collected using a self-reported questionnaire informing the frequency and time people spent in leisure time (walking for exercise), gardening-related (e.g. mowing the lawn) and household activities (e.g. moderate household chore). PA variables were computed in metabolic equivalent task [19] (MET)-minutes per week (continuous variables). The MET-min/week for all moderate-to-vigorous PAs (MVPAs) were summed providing a continuous measure of global PA. Continuous domain-specific PA variables were also created for moderate-to-vigorous leisure-time physical activity (LTPA) and non-LTPA, i.e. the addition of household PA and gardening-related activities. Light PA was calculated by adding the MET-min/week of PAs with MET values <3. On the basis of overall MVPA, participants were grouped into six PA levels (ordinal variable), from inactive to very high. Those doing ≥600 MET-min/week of MVPA were considered as meeting the minimum recommended PA [17]. Adherence Adherence to omega-3 PUFA supplementation, placebo and multidomain sessions were assessed. For multidomain interventions, adherence was sub-divided into three different phases: adoption (first 2 months, corresponding to the intensive part of the intervention), transition (months 3–6) and maintenance (from month 7 onwards). People receiving ≥75% of the intervention prescribed were classified as adherent. Statistical analysis Descriptive statistics were presented as means (SD) or median (interquartile range—IQR) for continuous variables and absolute numbers and percentages for categorical variables. One-way ANOVA or the Kruskall–Wallis test and the chi-square test were used to examine differences across study groups at baseline, as appropriate. Mixed-effect linear regressions and mixed-effect ordered logistic regression (with a random effect at the participant’s level) were performed on the continuous PA variables (MVPA, LTPA, non-LTPA and light PA) and ordinal PA variable (PA levels), respectively. In all models, fixed effects were time (categorical variable), group and group-by-time interaction. Adjusted means for each group were obtained from the models and adjusted mean differences (against the placebo/usual care group) were calculated. Spearman rank correlations were used to examine the relationships of adherence to the multidomain intervention with score changes in MVPA and LTPA. Statistical significance was determined by a P < 0.05. Analyses followed the ITT principle and were performed with Stata (v.14.0, Texas, USA) statistical software. Exploratory analysis We performed several exploratory mixed-effect linear regressions on MVPA and LTPA. First, since executive function is associated to PA changes [8], we adjusted analyses for baseline executive function (as assessed by the Controlled Oral Word Association Test) [20]. Second, because the “induction phase” (i.e. 12 first sessions) was the heart of the MAPT multidomain intervention, a perprotocol population was defined for the present work as people who attended two or more sessions during this study phase. Analyses were ran to investigate the effects of the interventions in the whole perprotocol population, in adherents (≥75%) and non-adherents (<75%) to the 3-year period of the multidomain intervention, and according with participation in the two “boost sessions” (attendance to both sessions: yes or no) performed at 12- and 24-month follow-ups. Analyses stratified for the baseline values of the clinical dementia rating (CDR = 0 or CDR = 0.5) were also performed (both ITT and perprotocol populations). Results Table 1 shows the characteristics of the 1,679 participants. Groups did not differ at baseline. Around 70% of participants met the minimum recommended PA. Attendance to the multidomain intervention across the 3-year period was high (median 76.7%, IQR [41.9–88.4%]), but declined overtime from the adoption phase (first 2 months, 12 sessions: 91.7% [66.7–100%]), through the transition (months 3–6, once per month: 75% [50–100%]) and maintenance (months 7–36, once per month: 70.4% [18.5–85.2%]) phases; in the last year of the trial, more than 30% (n = 260) of participants had dropped out (adherence 66.6% [0–88.9%]). 429 (51.1%) people receiving the multidomain intervention adhered to ≥75% of the sessions and 732 (87.3%) attended to at least 2 sessions during the first 2 months of the trial (perprotocol population). Adherence to omega-3 and placebo during the trial were 81% (SD: 26.2%) and 82% (SD: 25.8%), respectively. Table 1. Baseline characteristics of the 1,679 study participants and differences among groupsa Variables  Multidomain + Omega-3 (n = 417)  Omega-3 (n = 422)  Multidomain (n = 420)  Placebo/usual care (n = 420)  Age, y  76 (4.4)  76.1 (4.7)  75.5 (4.2)  75.6 (4.4)  Women, n (%)  263 (63.1)  269 (63.7)  276 (65.7)  279 (66.4)  Education, n (%)   No diploma or primary school certificate  88 (21.3)  107 (26.6)  87 (21)  89 (21.6)   Secondary education  156 (37.7)  128 (31.8)  134 (32.3)  135 (32.8)   High-school diploma  56 (13.5)  51 (12.7)  64 (15.4)  71 (17.2)   University level  114 (27.5)  116 (28.9)  130 (31.3)  117 (28.4)  Mini mental state examination (0–30)  28.1 (1.6)  28.1 (1.6)  28 (1.6)  28.1 (1.5)  Clinical dementia rating, n (%) of 0.5  170 (40.8)  181 (43)  177 (42.1)  178 (42.4)  Geriatric depression scale (0–15)  3.2 (2.5)  3.3 (2.6)  3.3 (2.6)  3.3 (2.7)  Usual gait speed (m/s)  1.09 (0.3)  1.08 (0.2)  1.08 (0.3)  1.10 (0.3)  Short physical performance battery (0–12)  10.5 (1.8)  10.5 (1.5)  10.6 (1.7)  10.6 (1.6)  Body mass index (kg/m2)  26.2 (4.3)  26.3 (4.1)  26 (4)  26 (3.9)  MVPA (MET-min/week)b  1,017 (449–1,992)  1,113 (466–2,164)  1,146 (513–1,962)  1,131 (517–2,088)  LTPA (MET-min/week)b  681 (172–1,413)  774 (193–1,548)  774 (193–,523)  774 (258–1,659)  Housework + gardening PA (MET-min/week)b  157 (0–420)  105 (0–490)  137 (0–446)  105 (0–420)  Light PA (MET-min/week)b  0 (0–172)  0 (0–210)  0 (0–247)  0 (0–138)  PA levels, n (%)   Inactive  36 (8.6)  34 (8.1)  34 (8.1)  28 (6.7)   Very low active  42 (10.1)  44 (10.4)  41 (9.8)  40 (9.5)   Low active  58 (13.9)  41 (9.7)  42 (10)  54 (12.9)   Moderately active  47 (11.3)  51 (12.1)  48 (11.4)  54 (12.9)   High active  47 (11.3)  49 (11.6)  50 (11.9)  42 (10)   Very high active  187 (44.8)  203 (48.1)  205 (48.8)  202 (48.1)  Variables  Multidomain + Omega-3 (n = 417)  Omega-3 (n = 422)  Multidomain (n = 420)  Placebo/usual care (n = 420)  Age, y  76 (4.4)  76.1 (4.7)  75.5 (4.2)  75.6 (4.4)  Women, n (%)  263 (63.1)  269 (63.7)  276 (65.7)  279 (66.4)  Education, n (%)   No diploma or primary school certificate  88 (21.3)  107 (26.6)  87 (21)  89 (21.6)   Secondary education  156 (37.7)  128 (31.8)  134 (32.3)  135 (32.8)   High-school diploma  56 (13.5)  51 (12.7)  64 (15.4)  71 (17.2)   University level  114 (27.5)  116 (28.9)  130 (31.3)  117 (28.4)  Mini mental state examination (0–30)  28.1 (1.6)  28.1 (1.6)  28 (1.6)  28.1 (1.5)  Clinical dementia rating, n (%) of 0.5  170 (40.8)  181 (43)  177 (42.1)  178 (42.4)  Geriatric depression scale (0–15)  3.2 (2.5)  3.3 (2.6)  3.3 (2.6)  3.3 (2.7)  Usual gait speed (m/s)  1.09 (0.3)  1.08 (0.2)  1.08 (0.3)  1.10 (0.3)  Short physical performance battery (0–12)  10.5 (1.8)  10.5 (1.5)  10.6 (1.7)  10.6 (1.6)  Body mass index (kg/m2)  26.2 (4.3)  26.3 (4.1)  26 (4)  26 (3.9)  MVPA (MET-min/week)b  1,017 (449–1,992)  1,113 (466–2,164)  1,146 (513–1,962)  1,131 (517–2,088)  LTPA (MET-min/week)b  681 (172–1,413)  774 (193–1,548)  774 (193–,523)  774 (258–1,659)  Housework + gardening PA (MET-min/week)b  157 (0–420)  105 (0–490)  137 (0–446)  105 (0–420)  Light PA (MET-min/week)b  0 (0–172)  0 (0–210)  0 (0–247)  0 (0–138)  PA levels, n (%)   Inactive  36 (8.6)  34 (8.1)  34 (8.1)  28 (6.7)   Very low active  42 (10.1)  44 (10.4)  41 (9.8)  40 (9.5)   Low active  58 (13.9)  41 (9.7)  42 (10)  54 (12.9)   Moderately active  47 (11.3)  51 (12.1)  48 (11.4)  54 (12.9)   High active  47 (11.3)  49 (11.6)  50 (11.9)  42 (10)   Very high active  187 (44.8)  203 (48.1)  205 (48.8)  202 (48.1)  aValues are means (SD) for continuous and ordinal variables and absolute numbers (%) for categorical variables, unless otherwise stated. bValues are median (interquartile range). Table 2 shows the results of the mixed-effect linear regressions on PA continuous variables. The two multidomain groups increased their MVPA and LTPA at 6 months, followed by a decline until the end of the trial, getting back to their baseline PA values. The placebo/usual care and omega-3 alone groups declined from baseline to trial end, with within-group differences being significant at 2- (for LTPA) and 3-year (for MVPA and LTPA) follow-ups for both groups (see Figures S1 and S2 in the supplementary data available at Age and Ageing online). Compared to placebo/usual care, the multidomain plus omega-3 group had significantly higher MVPA at 6-month and higher LTPA at 6-month, 2- and 3-year follow-ups; whereas the multidomain alone had higher MVPA and LTPA at 6-month, 2- and 3-year follow-ups. Similar between-group differences were found regarding PA levels (Table S2 in the supplementary data available at Age and Ageing online). No differences were found for non-LTPA and light PA. Adherence to the multidomain intervention (Table S1 in the supplementary data available at Age and Ageing online) was not correlated with MVPA and LTPA change scores. Table 2. Effects of MAPT interventions on the different PA continuous outcomesa Outcomes  Multidomain + Omega-3  Multidomain  Omega-3  Placebo/usual care  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  MVPA   6 months  339 (107; 0.002)  449 (151; 0.003)  337 (106; 0.001)  447 (150; 0.003)  94 (107; 0.38)  203 (151; 0.18)  −110 (106; 0.30)     1 year  30 (109; 0.78)  61 (154; 0.69)  83 (109; 0.45)  113 (154; 0.46)  −18 (110; 0.87)  13 (155; 0.93)  −30 (109; 0.78)     2 years  60 (112; 0.59)  245 (158; 0.12)  168 (111; 0.13)  354 (157; 0.02)  −75 (112; 0.50)  110 (158; 0.48)  −185 (111; 0.09)     3 years  −33 (112; 0.77)  304 (159; 0.055)  90 (112; 0.42)  428 (158; 0.007)  −316 (112; 0.005)  21 (159; 0.89)  −337 (112; 0.003)    LTPA   6 months  300 (74; <0.001)  420 (104; <0.001)  326 (75; <0.001)  446 (103; <0.001)  48 (73; 0.51)  168 (104; 0.10)  −120 (73; 0.10)     1 year  74 (75; 0.33)  117 (106; 0.27)  62 (75; 0.40)  106 (106; 0.32)  −94 (75; 0.21)  −50 (106; 0.64)  −44 (75; 0.56)     2 years  83 (77; 0.28)  235 (108; 0.03)  95 (76; 0.21)  247 (108;0.02)  −171 (77; 0.03)  −19 (109; 0.86)  −152 (76; 0.047)     3 years  70 (77; 0.36)  316 (109; 0.004)  27 (77; 0.72)  273 (109; 0.01)  −241 (77; 0.002)  4 (109; 0.97)  −245 (77; 0.001)    Housework + gardening   6 months  41 (78; 0.60)  31 (110; 0.78)  16 (77; 0.83)  6 (109; 0.96)  49 (78; 0.53)  39 (110; 0.72)  10 (78; 0.89)     1 year  −38 (79; 0.63)  −27 (112; 0.81)  15 (79; 0.85)  26 (112; 0.81)  83 (80; 0.30)  94 (113; 0.40)  −11 (79; 0.89)     2 years  −21 (81; 0.79)  9 (115; 0.94)  68 (81; 0.40)  98 (114; 0.39)  91 (82; 0.26)  122 (115; 0.29)  −30 (81; 0.71)     3 years  −94 (82; 0.25)  −8 (115; 0.94)  68 (82; 0.41)  154 (115; 0.18)  −73 (82; 0.37)  14 (115; 0.90)  −87 (81; 0.29)    Light PA   6 months  129 (57; 0.02)  105 (80; 0.19)  21 (56; 0.71)  −4 (80; 0.96)  18 (57; 0.75)  −6 (80; 0.94)  25 (57; 0.66)     1 year  36 (58; 0.53)  97 (82; 0.24)  84 (58; 0.15)  114 (82; 0.08)  45 (58; 0.44)  106 (82; 0.20)  −60 (58; 0.29)     2 years  −7 (60; 0.90)  35 (84; 0.68)  −24 (59; 0.68)  18 (83; 0.83)  −4 (60; 0.95)  38 (84; 0.65)  −42 (59; 0.48)     3 years  −28 (60; 0.64)  44 (83; 0.60)  −104 (60; 0.08)  −32 (84; 0.70)  −49 (60; 0.41)  23 (84; 0.79)  −72 (59; 0.23)    Outcomes  Multidomain + Omega-3  Multidomain  Omega-3  Placebo/usual care  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  Within-group mean difference (SE; P-value)c  Between-group mean difference (SE; P-value)b  MVPA   6 months  339 (107; 0.002)  449 (151; 0.003)  337 (106; 0.001)  447 (150; 0.003)  94 (107; 0.38)  203 (151; 0.18)  −110 (106; 0.30)     1 year  30 (109; 0.78)  61 (154; 0.69)  83 (109; 0.45)  113 (154; 0.46)  −18 (110; 0.87)  13 (155; 0.93)  −30 (109; 0.78)     2 years  60 (112; 0.59)  245 (158; 0.12)  168 (111; 0.13)  354 (157; 0.02)  −75 (112; 0.50)  110 (158; 0.48)  −185 (111; 0.09)     3 years  −33 (112; 0.77)  304 (159; 0.055)  90 (112; 0.42)  428 (158; 0.007)  −316 (112; 0.005)  21 (159; 0.89)  −337 (112; 0.003)    LTPA   6 months  300 (74; <0.001)  420 (104; <0.001)  326 (75; <0.001)  446 (103; <0.001)  48 (73; 0.51)  168 (104; 0.10)  −120 (73; 0.10)     1 year  74 (75; 0.33)  117 (106; 0.27)  62 (75; 0.40)  106 (106; 0.32)  −94 (75; 0.21)  −50 (106; 0.64)  −44 (75; 0.56)     2 years  83 (77; 0.28)  235 (108; 0.03)  95 (76; 0.21)  247 (108;0.02)  −171 (77; 0.03)  −19 (109; 0.86)  −152 (76; 0.047)     3 years  70 (77; 0.36)  316 (109; 0.004)  27 (77; 0.72)  273 (109; 0.01)  −241 (77; 0.002)  4 (109; 0.97)  −245 (77; 0.001)    Housework + gardening   6 months  41 (78; 0.60)  31 (110; 0.78)  16 (77; 0.83)  6 (109; 0.96)  49 (78; 0.53)  39 (110; 0.72)  10 (78; 0.89)     1 year  −38 (79; 0.63)  −27 (112; 0.81)  15 (79; 0.85)  26 (112; 0.81)  83 (80; 0.30)  94 (113; 0.40)  −11 (79; 0.89)     2 years  −21 (81; 0.79)  9 (115; 0.94)  68 (81; 0.40)  98 (114; 0.39)  91 (82; 0.26)  122 (115; 0.29)  −30 (81; 0.71)     3 years  −94 (82; 0.25)  −8 (115; 0.94)  68 (82; 0.41)  154 (115; 0.18)  −73 (82; 0.37)  14 (115; 0.90)  −87 (81; 0.29)    Light PA   6 months  129 (57; 0.02)  105 (80; 0.19)  21 (56; 0.71)  −4 (80; 0.96)  18 (57; 0.75)  −6 (80; 0.94)  25 (57; 0.66)     1 year  36 (58; 0.53)  97 (82; 0.24)  84 (58; 0.15)  114 (82; 0.08)  45 (58; 0.44)  106 (82; 0.20)  −60 (58; 0.29)     2 years  −7 (60; 0.90)  35 (84; 0.68)  −24 (59; 0.68)  18 (83; 0.83)  −4 (60; 0.95)  38 (84; 0.65)  −42 (59; 0.48)     3 years  −28 (60; 0.64)  44 (83; 0.60)  −104 (60; 0.08)  −32 (84; 0.70)  −49 (60; 0.41)  23 (84; 0.79)  −72 (59; 0.23)    Note:SE, standard error. aAll PA outcomes are measured in MET-min/week. bComparisons are performed against the reference category group “Placebo/usual care”. Positive values indicates better PA in the intervention group compared to placebo/usual care, while negative values indicate better PA in the placebo/usual care group compared to intervention groups. cPositive values indicate increasing PA overtime. Exploratory analysis (see Tables S3–S5 in the supplementary data available at Age and Ageing online) adjusted for executive function provided similar results. Analysis using the perprotocol population gave unchanged findings. For non-adherent participants, although they have increased their LTPA at 6 months, they did not differ from placebo/usual care in the other time points. Results were similar for participants who attended and those who did not the two boost sessions. Similar results were also obtained regardless of participants’ cognitive status (CDR 0 and CDR 0.5) for both ITT and perprotocol populations, even though multidomain intervention’s positive effects have been slightly more pronounced among CDR 0.5. For all exploratory analyses, changes in MVPA and LTPA in the omega-3 PUFA alone group did not differ from those in the placebo/usual care. Discussion This work showed that a multidomain intervention focused on cognitive training, and nutritional and PA counselling increased the volumes (MVPA and LTPA) and levels of PA in the short-term (6-month follow-up) and limited their decline in the long-term (2- and 3-year follow-ups) among older adults with memory complaints, even among those with objective cognitive decline (CDR 0.5). Omega-3 PUFA supplementation had no effect on PA. In the only two RCTs employing multidomain interventions in an older population at-risk of cognitive decline, one study [9] used an intensive proof-of-concept intervention composed of several in-person sessions for the different components of the multidomain intervention, including supervised exercise training performed up to 5 times a week over 2 years; Ngandu and colleagues [9] found this intensive intervention increased the percentage of people doing PA at least twice a week. The other RCT [10] used individually tailored lifestyle advices (risk factors, including PA, were assessed at each visit) performed after each 4-month study visit over 6 years; this trial found the lifestyle intervention was ineffective to increase the number of participants meeting public health guidelines on PA [17]. Therefore, our findings add important information to this topic since this is the first study showing that a simple (not too much time-consuming), long-term multidomain intervention was able to improve PA behaviour among older adults with memory complaints, including those with objective cognitive decline. Moreover, our findings were independent of participants’ executive functioning, which was found to be an important predictor of PA in older adults [8, 21]. The multidomain intervention impacted only LTPA and MVPA, confirming our initial hypothesis. This is an important finding since MVPA and LTPA were found to be associated with good health outcomes [22–31]. The between-group differences for LTPA at the 6-month and 3-year follow-ups roughly corresponded to more than 100 min/week and 70 min/week, respectively, of brisk walking supplementary performed by the multidomain groups compared to placebo/usual care; these amounts of supplementary PA are clinically relevant outcomes. Indeed, data from six large longitudinal cohorts (n = 654,827) [22] have shown that doing less than 75 min/week of brisk walking was associated with a reduced risk of mortality by 19%. As a note of caution, MAPT population already had very high PA levels at baseline; the between-group differences found in this study might probably be less clinically relevant than if they had been found among sedentary individuals. As hypothesised, the effects of multidomain interventions were more pronounced in the first 6 months of the study probably because this corresponded to the most intensive period of the intervention. Although after the initial increase both multidomain groups have declined on PA, their PA values at 3 years were similar to their baseline values, whereas PA values in the non-multidomain groups declined consistently throughout the trial. Moreover, between-group differences remained significant at the study’s end, particularly among participants with attendance rates 75% or over, suggesting that high adherence played a role in the overtime sustainability of the multidomain intervention effects. This is a relevant information since we observed a decline in adherence rates for the multidomain intervention over the 3-year period, suggesting that finding out how to motivate people to participate even in simple, non-invasive and non-time-consuming interventions remains a major challenge in older populations. Regarding omega-3, previous trials, but not all [32], have found omega-3 PUFA supplementation increased muscle mass, function [11–13], and adaptive response to training (particularly among women) [33] in older adults. However, we failed to show an effect of omega-3 PUFA on PA, probably because PA is a multidimensional behaviour [34, 35]. Further research investigating the effects of omega-3 on both PA, physical capacity (e.g. maximal oxygen uptake (VO2max), which is less likely to be influenced by external factors than PA), and muscle function may provide complementary information to this field. The main strengths of this study are its RCT design, the large sample size, the long-term intervention period, good adherence rates, and the several time-point assessments that allowed us to obtain precise trajectories of PA overtime. However, limitations are worth mentioning: the study population was globally fit, with very high PA levels. Therefore, our findings may not apply to more vulnerable older adult populations; PA was assessed through a self-reported questionnaire, which may have reduced data accuracy. Future large-scale interventions should make efforts to include both subjective and objective PA measures; precise measures of muscle function and physical capacity were lacking; finally, it was impossible to disentangle the individual contribution of each component of the multidomain intervention. Although nutritional advice (particularly, through improved protein consumption) and cognitive stimulation may indirectly influence PA, we were unable to determine if such a multidomain approach leads to better results on PA than an intervention focusing solely on PA advices; this is particularly relevant under a cost-effectiveness perspective and should be addressed in future studies. In sum, we found that a multidomain intervention (cognitive training, and nutritional and PA advices) increased/maintained PA among older adults at-risk for cognitive decline over a 3-year period. Investigating if the effects of the intervention remain during the post-intervention period would inform on the long-term effectiveness of the approach. An observational longitudinal study examining the mediation role of changes in muscle function, physical capacity, and psychosocial variables (e.g. self-efficacy, social support) for improving PA levels in older populations would bring about valuable information to understand the mechanisms leading to sustained high PA in advanced ages. Key points Multidomain lifestyle intervention increased global and leisure-time moderate-to-vigorous PA in the short-term in people ≥70 years. The multidomain lifestyle intervention limited the decline of global and leisure-time PA in the long-term. Leisure-time PA increased to more than 100 min/week of brisk walking at 6 months and 70 min/week at 3 years. Supplementary data Supplementary data mentioned in the text are available to subscribers in Age and Ageing online. Authors’ contributions P.S.B. performed the statistical analysis, interpreted the data, drafted the article and approved the final version. Y.R. interpreted data, revised the article critically for important intellectual content and approved the final version. M.C. interpreted data, revised the article critically for important intellectual content and approved the final version. C.D. interpreted data, revised the article critically for important intellectual content and approved the final version. S.A. conceived the protocol and designed the whole MAPT trial, interpreted the data, revised the article critically for important intellectual content and approved the final version. B.V. conceived the protocol and designed the whole MAPT trial, interpreted the data, revised the article critically for important intellectual content and approved the final version. Conflict of interest None. Funding The MAPT study was supported by grants from the Gérontopôle of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the omega-3 supplement), Exhonit Therapeutics SA, Avid Radiopharmaceuticals Inc and in part by a grant from the French National Agency for Research called “Investissements d’Avenir” n°ANR-11-LABX-0018-01. The promotion of this study was supported by the University Hospital Center of Toulouse. The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d’Alzheimer (AMPA) and the UMR 1027 Unit INSERM-University of Toulouse III. The sponsor did not have a role in the study. References 1 GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. 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Predictors of physical activity change among adults using observational designs. Sports Med  2015; 45: 423– 41. Google Scholar CrossRef Search ADS PubMed  Author notes †Description of MAPT/DSA Groups can be found in the online supplementary data. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

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Age and AgeingOxford University Press

Published: Mar 1, 2018

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