JAMDA 16 (2015) 998e1001
JAMDA journal homepage: www.jamda.com
Letters to the Editor
Potential for a “Memory Gym” Intervention to Delay Conversion of Mild Cognitive Impairment to Dementia To the Editor: We read with interest the results of the Study of Mental and Resistance Training (SMART)1 comparing 2 interventions: progressive resistance training (PRT) and cognitive training (CT), either in isolation or combination, in patients with mild cognitive impairment (MCI). SMART investigates the effects of combining these 2 distinct training paradigms2 using a randomized, doubleblind, double-sham controlled method [randomized controlled trial (RCT)]. As cognitive enhancers are ineffective and potentially harmful in MCI,3 nonpharmaceutical approaches are increasingly being considered as a therapeutic option. Although combining treatment modalities is not new, multimodal approaches are now increasingly being trialed in MCI and dementia. Tailored intervention strategies incorporating combinations of diet, exercise, stress reduction, and cognitive stimulation have shown potential in patients with amnestic MCI,4 but the evidence for the efficacy of single or combined interventions remains limited. This study, the first RCT investigating combined strategies, concludes that PRT alone improved global cognitive function. Contrary to other studies, CT did not improve global cognitive and functional outcomes. It did, however, transiently attenuate decline in memory at 6 months. To date, no study has investigated the effects of a more extensive suite of lifestyle strategies, incorporating PRT, CT, and other interventions, on conversion of MCI to dementia. We recently conducted a case-control trial comparing a 6-week “memory-gym” group-therapy program, with one 3-month booster session, to usual care, among consecutive patients recently diagnosed with MCI, according to Petersens’ criteria,5 attending a university hospital memory clinic. The “memory-gym” suite of strategies included weekly CT (using 3 commercially available apps, on tablet computers, according to an established protocol6), for
1 hour per week with an additional hour of compensatory techniques, dietary advice, exercise instructions, stress management, mindfulness techniques, or art therapy. Patients were included if baseline and end-point (standardized at 6 months apart) standardized Mini-Mental State Examination (SMMSE), Quick Mild Cognitive Impairment (Qmci) screen,7,8 and Caregiver Burden (modified Zarit) scores were available. In all, 13 participants completed the intervention in 2 groups, median age 72 years (interquartile 6) compared with 76 (11) for controls (n ¼ 17). The median follow-up was 18 months vs 18.5 months, respectively (P ¼ .72). No significant differences in baseline age, gender, education, SMMSE, Qmci, or caregiver scores were found (Table 1). There was a significant difference in median 6-month rate of change in Qmci scores for those with MCI, þ0.4/100 points vs e3.5/ 100 points (P ¼ .024). No significant differences in SMMSE (e0.66/ 30 vs e0.39/30, P ¼ .58), or Caregiver Burden (0 vs 0, P ¼ .55) scores were shown (Figure 1). Only 15% (2/13) of participants with MCI converted to dementia compared with 47% (8/17) of controls (P ¼ .12). These results suggest that a multimodality intervention using educational strategies, delivered in the form of a “memory-gym,” by trained therapists aligned to a memory clinic, may slow progression in MCI. It supports the results of the SMART and a similar study in a nursing home utilizing combined cognitive stimulation therapy and exercise.9 Although changes associated with the “memory-gym” were small and of uncertain clinical significance, if sustained over years, the compounding effects may have significant clinical benefits. Limitations include the short training duration, lack of randomization or blinding, and the inability to isolate individual components of the “gym.” Furthermore, no recognized global assessment such as the Alzheimer Disease Assessment Scale- Cognitive Subscale test (ADAS-cog) was used. However, the Qmci is an accurate instrument for measuring MCI,6 correlating with the Alzheimer Disease Assessment Scale-Cognitive Subscale, Clinical Dementia Rating scale, and the Lawton-Brody Activities of Daily Living scale in clinical trials.10 While agreeing with
Table 1 Baseline Characteristics, Median, and IQR, of Participants (Cases) and Nonparticipants (Controls) Including Median 6-Month Rates of Decline in SMMSE and Qmci Scores Group
Participants Nonparticipants P ¼ x (Cases) (Controls)
Number 13 Follow-up in months (median and IQR) 18 (5) Age (median and IQR) 72 (6) Gender (% female) 71% Education in years (median and IQR) 14 (3) SMMSE (median and IQR) 29 (4) Qmci (median and IQR) 59.5 (15) Caregiver scores (median and IQR) 2 (5) IQR, interquartile range.
17 18.5 (7.75) 76 (11) 70% 12 (6) 28.5 (3) 56 (11) 6 (11)
e .72 .26 1.0 .71 .51 .98 .41
Fig. 1. Comparison of median 6-month rates of decline in SMMSE and Qmci scores in those with mild cognitive impairment, between participants (cases) and nonparticipants (controls).
Letters to the Editor / JAMDA 16 (2015) 998e1001
Fiatarone Singh et al1 on the need for large-scale trials to “explore the mechanism of cognitive/neural adaptations to PRT,” and “demonstrate that PRT can reduce incident dementia,” we suggest that it is also important to clarify if the effects are cumulative with other therapies, including drugs, if they differ according to MCI subtype, if differing factors such as home environments and personality types may create bias, and the extent to which maintenance therapy is required. RCTs are now required to clarify if and how tailored interventions should be used in the management of MCI.
999
St Finbarr’s Hospital Cork City, Ireland http://dx.doi.org/10.1016/j.jamda.2015.01.081
Reply to the Letter to the Editor by O’Caoimh et al
References 1. Fiatarone Singh MA, Gates N, Saigal N, et al. The Study of Mental and Resistance Training (SMART) StudydResistance training and/or cognitive training in mild cognitive impairment: A randomized, double-blind, double-sham controlled trial. J Am Med Dir Assoc 2014;15:873e880. 2. Gates NJ, Sachdev PS, Fiatarone Singh MA, Valenzuela M. Cognitive and memory training in adults at risk of dementia: a systematic review. BMC Geriatr 2011;11:55. 3. Tricco AC, Soobiah C, Berliner S, et al. Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: A systematic review and metaanalysis. CMAJ 2013;185:1393e1401. 4. Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging 2014;6:707e717. 5. Petersen RC, Smith GM, Ivnik RJ, et al. Mild cognitive impairment: Clinical characterisation and outcome. Arch Neurol 1999;56:303e308. 6. Scanlon L, O’Shea E, O’Caoimh R, Timmons S. Assessment of Cognition using Cognitive Training Applications. Age Ageing 2014;43:ii24. 7. O’Caoimh R, Gao Y, McGlade C, et al. Comparison of the Quick Mild Cognitive Impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment. Age Ageing 2012;41:624e629. 8. O’Caoimh R, Gao Y, Gallagher P, et al. Which part of the Quick Mild Cognitive Impairment Screen (Qmci) discriminates between normal cognition, mild cognitive impairment and dementia? Age Ageing 2013;42:324e330. 9. Loraine J, Taylor S, McAllister M. Cognitive and physical stimulation therapy. J Am Med Dir Assoc 2014;15:140e141. 10. O’Caoimh R, Svendrovski A, Johnston B, et al. The Quick Mild Cognitive Impairment screen correlated with the Standardized Alzheimer’s Disease Assessment Scale-cognitive section in clinical trials. J Clin Epidemiol 2014;67: 87e92.
Rónán O’Caoimh, MD Center for Gerontology and Rehabilitation University College Cork St Finbarrs’ Hospital Cork City, Ireland Stephen Sato, OTRP Department of Occupational Therapy St Finbarrs’ Hospital Cork City, Ireland Judy Wall, PhD Department of Clinical Psychology Le Chéile, St Finbarrs’ Hospital Cork City, Ireland Estera Igras, MD Center for Gerontology and Rehabilitation University College Cork St Finbarrs’ Hospital Cork City, Ireland Mary J. Foley, ANP Assessment and Treatment Center St Finbarrs’ Hospital Cork City, Ireland Suzanne Timmons, MB, MSc, MD, William Molloy, MB Center for Gerontology and Rehabilitation University College Cork
To the Editor: We have read with interest the letter of O’Caoimh et al entitled, “Potential for a ‘Memory Gym’ intervention to delay conversion of mild cognitive impairment to dementia,” which was submitted as correspondence to the publication of our Study of Mental and Resistance Training (SMART) trial.1 This letter describes the results of their Memory Gym study. The idea that combinations of interventions in different domains might be optimal for preservation of brain function is supported by a wealth of animal and human literature on enriched environments.2 Epidemiologic studies in human cohorts suggest that a wide variety of physical, psychological, social, educational, cognitive, occupational, nutritional, and spiritual factors may impact rates of cognitive decline, superimposed on genetic, age-related, and pathophysiological profiles. However, the exact combination of strategies that would be most effective clinically, or even whether single interventions are more or less potent than multimodal interventions for either prevention or treatment of cognitive impairment is not at all clear from existing published literature, and further robust, empirical investigation is needed. O’Caoimh et al describe the results of a nonrandomized controlled trial of one such multimodal intervention comprised of computerized cognitive training (CT) plus dietary or exercise advice, stress management, mindfulness, or art therapy delivered over 6 weeks (2 hours/week) to older adults with newly diagnosed mild cognitive impairment (MCI). It is not clear if controls were concurrent or historic. Exactly what was prescribed or how it was determined what to offer, and the adoption and adherence to any of the program elements is not presented. They report a significant stabilization of Quick Mild Cognitive Impairment scores compared to declines in controls, but no difference in Mini-mental State Examination or Caregiver Burden scores, as well as a tendency for less Memory Gym participants to convert to dementia. It is not clear how dementia was diagnosed or whether it was blindly assessed, and whether it was assessed after 6 weeks, 6 months, or 18 months. Participant characteristics in Table 1 reveal that the nonrandomized allocation resulted in controls who were 4 years older, had 2 years less education, and higher Caregiver Burden scores at baseline. Although these differences were not significant in this small sample size (n ¼ 30), they are potentially clinically relevant in magnitude, and evaluation of outcomes should have been adjusted for these confounders. The age difference alone might be enough to explain the differential rate of progression to dementia. No statistical methods are presented to determine if this was done. No standard deviations are presented in Figure 1, so it is not possible to calculate the effect size of the Quick Mild Cognitive Impairment results reported to compare with other literature. Given that there was no change in Caregiver Burden at 18 months, it is surprising that nearly one-half of the controls are reported to have progressed to dementia. Finally, it is stated that 13 people completed the intervention, but it is not known how
JAMDA journal homepage: www.jamda.com
Letters to the Editor
Potential for a “Memory Gym” Intervention to Delay Conversion of Mild Cognitive Impairment to Dementia To the Editor: We read with interest the results of the Study of Mental and Resistance Training (SMART)1 comparing 2 interventions: progressive resistance training (PRT) and cognitive training (CT), either in isolation or combination, in patients with mild cognitive impairment (MCI). SMART investigates the effects of combining these 2 distinct training paradigms2 using a randomized, doubleblind, double-sham controlled method [randomized controlled trial (RCT)]. As cognitive enhancers are ineffective and potentially harmful in MCI,3 nonpharmaceutical approaches are increasingly being considered as a therapeutic option. Although combining treatment modalities is not new, multimodal approaches are now increasingly being trialed in MCI and dementia. Tailored intervention strategies incorporating combinations of diet, exercise, stress reduction, and cognitive stimulation have shown potential in patients with amnestic MCI,4 but the evidence for the efficacy of single or combined interventions remains limited. This study, the first RCT investigating combined strategies, concludes that PRT alone improved global cognitive function. Contrary to other studies, CT did not improve global cognitive and functional outcomes. It did, however, transiently attenuate decline in memory at 6 months. To date, no study has investigated the effects of a more extensive suite of lifestyle strategies, incorporating PRT, CT, and other interventions, on conversion of MCI to dementia. We recently conducted a case-control trial comparing a 6-week “memory-gym” group-therapy program, with one 3-month booster session, to usual care, among consecutive patients recently diagnosed with MCI, according to Petersens’ criteria,5 attending a university hospital memory clinic. The “memory-gym” suite of strategies included weekly CT (using 3 commercially available apps, on tablet computers, according to an established protocol6), for
1 hour per week with an additional hour of compensatory techniques, dietary advice, exercise instructions, stress management, mindfulness techniques, or art therapy. Patients were included if baseline and end-point (standardized at 6 months apart) standardized Mini-Mental State Examination (SMMSE), Quick Mild Cognitive Impairment (Qmci) screen,7,8 and Caregiver Burden (modified Zarit) scores were available. In all, 13 participants completed the intervention in 2 groups, median age 72 years (interquartile 6) compared with 76 (11) for controls (n ¼ 17). The median follow-up was 18 months vs 18.5 months, respectively (P ¼ .72). No significant differences in baseline age, gender, education, SMMSE, Qmci, or caregiver scores were found (Table 1). There was a significant difference in median 6-month rate of change in Qmci scores for those with MCI, þ0.4/100 points vs e3.5/ 100 points (P ¼ .024). No significant differences in SMMSE (e0.66/ 30 vs e0.39/30, P ¼ .58), or Caregiver Burden (0 vs 0, P ¼ .55) scores were shown (Figure 1). Only 15% (2/13) of participants with MCI converted to dementia compared with 47% (8/17) of controls (P ¼ .12). These results suggest that a multimodality intervention using educational strategies, delivered in the form of a “memory-gym,” by trained therapists aligned to a memory clinic, may slow progression in MCI. It supports the results of the SMART and a similar study in a nursing home utilizing combined cognitive stimulation therapy and exercise.9 Although changes associated with the “memory-gym” were small and of uncertain clinical significance, if sustained over years, the compounding effects may have significant clinical benefits. Limitations include the short training duration, lack of randomization or blinding, and the inability to isolate individual components of the “gym.” Furthermore, no recognized global assessment such as the Alzheimer Disease Assessment Scale- Cognitive Subscale test (ADAS-cog) was used. However, the Qmci is an accurate instrument for measuring MCI,6 correlating with the Alzheimer Disease Assessment Scale-Cognitive Subscale, Clinical Dementia Rating scale, and the Lawton-Brody Activities of Daily Living scale in clinical trials.10 While agreeing with
Table 1 Baseline Characteristics, Median, and IQR, of Participants (Cases) and Nonparticipants (Controls) Including Median 6-Month Rates of Decline in SMMSE and Qmci Scores Group
Participants Nonparticipants P ¼ x (Cases) (Controls)
Number 13 Follow-up in months (median and IQR) 18 (5) Age (median and IQR) 72 (6) Gender (% female) 71% Education in years (median and IQR) 14 (3) SMMSE (median and IQR) 29 (4) Qmci (median and IQR) 59.5 (15) Caregiver scores (median and IQR) 2 (5) IQR, interquartile range.
17 18.5 (7.75) 76 (11) 70% 12 (6) 28.5 (3) 56 (11) 6 (11)
e .72 .26 1.0 .71 .51 .98 .41
Fig. 1. Comparison of median 6-month rates of decline in SMMSE and Qmci scores in those with mild cognitive impairment, between participants (cases) and nonparticipants (controls).
Letters to the Editor / JAMDA 16 (2015) 998e1001
Fiatarone Singh et al1 on the need for large-scale trials to “explore the mechanism of cognitive/neural adaptations to PRT,” and “demonstrate that PRT can reduce incident dementia,” we suggest that it is also important to clarify if the effects are cumulative with other therapies, including drugs, if they differ according to MCI subtype, if differing factors such as home environments and personality types may create bias, and the extent to which maintenance therapy is required. RCTs are now required to clarify if and how tailored interventions should be used in the management of MCI.
999
St Finbarr’s Hospital Cork City, Ireland http://dx.doi.org/10.1016/j.jamda.2015.01.081
Reply to the Letter to the Editor by O’Caoimh et al
References 1. Fiatarone Singh MA, Gates N, Saigal N, et al. The Study of Mental and Resistance Training (SMART) StudydResistance training and/or cognitive training in mild cognitive impairment: A randomized, double-blind, double-sham controlled trial. J Am Med Dir Assoc 2014;15:873e880. 2. Gates NJ, Sachdev PS, Fiatarone Singh MA, Valenzuela M. Cognitive and memory training in adults at risk of dementia: a systematic review. BMC Geriatr 2011;11:55. 3. Tricco AC, Soobiah C, Berliner S, et al. Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: A systematic review and metaanalysis. CMAJ 2013;185:1393e1401. 4. Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging 2014;6:707e717. 5. Petersen RC, Smith GM, Ivnik RJ, et al. Mild cognitive impairment: Clinical characterisation and outcome. Arch Neurol 1999;56:303e308. 6. Scanlon L, O’Shea E, O’Caoimh R, Timmons S. Assessment of Cognition using Cognitive Training Applications. Age Ageing 2014;43:ii24. 7. O’Caoimh R, Gao Y, McGlade C, et al. Comparison of the Quick Mild Cognitive Impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment. Age Ageing 2012;41:624e629. 8. O’Caoimh R, Gao Y, Gallagher P, et al. Which part of the Quick Mild Cognitive Impairment Screen (Qmci) discriminates between normal cognition, mild cognitive impairment and dementia? Age Ageing 2013;42:324e330. 9. Loraine J, Taylor S, McAllister M. Cognitive and physical stimulation therapy. J Am Med Dir Assoc 2014;15:140e141. 10. O’Caoimh R, Svendrovski A, Johnston B, et al. The Quick Mild Cognitive Impairment screen correlated with the Standardized Alzheimer’s Disease Assessment Scale-cognitive section in clinical trials. J Clin Epidemiol 2014;67: 87e92.
Rónán O’Caoimh, MD Center for Gerontology and Rehabilitation University College Cork St Finbarrs’ Hospital Cork City, Ireland Stephen Sato, OTRP Department of Occupational Therapy St Finbarrs’ Hospital Cork City, Ireland Judy Wall, PhD Department of Clinical Psychology Le Chéile, St Finbarrs’ Hospital Cork City, Ireland Estera Igras, MD Center for Gerontology and Rehabilitation University College Cork St Finbarrs’ Hospital Cork City, Ireland Mary J. Foley, ANP Assessment and Treatment Center St Finbarrs’ Hospital Cork City, Ireland Suzanne Timmons, MB, MSc, MD, William Molloy, MB Center for Gerontology and Rehabilitation University College Cork
To the Editor: We have read with interest the letter of O’Caoimh et al entitled, “Potential for a ‘Memory Gym’ intervention to delay conversion of mild cognitive impairment to dementia,” which was submitted as correspondence to the publication of our Study of Mental and Resistance Training (SMART) trial.1 This letter describes the results of their Memory Gym study. The idea that combinations of interventions in different domains might be optimal for preservation of brain function is supported by a wealth of animal and human literature on enriched environments.2 Epidemiologic studies in human cohorts suggest that a wide variety of physical, psychological, social, educational, cognitive, occupational, nutritional, and spiritual factors may impact rates of cognitive decline, superimposed on genetic, age-related, and pathophysiological profiles. However, the exact combination of strategies that would be most effective clinically, or even whether single interventions are more or less potent than multimodal interventions for either prevention or treatment of cognitive impairment is not at all clear from existing published literature, and further robust, empirical investigation is needed. O’Caoimh et al describe the results of a nonrandomized controlled trial of one such multimodal intervention comprised of computerized cognitive training (CT) plus dietary or exercise advice, stress management, mindfulness, or art therapy delivered over 6 weeks (2 hours/week) to older adults with newly diagnosed mild cognitive impairment (MCI). It is not clear if controls were concurrent or historic. Exactly what was prescribed or how it was determined what to offer, and the adoption and adherence to any of the program elements is not presented. They report a significant stabilization of Quick Mild Cognitive Impairment scores compared to declines in controls, but no difference in Mini-mental State Examination or Caregiver Burden scores, as well as a tendency for less Memory Gym participants to convert to dementia. It is not clear how dementia was diagnosed or whether it was blindly assessed, and whether it was assessed after 6 weeks, 6 months, or 18 months. Participant characteristics in Table 1 reveal that the nonrandomized allocation resulted in controls who were 4 years older, had 2 years less education, and higher Caregiver Burden scores at baseline. Although these differences were not significant in this small sample size (n ¼ 30), they are potentially clinically relevant in magnitude, and evaluation of outcomes should have been adjusted for these confounders. The age difference alone might be enough to explain the differential rate of progression to dementia. No statistical methods are presented to determine if this was done. No standard deviations are presented in Figure 1, so it is not possible to calculate the effect size of the Quick Mild Cognitive Impairment results reported to compare with other literature. Given that there was no change in Caregiver Burden at 18 months, it is surprising that nearly one-half of the controls are reported to have progressed to dementia. Finally, it is stated that 13 people completed the intervention, but it is not known how
