The PACE Study: A Randomized Clinical Trial of Cognitive Activity Strategy Training for Older People with Mild Cognitive Impairment Mandy R. Vidovich, B.Sc., M.Clin. Neuro, Nicola T. Lautenschlager, M.D., F.R.A.N.Z.C.P., Leon Flicker, M.B.B.S., Ph.D., F.R.A.C.P., Linda Clare, B.A., M.Sc., Ph.D., F.R.Ps.S., Kieran McCaul, B.Sc., Ph.D., Osvaldo P. Almeida, M.D., Ph.D., F.R.A.N.Z.C.P.
Objectives: The role of cognition-focused interventions in reducing cognitive decline in older people remains uncertain. This study aimed to clarify whether a group cognitive activity (CA) strategy-training program would decrease the 2-year rate of cognitive decline of people with mild cognitive impairment (MCI). Design: Randomized controlled trial. Setting: One study site. Participants: 160 older adults with MCI 65 years of age (mean: 75, SD: 5.8). Intervention: Five-week CA strategy training or a control nonspecific educational program. The primary outcome measure was change from baseline in the total score on the Cambridge Cognitive Examination-Revised (CAMCOG-R). Secondary outcomes of interest included changes in memory, attention, executive functions, mood, and quality of life. Endpoints were collected 10, 52, and 104 weeks post baseline. Results: Intention to treat analysis identified no significant difference in CAMCOG-R scores over time between the two groups (mean difference: 0.36, 95% CI: 1.02,0.29) or across secondary outcome measures. The exceptions were better performance of the CA group on immediate attention (Digit Span Forwards, adjusted mean difference: 0.15, 95% CI: 0.01,0.30) and better quality of life (adjusted mean difference: 0.57, 95% CI: 0.10,1.04) compared with controls. Conclusions: The devised program of CA did not improve general cognitive performance of older adults with MCI over a period of 2 years. Although favorable, the beneficial effects of the intervention on attention and quality of life were small, and of uncertain significance. (Am J Geriatr Psychiatry 2014; -:-e-) Key Words: Neuropsychology, cognition, dementia, prevention, intervention
Received October 24, 2013; revised April 1, 2014; accepted April 2, 2014. From the Western Australia Centre for Health and Ageing (MRV, NTL, LF, KM, OPA), School of Psychiatry and Clinical Neurosciences & Centre for Medical Research, University of Western Australia and Royal Perth Hospital, Australia; Academic Unit for Psychiatry of Old Age (NTL), St Vincent’s Health, Department of Psychiatry, University of Melbourne, Australia; and Research in Ageing and Cognitive Health (LC), School of Psychology, Bangor University, Wales, United Kingdom. Send correspondence and reprint requests to Mandy R. Vidovich, B.Sc., M.Clin. Neuro, WACHA (M577), The University of Western Australia, 35 Stirling Highway, Crawley Western Australia 6009. e-mail: [email protected] Ó 2014 American Association for Geriatric Psychiatry http://dx.doi.org/10.1016/j.jagp.2014.04.002
Am J Geriatr Psychiatry
-:-, -
2014
1
The PACE Study for MCI
W
ith the aging of the world’s population, dementia is becoming an increasingly important public health issue.1 Available treatments for Alzheimer disease do not alter disease progression and, therefore, focus has been shifting towards prevention. Identifying modifiable risk factors for dementia is a burgeoning area of interest, with significant attention being given to the benefits derived from participation in mentally stimulating activities. Observational studies have shown that people involved in such activities (e.g., reading, playing Mahjong) have better cognitive function and a reduced risk of dementia over time.2e4 Similarly, cognition-focused interventions (CFIs) utilizing relatively preserved cognitive functions aim to maintain or delay further decline.5 Improvements on subjective measures of mood and quality of life have also been reported,6 although the clinical impact of CFIs remains to be established. There are, however, few randomized controlled trials (RCTs) of CFIs with older adults (healthy or otherwise) and, because of methodological shortcomings, their results have been difficult to generalize.5,7e11 These issues were highlighted in a recent publication reviewing the varied therapeutic approaches targeting individuals with cognitive compromise and the lack of theoretically driven models for evaluating efficacy.12 Importantly, it remains to be established if participation in this type of intervention can prevent dementia. This is particularly pertinent for people with mild cognitive impairment (MCI), who are at increased risk of conversion to dementia.13 In light of the many varied factors that seem to influence cognitive functioning, individuals with MCI are viewed as an appropriate target group for dementia prevention strategies. Identifying the role that CFIs can play in stabilizing or reversing decline in this group of patients would have significant public health implications. The primary objective of the Promoting Healthy Ageing with Cognitive Exercise (PACE) RCT was to determine whether a cognitive activity training strategy (CATS) program could decrease the rate of decline among older people with MCI over a follow-up period of two years. To this end, participants were provided strategies and coaching during group sessions to enhance cognitive functioning. A nonspecific educational “control” group was offered a 5-week program of more generalized presentations on healthy aging and retirement. We hypothesized that participants randomized to the CATS group would experience less
2
cognitive decline than older adults allocated to the educational group.
METHODS Participants and Design This single-blind RCT was registered with the Australian Clinical Trials Registry (ACTRN12608000 556347). Detailed information about the participants, training program, experimental design and outcome measures has been provided elsewhere.14 Briefly, 324 community volunteers were screened for the presence of MCI according to published criteria.15 Clinical evaluation of MCI was established by identifying performances 1.5 standard deviations below age and sex norms on any Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) cognitive task.16 Additionally, participants had to be aged 65 years or over, proficient in spoken and written English, and able to travel to the research center. Individuals with an established diagnosis of dementia according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, criteria for research17 or who showed signs of cognitive impairment (as evidenced by a Mini Mental State Examination MMSE;18 score of 23 or less) were excluded. Additional exclusion criteria included current psychiatric disorder, current hazardous or harmful alcohol consumption,19 or a medical condition that could compromise participation in the study tasks (such as sensory impairment) or reduce medium-term survival (e.g., advanced cancer). Individuals who reported a clinical history of stroke associated with permanent disability were also excluded. One hundred sixty adults met criteria and attended a baseline assessment prior to being randomized into either the CATS or the control Education group. The human research ethics committees of the University of Western Australia and of the Royal Perth Hospital approved this study and all participants provided written informed consent. Procedures of this study followed the principles of the Declaration of Helsinki for Human Rights. Outcome Measures and Timeline of the Study Further assessments post baseline occurred at 10 weeks, 52 weeks, and 104 weeks. The primary outcome measure was the Cambridge Cognitive Examination
Am J Geriatr Psychiatry
-:-, -
2014
Vidovich et al.
TABLE 1. Outline of the Assessments and Timelines of the PACE Trial Clinical Screen
Baseline
10 weeks
52 weeks
104 weeks
Outcome Measure
PHQ-9 (36)
X
X
X
X
X
Mood
CERAD (16)
X
X
X
Global Cognition
MMSE (18)
X
X
X
Global Cognition
AUDIT (19)
X
X
X
Alcohol Use
SAILS (37)
X
X
X
Functional Ability
MHQ CAMCOG-R (20)
X
Assessment Tool
X
X
X X
X X
Health Issues Global Cognition
CVLT-II (21)
X
X
X
X
Memory
Digit Span (22)
X
X
X
X
Attention
Symbol Search (22)
X
X
X
X
Processing Speed
TMTA (23)
X
X
X
X
Attention/Proc. Speed
TMTB (23)
X
X
X
X
Executive Functions
COWAT (23)
X
X
X
X
Executive Functions
LAQ (2) PAQ (38) SNSQ (39)
X X X
X X X
X X X
X X X
Leisure Activity Physical Activity Social Activity
MFQ (40)
X
X
X
X
Perception of Memory
QOL-AD (41)
X
X
X
X
Quality of Life
Measure/Comment Total Score (0e27) Y Scores ¼ [ Mood Individual Subtest Scores [ Scores ¼ [ Performance Total Score (0e30) [ Scores ¼ [ Performance Total Score (0e40) Y Scores ¼ Y Consumption Total Score (0e150) [ Scores ¼ [ Performance Yes or No Total Score (0e105) [ Scores ¼ [ Performance Recall Scores [ Scores ¼ [ Performance Total Scores [ Scores ¼ [ Performance Total Score (0e60) [ Scores ¼ [ Performance Total Time (seconds) Y Scores ¼ [ Performance Total Time (seconds) Y Scores ¼ [ Performance Total Score [ Scores ¼ [ Performance Rarely or Frequently Active (2.5 hrs) or Inactive (
Objectives: The role of cognition-focused interventions in reducing cognitive decline in older people remains uncertain. This study aimed to clarify whether a group cognitive activity (CA) strategy-training program would decrease the 2-year rate of cognitive decline of people with mild cognitive impairment (MCI). Design: Randomized controlled trial. Setting: One study site. Participants: 160 older adults with MCI 65 years of age (mean: 75, SD: 5.8). Intervention: Five-week CA strategy training or a control nonspecific educational program. The primary outcome measure was change from baseline in the total score on the Cambridge Cognitive Examination-Revised (CAMCOG-R). Secondary outcomes of interest included changes in memory, attention, executive functions, mood, and quality of life. Endpoints were collected 10, 52, and 104 weeks post baseline. Results: Intention to treat analysis identified no significant difference in CAMCOG-R scores over time between the two groups (mean difference: 0.36, 95% CI: 1.02,0.29) or across secondary outcome measures. The exceptions were better performance of the CA group on immediate attention (Digit Span Forwards, adjusted mean difference: 0.15, 95% CI: 0.01,0.30) and better quality of life (adjusted mean difference: 0.57, 95% CI: 0.10,1.04) compared with controls. Conclusions: The devised program of CA did not improve general cognitive performance of older adults with MCI over a period of 2 years. Although favorable, the beneficial effects of the intervention on attention and quality of life were small, and of uncertain significance. (Am J Geriatr Psychiatry 2014; -:-e-) Key Words: Neuropsychology, cognition, dementia, prevention, intervention
Received October 24, 2013; revised April 1, 2014; accepted April 2, 2014. From the Western Australia Centre for Health and Ageing (MRV, NTL, LF, KM, OPA), School of Psychiatry and Clinical Neurosciences & Centre for Medical Research, University of Western Australia and Royal Perth Hospital, Australia; Academic Unit for Psychiatry of Old Age (NTL), St Vincent’s Health, Department of Psychiatry, University of Melbourne, Australia; and Research in Ageing and Cognitive Health (LC), School of Psychology, Bangor University, Wales, United Kingdom. Send correspondence and reprint requests to Mandy R. Vidovich, B.Sc., M.Clin. Neuro, WACHA (M577), The University of Western Australia, 35 Stirling Highway, Crawley Western Australia 6009. e-mail: [email protected] Ó 2014 American Association for Geriatric Psychiatry http://dx.doi.org/10.1016/j.jagp.2014.04.002
Am J Geriatr Psychiatry
-:-, -
2014
1
The PACE Study for MCI
W
ith the aging of the world’s population, dementia is becoming an increasingly important public health issue.1 Available treatments for Alzheimer disease do not alter disease progression and, therefore, focus has been shifting towards prevention. Identifying modifiable risk factors for dementia is a burgeoning area of interest, with significant attention being given to the benefits derived from participation in mentally stimulating activities. Observational studies have shown that people involved in such activities (e.g., reading, playing Mahjong) have better cognitive function and a reduced risk of dementia over time.2e4 Similarly, cognition-focused interventions (CFIs) utilizing relatively preserved cognitive functions aim to maintain or delay further decline.5 Improvements on subjective measures of mood and quality of life have also been reported,6 although the clinical impact of CFIs remains to be established. There are, however, few randomized controlled trials (RCTs) of CFIs with older adults (healthy or otherwise) and, because of methodological shortcomings, their results have been difficult to generalize.5,7e11 These issues were highlighted in a recent publication reviewing the varied therapeutic approaches targeting individuals with cognitive compromise and the lack of theoretically driven models for evaluating efficacy.12 Importantly, it remains to be established if participation in this type of intervention can prevent dementia. This is particularly pertinent for people with mild cognitive impairment (MCI), who are at increased risk of conversion to dementia.13 In light of the many varied factors that seem to influence cognitive functioning, individuals with MCI are viewed as an appropriate target group for dementia prevention strategies. Identifying the role that CFIs can play in stabilizing or reversing decline in this group of patients would have significant public health implications. The primary objective of the Promoting Healthy Ageing with Cognitive Exercise (PACE) RCT was to determine whether a cognitive activity training strategy (CATS) program could decrease the rate of decline among older people with MCI over a follow-up period of two years. To this end, participants were provided strategies and coaching during group sessions to enhance cognitive functioning. A nonspecific educational “control” group was offered a 5-week program of more generalized presentations on healthy aging and retirement. We hypothesized that participants randomized to the CATS group would experience less
2
cognitive decline than older adults allocated to the educational group.
METHODS Participants and Design This single-blind RCT was registered with the Australian Clinical Trials Registry (ACTRN12608000 556347). Detailed information about the participants, training program, experimental design and outcome measures has been provided elsewhere.14 Briefly, 324 community volunteers were screened for the presence of MCI according to published criteria.15 Clinical evaluation of MCI was established by identifying performances 1.5 standard deviations below age and sex norms on any Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) cognitive task.16 Additionally, participants had to be aged 65 years or over, proficient in spoken and written English, and able to travel to the research center. Individuals with an established diagnosis of dementia according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, criteria for research17 or who showed signs of cognitive impairment (as evidenced by a Mini Mental State Examination MMSE;18 score of 23 or less) were excluded. Additional exclusion criteria included current psychiatric disorder, current hazardous or harmful alcohol consumption,19 or a medical condition that could compromise participation in the study tasks (such as sensory impairment) or reduce medium-term survival (e.g., advanced cancer). Individuals who reported a clinical history of stroke associated with permanent disability were also excluded. One hundred sixty adults met criteria and attended a baseline assessment prior to being randomized into either the CATS or the control Education group. The human research ethics committees of the University of Western Australia and of the Royal Perth Hospital approved this study and all participants provided written informed consent. Procedures of this study followed the principles of the Declaration of Helsinki for Human Rights. Outcome Measures and Timeline of the Study Further assessments post baseline occurred at 10 weeks, 52 weeks, and 104 weeks. The primary outcome measure was the Cambridge Cognitive Examination
Am J Geriatr Psychiatry
-:-, -
2014
Vidovich et al.
TABLE 1. Outline of the Assessments and Timelines of the PACE Trial Clinical Screen
Baseline
10 weeks
52 weeks
104 weeks
Outcome Measure
PHQ-9 (36)
X
X
X
X
X
Mood
CERAD (16)
X
X
X
Global Cognition
MMSE (18)
X
X
X
Global Cognition
AUDIT (19)
X
X
X
Alcohol Use
SAILS (37)
X
X
X
Functional Ability
MHQ CAMCOG-R (20)
X
Assessment Tool
X
X
X X
X X
Health Issues Global Cognition
CVLT-II (21)
X
X
X
X
Memory
Digit Span (22)
X
X
X
X
Attention
Symbol Search (22)
X
X
X
X
Processing Speed
TMTA (23)
X
X
X
X
Attention/Proc. Speed
TMTB (23)
X
X
X
X
Executive Functions
COWAT (23)
X
X
X
X
Executive Functions
LAQ (2) PAQ (38) SNSQ (39)
X X X
X X X
X X X
X X X
Leisure Activity Physical Activity Social Activity
MFQ (40)
X
X
X
X
Perception of Memory
QOL-AD (41)
X
X
X
X
Quality of Life
Measure/Comment Total Score (0e27) Y Scores ¼ [ Mood Individual Subtest Scores [ Scores ¼ [ Performance Total Score (0e30) [ Scores ¼ [ Performance Total Score (0e40) Y Scores ¼ Y Consumption Total Score (0e150) [ Scores ¼ [ Performance Yes or No Total Score (0e105) [ Scores ¼ [ Performance Recall Scores [ Scores ¼ [ Performance Total Scores [ Scores ¼ [ Performance Total Score (0e60) [ Scores ¼ [ Performance Total Time (seconds) Y Scores ¼ [ Performance Total Time (seconds) Y Scores ¼ [ Performance Total Score [ Scores ¼ [ Performance Rarely or Frequently Active (2.5 hrs) or Inactive (
