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Trial registered on ANZCTR


Registration number
ACTRN12614000223639
Ethics application status
Approved
Date submitted
25/02/2014
Date registered
3/03/2014
Date last updated
3/03/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of physical and mental training on cognition and Alzheimer's disease biomarkers
Scientific title
Effects of Physical Activity and Cognitive Stimulation on
Cognitive Functioning, Alzheimer’s Disease Related
Blood Biomarkers and Brain Glucose Metabolism in
Older Adults
Secondary ID [1] 284158 0
Nil
Universal Trial Number (UTN)
U1111-1153-8234
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preventing or Delaying the onset of Cognitive decline 291249 0
Preventing or Delaying the onset of Alzheimer's disease 291250 0
Condition category
Condition code
Mental Health 291593 291593 0 0
Other mental health disorders
Neurological 291594 291594 0 0
Alzheimer's disease
Neurological 291595 291595 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 - Physical Activity - walking for 3 days a week for 60 minutes for 16 weeks; resistance training using ankle weights and gymsticks for 40-60 minutes per day for 2 days a week for 16 weeks. Training provided by exercise physiologists in the 60 minute group specific monthly meetings and at the time of their personal physical fitness assessment. The participants then performed these activities on their own at home.

As walking was considered to be the main component of exercise, a pedometer was given to each subject to record number of steps during the intervention period. Moreover, the Borg's scale was used to measure the level of perceived exertion for each participant. The intervention group recorded the Borg's scale in their daily logbooks as well as was assessed during their physical fitness assessments. Thus participants were advised in the 60-minute monthly group meeting for 4 months to gradually increase their activities based on the level of their perceived excretion. This gradual increase was recorded by exercise physiologist in the log book for the next four weeks at every monthly group meeting for each participant. Similar procedure of gradual increment from baseline was followed for resistance training exercises which was assessed using 1 Repetition Maximum (1RM).


Arm 2 - Cognitive Stimulation - auditory and visual stimulation using computerized software programs - 60 minutes for 5 days a week for 16 weeks. The Brain fitness Program (Posit Science, USA) for auditory stimulation and the Insight program (Posit Science, USA) for visual stimulation was used for training. Half of the participants started with the auditory program for the first 8 weeks followed by the visual training program for the last 8 weeks and vice versa for the remaining participants in the group. Training and problem solving occurred in the 60 minute group specific monthly meetings for 4 months. The participants installed the software's and performed these exercises on their personal computers at home.

Arm 3 - Combination of Arm 1 and Arm 2



Printed instructions handouts were given to all intervention groups explaining their respective physical/mental exercises. All the participants were monitored for their adherence in fortnightly phone calls, monthly group meetings and log books that recorded the intervention activities as well as routine lifestyle physical and mental activities for 16 weeks.
Intervention code [1] 288854 0
Lifestyle
Intervention code [2] 288855 0
Prevention
Comparator / control treatment
Control group - No treatment/education given; continued with their routine lifestyle activities;

Participants gained education regarding the physical and mental training arm of the study from the general participant information sheet, fellow volunteers in the intervention groups coming in on the same day of their various assessments and word of mouth regarding the beneficial effects of lifestyle activities on cognition.
Control group
Active

Outcomes
Primary outcome [1] 291540 0
Cognition

1. Cambridge Cognitive Assessment - revised (CAMCOG-R). MMSE is a part of CAMCOG-R
2. Cambridge Contextual Reading Test (CCRT)
3. Rey auditory verbal learning test (RAVLT)
4. Controlled oral word association test (COWAT)
5. Cogstate computerized battery

Questionnaire - memory functioning questionnaire, short form 36 , international physical activity questionnaire, hospital anxiety and depression scale
Timepoint [1] 291540 0
Baseline, 8 weeks mid intervention and at 16 weeks on completion of the intervention
and at 52 weeks from baseline visit
Secondary outcome [1] 307011 0
Blood Biomarkers
plasma homocysteine, serum cortisol, serum insulin, lipid profile
(plasma cholesterol, triglycerides, high and low density lipoprotein), plasma beta amyloid 40 and 42 and plasma BDNF.

APOE genotyping will also be performed.
Timepoint [1] 307011 0
Baseline, 8 weeks mid intervention and at 16 weeks on completion of the intervention
Secondary outcome [2] 307012 0
FDG PET scan on randomly selected participants from each group. Not all participants underwent FDG PET scans

To assess cerebral glucose metabolism
Timepoint [2] 307012 0
Baseline and / or at 16 weeks on completion of the intervention
Secondary outcome [3] 307013 0
Physical fitness assessments

1. Borgs scale
2. Incremental Shuttle walk test
3. 1 RM

baseline physical activity levels assessed by actigraphs for 7 days given to each study participant before the start of the intervention
Timepoint [3] 307013 0
Baseline, 8 weeks mid intervention and at 16 weeks on completion of the intervention
Secondary outcome [4] 307030 0
DXA scan to assess body composition on randomly selected participants from each group. Not all participants underwent DXA scans.
Timepoint [4] 307030 0
Baseline and at 16 weeks on completion of the intervention

Eligibility
Key inclusion criteria
1. Mini Mental State Examination (MMSE) greater than or equal to 24.
2. Personal physician fitness certificate stating that the participant is fit to take part in a home based physical exercise intervention program.
Minimum age
60 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Diagnosis of any type of dementia including AD.
2. Uncontrolled medical condition–physical or mental that could lead to difficulty complying with the protocol including history of myocardial infarction, unstable or severe cardiovascular disease including angina or congestive heart failure, schizophrenia, bipolar disorder, anxiety neurosis or depression.
3. Arthritis causing any disability or restricted movements.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants were partially randomized over the phone and some were also allocated into the participant preferred group
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample size of at least 50 subjects in each group will be required to detect change in cognitive outcomes between the groups at 85% power and a 5% significance level along with a medium effect size. Dropouts will be replaced by new recruitment.

The data was analysed using various statistical methods to test the specific hypotheses of the study. Baseline categorical data associations with group assignment were
assessed using Chi-squared test to ensure that the groups were comparable with respect to these variables, whereas the continuous data was analysed using one-way ANOVA.
The cognitive scores, biomarkers and FDG-PET, DXA data from the 4 groups was compared using General Linear Model procedure in IBM SPSS Version 19. The pretraining values were used as a covariate in the analysis. Other covariates that were included were age, sex, education, APOE e4 status. Post-hoc comparison of means was only performed if the overall treatment comparison in the analysis of variance was significant and when an overall group x time interaction was significant. P-values less than 0.05 were considered as statistically significant. The residuals from the analyses were assessed to ensure that the assumptions of the General Linear Model procedure were satisfied. Where the assumptions were not satisfied, an appropriate non-parametric equivalent statistical test was used. Baseline correlations, where appropriate, were performed between the various measures using Spearman’s correlation coefficient.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
9/07/2009
Actual
9/07/2009
Date of last participant enrolment
Anticipated
26/08/2010
Actual
26/08/2010
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 2142 0
Hollywood Private Hospital - Nedlands
Recruitment postcode(s) [1] 7822 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 288785 0
University
Name [1] 288785 0
University of Western Australia; Australian Postgraduate award
Country [1] 288785 0
Australia
Funding source category [2] 288786 0
Charities/Societies/Foundations
Name [2] 288786 0
McCusker Alzheimer's Research Foundation
Country [2] 288786 0
Australia
Funding source category [3] 288789 0
Other
Name [3] 288789 0
Freemasons of Western Australia Education Grant
Country [3] 288789 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
McCusker Alzheimer's Research Foundation
Address
Suite 22, Hollywood Medical Centre,
85 Monash Avenue
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 287487 0
University
Name [1] 287487 0
University of Western Australia
Address [1] 287487 0
35 Stirling Highway, Crawley WA 6009
Country [1] 287487 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290630 0
Human Research Ethics Committee at UWA
Ethics committee address [1] 290630 0
The University of Western Australia (M459)
35 Stirling Highway, Crawley WA 6009
Ethics committee country [1] 290630 0
Australia
Date submitted for ethics approval [1] 290630 0
Approval date [1] 290630 0
13/10/2010
Ethics approval number [1] 290630 0
RA/4/1/4472 (External Approval)
Ethics committee name [2] 290631 0
Human Research Ethics Committee of Edith Cowan University
Ethics committee address [2] 290631 0
270 Jonndalup Drive
Joondalup WA 6027
Ethics committee country [2] 290631 0
Australia
Date submitted for ethics approval [2] 290631 0
Approval date [2] 290631 0
07/07/2009
Ethics approval number [2] 290631 0
3286
Ethics committee name [3] 290632 0
Hollywood Private Hospital Research Ethics Committee
Ethics committee address [3] 290632 0
85 Monash Avenue,
Hollywood Private Hospital
Nedlands WA 6009
Ethics committee country [3] 290632 0
Australia
Date submitted for ethics approval [3] 290632 0
Approval date [3] 290632 0
07/07/2009
Ethics approval number [3] 290632 0
HPH279

Summary
Brief summary
Evidence is now emerging to suggest that lifestyle factors, namely physical activity and cognitive stimulation could provide a cost-effective and relatively simple means of protecting the brain against age-related cognitive decline and dementia. This hypothesis can generally be described as a “use it or lose it” philosophy. However, it is unclear which forms, intensity and frequency of physical activity provide the most benefit. Similarly, the optimal level and form of cognitive stimulation remains to be determined. To date, very few intervention studies have demonstrated improvement through standardized tests of memory and cognition (neuropsychological tests) and none have used blood biomarkers as part of the assessment criteria. Therefore, this study is specifically designed to determine whether a home-based lifestyle intervention program, involving physical activity or cognitive stimulation alone, or in combination, can provide measurable improvements in cognition and AD-related blood biomarkers amongst the healthy, community-dwelling elderly.
200 male and female participants aged 60 to 85 will be recruited into 4 intervention groups: physical activity alone, cognitive stimulation alone, physical activity and cognitive stimulation combined or a control group. The intervention period for all of the groups will last for 16 weeks. Participants will be monitored closely throughout the intervention period and assessed at baseline (pre-intervention), during the intervention at 8 weeks and at 2 post-intervention time-points (16 and 52 weeks). The assessment criteria include a battery of neuropsychological and clinical tests and measurement of AD-related blood biomarkers. 20% of participants will undergo a brain imaging scan and body composition analysis to assess the effect of the intervention on brain activity and changes in fat and lean body mass.
This project will provide greater insight into the mechanisms underlying the protective effect of physical activity and cognitive stimulation on brain function. The project will also directly assess and compare the efficacy of home-based intervention strategies on a wide range of parameters. Should the interventions prove successful, this study could then be expanded to include a greater number of participants and assess multiple strategies with the ultimate aim being the development of a public health strategy for the prevention/delay of cognitive decline.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 46522 0
Dr Tejal Shah
Address 46522 0
McCusker Alzheimer's Research Foundation
Suite 22, Hollywood Medical Centre,
85 Monash Avenue, Nedlands WA 6009
Country 46522 0
Australia
Phone 46522 0
+61 8 93474211
Fax 46522 0
Email 46522 0
[email protected]
Contact person for public queries
Name 46523 0
Tejal Shah
Address 46523 0
McCusker Alzheimer's Research Foundation
Unit 2/142 Stirling Highway
Nedlands WA 6009
Country 46523 0
Australia
Phone 46523 0
+61 8 63043955
Fax 46523 0
Email 46523 0
[email protected]
Contact person for scientific queries
Name 46524 0
Tejal Shah
Address 46524 0
McCusker Alzheimer's Research Foundation
unit 2/142 Stirling highway
Nedlands WA 6009
Country 46524 0
Australia
Phone 46524 0
+61 8 63043955
Fax 46524 0
Email 46524 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



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