Recruitment methods and yield rates for a multisite clinical trial exploring risk reduction for Alzheimer's disease (rrAD).

INTRODUCTION: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease. METHODS: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion. RESULTS: Initially, 3290 individuals were screened, of whom 28% were eligible to consent, 805 consented to participate (87.2% of those eligible), and 513 (36.3% of those consented) were randomized. Emails sent from study site listservs/databases yielded the highest amount (20.9%) of screened individuals. Professional referrals from physicians yielded the greatest percentage of consented individuals (57.1%). Referrals from non-professional contacts (ie, friends, family; 75%) and mail/phone contact from a site (73.8%) had the highest yield of randomization. DISCUSSION: Professional referrals or email from listservs/registries were most effective for enrolling participants. The greatest yield of eligible/randomized participants came from non-professional and mail/phone contacts. Future trials should consider special efforts targeting these recruitment approaches. Highlights: Clinical trial recruitment is commonly cited as a significant barrier to advancing our understanding of cognitive health interventions.The most cited referral source was email, followed by interviews/editorials on the radio, television, local newspapers, newsletters, or magazine articles.The referral method that brought in the largest number of contacts was email but did not result in the greatest yield of consents or eligible participants.The sources that yielded the greatest likelihood of consent were professional referrals (ie, physician), social media, and mail/phone contact from study site.The greatest yield of eligible/randomized participants came from non-professional contacts and mail/phone contact from a site.Findings suggest that sites may need to focus on more selective referral sources, such as using contact mailing and phone lists, rather than more widely viewed recruitment sources, such as social media or TV/radio advertisements.

COMbined Exercise Trial (COMET) to improve cognition in older adults: Rationale and methods.

Substantial evidence suggests physical exercise may sustain cognitive function and perhaps prevent Alzheimer's Disease (1, 2). Current public health recommendations call for older adults to do at least 150 min a week of aerobic exercise (e.g. walking) and twice a week resistance exercise (e.g. weight lifting) for physical health. Yet, much remains unknown about how these exercise modalities support brain health independently or in combination. The COMbined Exercise Trial (COMET) is designed to test the combined and independent effects of aerobic and resistance training specifically focusing on exercise-related changes in 1) cognitive performance, 2) regional brain volume, 3) physical function, and 4) blood-based factors. To explore these questions, we will enroll 280 cognitively normal older adults, age 65-80 years, into a 52-week community-based exercise program. Participants will be randomized into one of four arms: 1) flexibility/toning- control 2) 150 min of aerobic exercise only, 3) progressive resistance training only, or 4) combined aerobic and progressive resistance training. Outcomes assessed include a comprehensive cognitive battery, blood biomarkers, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. COMET will provide rigorous randomized controlled trial data to understand the effects of the most common exercise modalities, and their combination (i.e., the standard public health recommendation), on brain health.

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer's: A 1-year randomized controlled trial.

BACKGROUND: Our goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer's-related pathology. We assessed the effect of 52 weeks of a supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging. METHODS AND FINDINGS: This 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs. education control intervention. A total of 117 underactive older adults (mean age 72.9 [7.7]) without evidence of cognitive impairment, with elevated (n = 79) or subthreshold (n = 38) levels of cerebral amyloid were randomized, and 110 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. We conducted 18F-AV45 PET imaging of cerebral amyloid and anatomical MRI for whole brain and hippocampal volume at baseline and Week 52 follow-up to index brain health. Neuropsychological tests were conducted at baseline, Week 26, and Week 52 to assess executive function, verbal memory, and visuospatial cognitive domains. Cardiorespiratory fitness testing was performed at baseline and Week 52 to assess response to exercise. The aerobic exercise group significantly improved cardiorespiratory fitness (11% vs. 1% in the control group) but there were no differences in change measures of amyloid, brain volume, or cognitive performance compared to control. CONCLUSIONS: Aerobic exercise was not associated with reduced amyloid accumulation in cognitively normal older adults with cerebral amyloid. In spite of strong systemic cardiorespiratory effects of the intervention, the observed lack of cognitive or brain structure benefits suggests brain benefits of exercise reported in other studies are likely to be related to non-amyloid effects. TRIAL REGISTRATION: NCT02000583; ClinicalTrials.gov.

A randomized trial using telehealth technology to link caregivers with dementia care experts for in-home caregiving support: FamTechCare protocol.

The number of persons with dementia (PWD) in the United States is expected to reach 16 million by 2050. Due to the behavioral and psychological symptoms of dementia, caregivers face challenging in-home care situations that lead to a range of negative health outcomes such as anxiety and depression for the caregivers and nursing home placement for PWD. Supporting Family Caregivers with Technology for Dementia Home Care (FamTechCare) is a multisite randomized controlled trial evaluating the effects of a telehealth intervention on caregiver well-being and PWD behavioral symptoms. The FamTechCare intervention provides individualized dementia-care strategies to in-home caregivers based on video recordings that the caregiver creates of challenging care situations. A team of dementia care experts review videos submitted by caregivers and provide interventions to improve care weekly for the experimental group. Caregivers in the control group receive feedback for improving care based on a weekly phone call with the interventionist and receive feedback on their videos at the end of the 3-month study. Using linear mixed modeling, we will compare experimental and control group outcomes (PWD behavioral symptoms and caregiver burden) after 1 and 3 months. An exploratory descriptive design will identify a typology of interventions for telehealth support for in-home dementia caregivers. Finally, the cost for FamTechCare will be determined and examined in relation to hypothesized effects on PWD behavioral symptoms, placement rates, and caregiver burden. This research will provide the foundation for future research for telehealth interventions with this population, especially for families in rural or remote locations.

Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial.

BACKGROUND: There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer's disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. METHODS AND FINDINGS: This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control intervention in individuals with early AD. A total of 76 well-characterized older adults with probable AD (mean age 72.9 [7.7]) were enrolled and 68 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. Neuropsychological tests and surveys were conducted at baseline,13, and 26 weeks to assess memory and executive function composite scores, functional ability (Disability Assessment for Dementia), and depressive symptoms (Cornell Scale for Depression in Dementia). Cardiorespiratory fitness testing and brain MRI was performed at baseline and 26 weeks. Aerobic exercise was associated with a modest gain in functional ability (Disability Assessment for Dementia) compared to individuals in the ST group (X2 = 8.2, p = 0.02). There was no clear effect of intervention on other primary outcome measures of Memory, Executive Function, or depressive symptoms. However, secondary analyses revealed that change in cardiorespiratory fitness was positively correlated with change in memory performance and bilateral hippocampal volume. CONCLUSIONS: Aerobic exercise in early AD is associated with benefits in functional ability. Exercise-related gains in cardiorespiratory fitness were associated with improved memory performance and reduced hippocampal atrophy, suggesting cardiorespiratory fitness gains may be important in driving brain benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01128361.

Feasibility of a Memory Clinic-Based Physical Activity Prescription Program.

BACKGROUND: Effective programs for promoting physical activity are needed for those with cognitive impairment. OBJECTIVE: To test the feasibility of mobile Health (mHealth) technology-supported physical activity prescription from a tertiary care memory clinic. METHODS: This feasibility study was designed as a 16-week randomized, crossover trial of a physical activity prescription: 8 weeks of intervention, 8 weeks of baseline or maintenance phase data collection. We recruited 2 cohorts: 21 individuals with Alzheimer-related cognitive impairment (mean age 72.3 (5.2), 9 females), and 9 individuals with normal cognition (mean age 69.6 (5.8), 8 females). We gave each cohort an mHealth accelerometer-based physical activity prescription to double number of steps taken. Our primary outcomes were feasibility and safety. Our secondary outcomes were change in weekly steps taken, Dementia Quality of Life Scale, Self-efficacy Scale, 6-minute Walk, and mini-Physical Performance Test. RESULTS: Set-up and use of the device was not a barrier to participation. However, only 62% of participants with cognitive impairment completed the intervention. The cohort with cognitive impairment did not change their weekly step count above Week 1. All participants in the cohort with normal cognition were able to set up and use their device and increased their weekly step count above Week 1. There were no differences between Week 1 and Week 8 for any secondary measures in either cohort. CONCLUSIONS: Setup and daily use of mHealth technology appears to be feasible for a person with cognitive impairment with the help of a partner, but increasing daily step counts over 8 weeks was not achieved. Future work needs to assess alternative activity prescription goals or additional support for patients and their partners.

Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial.

UNLABELLED: Epidemiological studies suggest a dose-response relationship exists between physical activity and cognitive outcomes. However, no direct data from randomized trials exists to support these indirect observations. The purpose of this study was to explore the possible relationship of aerobic exercise dose on cognition. Underactive or sedentary participants without cognitive impairment were randomized to one of four groups: no-change control, 75, 150, and 225 minutes per week of moderate-intensity semi-supervised aerobic exercise for 26-weeks in a community setting. Cognitive outcomes were latent residual scores derived from a battery of 16 cognitive tests: Verbal Memory, Visuospatial Processing, Simple Attention, Set Maintenance and Shifting, and Reasoning. Other outcome measures were cardiorespiratory fitness (peak oxygen consumption) and measures of function functional health. In intent-to-treat (ITT) analyses (n = 101), cardiorespiratory fitness increased and perceived disability decreased in a dose-dependent manner across the 4 groups. No other exercise-related effects were observed in ITT analyses. Analyses restricted to individuals who exercised per-protocol (n = 77) demonstrated that Simple Attention improved equivalently across all exercise groups compared to controls and a dose-response relationship was present for Visuospatial Processing. A clear dose-response relationship exists between exercise and cardiorespiratory fitness. Cognitive benefits were apparent at low doses with possible increased benefits in visuospatial function at higher doses but only in those who adhered to the exercise protocol. An individual's cardiorespiratory fitness response was a better predictor of cognitive gains than exercise dose (i.e., duration) and thus maximizing an individual's cardiorespiratory fitness may be an important therapeutic target for achieving cognitive benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01129115.

A community-based approach to trials of aerobic exercise in aging and Alzheimer's disease.

The benefits of exercise for aging have received considerable attention in both the popular and academic press. The putative benefits of exercise for maximizing cognitive function and supporting brain health have great potential for combating Alzheimer's disease (AD). Aerobic exercise offers a low-cost, low-risk intervention that is widely available and may have disease modifying effects. Demonstrating that aerobic exercise alters the AD process would have enormous public health implications. The purpose of this paper is to report the protocol of a current, community-based pilot study of aerobic exercise for AD to guide future investigation. This manuscript provides 1) an overview of possible benefits of exercise in those with dementia, 2) a rationale and recommendations for implementation of a community-based approach, 3) recommendation for implementation of similar study protocols, and 4) unique challenges in conducting an exercise trial in AD.

Measuring height without a stadiometer: empirical investigation of four height estimates among wheelchair users.

OBJECTIVE: : This study aimed to compare four methods of measuring or estimating height among wheelchair users, to determine whether these methods result in significantly different estimates, and to determine which method is most accurate. DESIGN: : Height data were obtained for 141 wheelchair users. Height estimates included asking for self-report and measuring recumbent length, knee height, and armspan. All analyses were conducted separately for men and women. A two-group confirmatory factor analysis assessed which measure provided the best estimate of height in this population. It also tested the measurement invariance of the four height estimates between men and women and whether there were significant differences across these estimates within each sex. RESULTS: : Confirmatory factor analysis findings indicated that the four measures yielded significantly different height estimates and body mass index values for both men and women. For both sexes, armspan resulted in the longest estimate, and measured recumbent length resulted in the shortest, with the reverse pattern for body mass index values. The common variance estimates were outstanding for recumbent length (92%) and knee height (>83%) and were very good for self-report (>75%), whereas the common variance for armspan was poor (<42%). CONCLUSIONS: : The measurement method used to estimate height yields significantly different values for both height and body mass index among wheelchair users who cannot stand to be measured using a stadiometer. Recumbent length yields the most accurate height estimate for wheelchair users. However, when logistical and practical considerations pose difficulties for obtaining this measure, height estimates based on knee height and self-report may provide reasonable alternatives.

Safety considerations when promoting exercise in individuals with serious mental illness.

Histories and physical exams, completed prior to starting a weight loss program, showed that 52% (N=106) had high risk for coronary artery disease (CAD), 40% had difficulty performing a tandem gait (indicator of balance), and 30% had an existing musculoskeletal disorder. These risks are realistic concerns when recommending exercise and/or walking.

A psychiatric rehabilitation approach to weight loss.

Obesity is a major problem nationwide and even more prevalent among people with psychiatric disabilities. This study examined the efficacy of a psychiatric rehabilitation weight loss program. Twenty-one individuals participated in the 12-week intervention. Another 15 individuals served as matched controls. Results indicate the intervention group improved more than the control group for weight, body mass index, waist circumference and physical activity. The intervention group lost 2.7 kg (6 lbs) and the control group gained 0.5 kg (1 lb). A weight loss program incorporating psychiatric rehabilitation principles was effective for people with psychiatric disabilities at a community based program.