BACKGROUND:Resilience is the capacity of an organism to both resist and recover from stressors, and its decline can be an early indicator of susceptibility that precedes frailty, disability, and death. This study explores the use of provocative tests - time-based responses to non-harmful challenges - as potential indicators of resilience. METHODS:Provocative tests were performed in 50 community-dwelling adults (24 men, 26 women), aged 23-82 years and included cognitive challenges, strength and heart rate recovery after exercise, cold exposure, blood occlusion, and resistance to balance perturbations. RESULTS:Age was associated with declines in recovery from cold-water hand immersion (r2 = 0.18, P = 0.002) and upper-arm blood occlusion (r2 = 0.11, P = 0.023). Susceptibility to balance perturbations also increased with age (r2 = 0.10, P = 0.025). Notably, heart rate and strength recovery post-exercise did not correlate with age, although older participants walked shorter distances (r2 = 0.54, P < 0.0001) and curled less weight (r2 = 0.17, P = 0.0003). Cognitive performance in the Stroop Color and Word test was unaffected by exercise but did show age-related declines (r2 = 0.53, P < 0.0001). A composite resilience score derived from the measures inversely associated with age (r2 = 0.17, P = 0.0027). Additionally, responses to cold-water immersion and blood occlusion correlated in older adults (r2 = 0.31, P = 0.002, n = 18), suggesting interrelated physiological responses. CONCLUSIONS:These findings support provocative testing to identify early signs of declining resilience and guide interventions targeting age-related vulnerability.

The health care system is insufficiently capitalizing on the benefits of physical exercise in America's aging population. Few tools exist to help clinicians incorporate physical activity into their clinical care, and barriers limit older adults from initiating and maintaining exercise programs. The Lifestyle Empowerment for Alzheimer's Prevention (LEAP! Rx) Program has been designed to support providers and participants in lifestyle change. LEAP! Rx uses two forms of participant enrollment: physician referrals through electronic health records and self-referrals to test the efficacy of delivering a community-based exercise and healthy lifestyle program to older adults. After referral into the program, participants are randomized to receive the LEAP! Rx Program or are placed in a standard-of-care group to receive the program later. The LEAP! Rx program consists of a personalized and structured exercise program, lifestyle education, and mobile health monitoring. This includes a 12-week Empowerment phase with coaching and supervised exercise training, followed by a 40-week Lifestyle phase with intermittent supervised exercise and coaching. Lifestyle education includes monthly, evidence-based classes on optimal aging. The evaluation of LEAP! Rx focuses on 1) the assessment of implementation and scalability of the LEAP!Rx Program for clinicians and patients 2) the effect of the LEAP! Rx Program on cardiorespiratory fitness, 3) the impact of the LEAP! Rx Program on secondary intervention outcome measures of chronic disease risk factors, including insulin resistance, body composition, and lipids. If successful, this study's findings could advance future healthcare practices, providing a new and practical approach to aging and chronic disease prevention.

Abstract 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.

Clinicians have few tools to incorporate physical activity into clinical care to capitalize on the benefits of exercise for Alzheimer’s prevention. Barriers limit older adults from initiating and maintaining exercise recommendations. We tested the efficacy of an exercise and healthy lifestyle program, LEAP! Rx, in physician-referred patients vs. self-referred patients (typical referral method). Physician referrals occurred via electronic prescription embedded in the electronic health record. The program included 12 weeks of regular supervised exercise at a network of YMCAs, followed by 40 weeks of intermittent supervised exercise. Participants were offered monthly Alzheimer’s prevention classes (diet, cognitive engagement, stress reduction). An RCT tested efficacy of LEAP! Rx for gains in cardiorespiratory fitness and reduced disease markers. Participants (age 65+) were randomized to the Intervention Group (n = 110) or a Control Group (n = 110). 54% were referred by physicians, 46% were self-referred. During the pandemic, exercise coaching was moved online. We analyzed increases in cardiorespiratory fitness (VO2max) and changes in insulin resistance, body composition, and lipids between baseline and week 12. Analyses are based on 179 participants’ data at week 12. The intervention group increased 3.6% in cardiorespiratory fitness (VO 2 max ml/kg/min) vs. 1.0% in Controls (non-significant trend, t = 1.66, p = .098). The intervention group reduced fat mass by 2.0% vs. 0.7% in Controls (non-significant trend, t = 0.163, p = .105). Self-referred participants increased 4.7% in VO2max (p = .007) vs. 2.0% in physician-referred (p = 0.20). Both referral groups had reductions in fat mass (p<.05). Adherence was lower in physician-referred (fewer aerobic goals met (p = .038), more weeks of pandemic-related gym closures (p<.001)). Physician-referred had more participants identifying as Black and Latino/a (22%) vs. self-referred (8%). Although outcomes improved across 12 weeks, we found no significant differences between intervention and control groups. A potential explanation is differences between physician-referred and self-referred groups. Our unique physician referral method resulted in a more racially/ethnically diverse sample. However, the physician-referred group had fewer VO2 gains, likely due to greater pandemic-related adherence disruption. When week 52 is complete, we will investigate feasibility and acceptability of the referring physicians’ role and analysis of actigraphy data to clarify mechanisms of differential benefits.

Exercise and Intensive Vascular Risk Reduction in Preventing Dementia (rrAD Study) was a NIH-funded multisite, clinical trial. The rrAD Study assesses the effects of aerobic exercise training and intensive pharmacological reduction of vascular risk factors on cognitive performance in older adults at high risk for Alzheimer’s disease (AD). The enrollment goal was 640 participants across the span of two years. We report herein our recruitment and enrollment results of the rrAD Study. The major inclusion criteria were older adults, age 60-85, who had family history (FH) of dementia or subjective memory complaints, hypertension, and a sedentary lifestyle. Individuals with dementia and other neurodegenerative diseases, or unstable medical conditions were excluded (NCT02913664). 3,291 potential participants were recruited and 2,747 were phone screened to participate in the rrAD Study. 513 cognitively normal older adults, aged 60 to 85 years with hypertension and increased risk for AD were randomized. The rrAD Study had a 15.5% recruitment yield of total phone screened individuals to randomization. E-mail brought in the largest number of phone screen contacts and was the overall most cited recruitment source (20.9%, n = 574, Figure 1), followed by interviews/editorials (18.7%, n = 515), other/unknown source (17.9%, n = 492), and broadcast advertising (11.8%, n = 325). E-mail and interview/editorials led to greatest number of consented and randomized participants. However, the recruitment sources that were more likely to lead to consent/participation were, professional referral (i.e. physician, 57.1% yield), social media (49.2% yield), and mail/phone from site (45.2% yield). From this outreach, the utilization of multiple recruitment sources prove to be a dominant factor to meet recruitment and enrollment goals. E-mail and interview/editorials demonstrate to be the most effective recruitment sources that led to the greatest number of phone screens, consents, and randomizations. In future studies, we might limit the broadcast advertisement effort since it did not lead to a high volume of consents and randomization; this could be due to the limited amount of study information stated on a 60-second radio advertisement. Whereas, e-mail and interview/editorials may produce more qualified participants since these sources can provide a wide scope and detailed information about the study.

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.

BackgroundOur 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 findingsThis 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.ConclusionsAerobic 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 registrationNCT02000583; ClinicalTrials.gov.

Exercise and Intensive Vascular Risk Reduction in Preventing Dementia (rrAD Study) is a NIH-funded multicenter randomized controlled trial (RCT) targeting older adults who are at high risk for developing Alzheimer's disease (AD). The original goal of rrAD is to enroll 640 participants in 24 months from January 2017 to January 2019. Development of effective recruitment strategies to meet the enrollment goal in the proposed timeline is essential for the trial success. We reported herein our recruitment experience of the rrAD Study. The major inclusion criteria are older adults, age 60-85, who have family history (FH) of dementia or subjective memory complaints, hypertension, and a sedentary lifestyle. Individuals with dementia and other neurodegenerative diseases, stroke, or unstable medical conditions are excluded (NCT02913664). Recruitment strategies in rrAD are diversified including mainly professional and non-professional referral, recruitment from the existing database at the sites, community outreach, advertisements through traditional media (local newspapers, TV and radio stations) and digital media (internet and social media), and study material (brochures, flyers, handouts, postcards, etc.). By the end of 2018, the study has performed phone screening in 2,636 individuals and randomized 321 participants in the study arms (12% yield). Media (traditional and digital), database, and referral together produced the largest number of interested individuals (71%). The major reasons for phone screening failure were blood pressure (BP) and lack of FH of dementia or subjective memory complaints. Media, database, and referral together also yielded the highest randomized subjects (83%) (Table 1). The major reasons for clinical screening failure were BP, clinical conditions, and willingness for randomization.

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.

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

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 de signed 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.

Mobile health (mHealth) technologies have been rapidly adopted by the public over the last 5 years as a means to measure and share health information socially. mHealth technologies are also being adopted in the healthcare community to record positive health behaviors, though their utility is unclear in the dementia population. We sought to administer a physical health prescription using mHealth technology (Internet connected pedometer). The goal was to double the number of steps taken over 8 weeks. We enrolled 15 individuals with mild dementia seen on an outpatient basis in our memory care clinic. Each was prescribed a pedometer and a weekly step goal and helped to connect the pedometer to an online account that was monitored by study staff. Participants were called every 2 weeks or more frequently if the were not wearing their pedometer. Seven individuals withdrew from the study. In the remaining individuals, compliance with wearing the device was high. Three monitors were lost. However, as a group, participants were unable to meet weekly step goals and did not increase their physical activity over the 8 weeks of the study. Weekly steps at follow-up were 90% of baseline. Only 2 individuals increased their step counts (mean change 53%). We conclude that the use of mHealth technology such as small, internet-connected pedometers is feasible for individuals with mild dementia, but that additional support beyond a written prescription and telephone encouragement is necessary to increase physical activity.

with FAST 5 to 7G, 75% in use of anticholinesterase, 16.7% died in the household and 77% in hospital. Caregivers had on average age 61.4 6 13.9 years, 79.5% women and 65.9% child (a). The prevalence of prolonged grief in caregivers occurred in 11.4%. Decreased risk of Mourning Extended when the son was who provided care (OR: 0.032; 95% CI: 0.001 to 0.905; p 1⁄4 0.044). There was an increased risk of Mourning Extended caregivers interested in counseling (OR: 17.838; 95% CI: 1.302 to 244.39, p 1⁄4 0.031). Conclusion: It is important that caregivers have a targeted assessment and psychological support before and after death of patients with advanced dementia to prevent Prolonged grief. Further research may help to identify and direct them to specialized professional help.

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

Increasing evidence suggests that aerobic exercise positively impacts the brain. Animal studies suggest aerobic exercise stimulates neurogenesis. Little data exists in humans with Alzheimer's disease (AD) although we previously reported a cross-sectional association between aerobic fitness levels and whole brain (Burns et al. 2008; Honea et al. 2009) and hippocampal atrophy (Vidoni et al. 2012) in individuals with early AD. We present preliminary neuroimaging results from a community-based randomized controlled trial, the Alzheimer's Disease Exercise Program Trial (ADEPT), details for which have been published elsewhere (Vidoni et al. 2012). One major goal was to assess effects of exercise on global and hippocampal brain volume change over 6 months. Participants were randomized to 6 months of non-aerobic activities (control arm) or aerobic exercise (150 minutes a week). Brain MRI (Siemens 3.0 Tesla MRI scanner) was obtained at baseline and at 6 months. MRI scans was checked for image artifacts and anatomical abnormalities and n=43 participants had adequate data at two time points. Cortical reconstruction and volumetric segmentation was performed with the longitudinal stream of the Freesurfer image analysis suite (Reuter et al., 2012). Percent change from baseline to 6 months was calculated for bilateral hippocampal volume and total gray matter volume. The aerobic exercise (n= 22) and control (n=21) groups were not different in age, sex, MMSE (mean exercise group was 26.7, mean controls was 25.5), body mass index, and dementia severity (Clinical Dementia Rating). Hippocampal atrophy rate was reduced in those in the aerobic exercise group (-0.16% [2.4]) compared to those in the control arm (-2.08% [2.5], p=0.045). There were no differences in change in gray matter volume between groups (p=.784).

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.

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.

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.