Background With aging and injury, females experience ectopic redistribution of appendicular adipose tissue (AAT) into the visceral compartment, where adipose tissue (VAT) becomes highly inflammatory and increases risk of reinjury and chronic illness. Therefore, strategies that can disrupt this unhealthy adipose redistribution after hip fracture injury are of great interest. We examined the effects of testosterone therapy on total adipose tissue (TAT) and adipose distribution in older females recovering from hip fracture. Methods This was a sub-analysis of the STEP-HI study, a multi-site randomized clinical trial in which older females recovering from hip fracture were assigned to a 6-month exercise intervention combined with either topical testosterone gel (EX+T, n=35, age=79±9 years) or placebo gel (EX+P, n=31, age=76±7 years). Changes in TAT, AAT, and VAT mass and percentage of TAT in each region (%AAT and %VAT) were measured using dual x-ray absorptiometry, and changes over the 6-month intervention were compared between groups. Results Over the intervention, changes were similar in TAT (EX+P: 298±2002 g, EX+T: 419±2086 g, p=0.810), AAT (EX+P: 52±1007 g, EX+T: 39±1078 g, p=0.810), %AAT (EX+P: -0.42±1.40% of TAT, EX+T: -0.52±1.67% of TAT, p=0.792) and VAT (EX+P: 45±232 g; EX+T: −44±151 g; p=0.073). However, relative changes in %VAT from pre-intervention (EX+P: Δ3.51±18.42%; EX+T: −Δ10.57±17.13%; p=0.004) marked favorable effects of testosterone on relative visceral adiposity. Conclusion While testosterone did not decrease overall adipose stores compared to exercise alone in older females recovering from hip fracture, it did promote a healthy pattern of adipose distribution away from the viscera. Clinical Trial # NCT02938923

Importance Physical inactivity, hypertension, and hyperlipidemia are modifiable cardiovascular risk factors for age-related cognitive decline and dementia. It remains unknown whether exercise training combined with intensive pharmacological reduction of cardiovascular risk factors (IRVR) would have greater benefits on cognitive function than those of exercise or IRVR alone. Objective To determine the effects of exercise, IRVR, and exercise combined with IRVR on cognitive function in older adults. Design, Setting, and Participants This single-blind, multicenter randomized clinical trial with a 2 × 2 factorial design and duration of 24 months was conducted at 4 clinical sites in the US. Enrollment began on February 2, 2017; the final study visit was on January 31, 2022. After screening, older adults without dementia and with hypertension, family history of dementia, and/or self-reported subjective cognitive decline were randomized. Data were analyzed from December 2022 through October 2024. Interventions Participants were randomized with a 1:1:1:1 ratio to aerobic exercise training, IRVR (lowering of systolic blood pressure to <130 mm Hg and serum low-density lipoprotein cholesterol with atorvastatin), IRVR + exercise, and usual care. Main Outcomes and Measures The primary outcome was change in global cognitive function at 24 months from baseline, assessed with the Preclinical Alzheimer Cognitive Composite (PACC) score. Secondary outcomes were changes in the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) fluid composite score and individual test scores. Results A total of 3290 individuals were screened, and 513 older adults (aged 60-85 years) without dementia and with hypertension, family history of dementia, and/or self-reported subjective cognitive decline were randomized. Among 513 randomized participants (mean [SD] age, 68.7 [6.0] years; 323 female participants [63.0%]), 443 completed 24-month visits, and 480 were included in the primary data analysis. For the primary outcome, there were no statistically significant interactions between intervention groups and time of visits ( P = .13). At 24 months, PACC scores increased by 0.2 units in the no-exercise group (95% CI, 0.1-0.3) and by 0.3 units in the exercise group (95% CI, 0.2-0.4), with no significant group differences (0.1 units; 95% CI, −0.1 to 0.2; P = .37). PACC scores also increased by 0.3 units in the no-IRVR group (95% CI, 0.2-0.4) and by 0.2 units in the IRVR group (95% CI, 0.1-0.3), with no significant group differences (0.1 units; 95% CI, −0.3 to 0.03; P = .12). Increases in the NIHTB-CB composite score and individual test scores with exercise or IRVR showed similar results. Conclusions and Relevance In this multicenter randomized clinical trial among older adults with family history of dementia and/or self-reported subjective cognitive decline, exercise, IRVR, or both did not result in statistically significant differences in improvements in cognitive function over 24 months. Trial Registration ClinicalTrials.gov Identifier: NCT02913664

Importance:Physical inactivity, hypertension, and hyperlipidemia are modifiable cardiovascular risk factors for age-related cognitive decline and dementia. It remains unknown whether exercise training combined with intensive pharmacological reduction of cardiovascular risk factors (IRVR) would have greater benefits on cognitive function than those of exercise or IRVR alone. Objective:To determine the effects of exercise, IRVR, and exercise combined with IRVR on cognitive function in older adults. Design, Setting, and Participants:This single-blind, multicenter randomized clinical trial with a 2 × 2 factorial design and duration of 24 months was conducted at 4 clinical sites in the US. Enrollment began on February 2, 2017; the final study visit was on January 31, 2022. After screening, older adults without dementia and with hypertension, family history of dementia, and/or self-reported subjective cognitive decline were randomized. Data were analyzed from December 2022 through October 2024. Interventions:Participants were randomized with a 1:1:1:1 ratio to aerobic exercise training, IRVR (lowering of systolic blood pressure to <130 mm Hg and serum low-density lipoprotein cholesterol with atorvastatin), IRVR + exercise, and usual care. Main Outcomes and Measures:The primary outcome was change in global cognitive function at 24 months from baseline, assessed with the Preclinical Alzheimer Cognitive Composite (PACC) score. Secondary outcomes were changes in the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) fluid composite score and individual test scores. Results:A total of 3290 individuals were screened, and 513 older adults (aged 60-85 years) without dementia and with hypertension, family history of dementia, and/or self-reported subjective cognitive decline were randomized. Among 513 randomized participants (mean [SD] age, 68.7 [6.0] years; 323 female participants [63.0%]), 443 completed 24-month visits, and 480 were included in the primary data analysis. For the primary outcome, there were no statistically significant interactions between intervention groups and time of visits (P = .13). At 24 months, PACC scores increased by 0.2 units in the no-exercise group (95% CI, 0.1-0.3) and by 0.3 units in the exercise group (95% CI, 0.2-0.4), with no significant group differences (0.1 units; 95% CI, -0.1 to 0.2; P = .37). PACC scores also increased by 0.3 units in the no-IRVR group (95% CI, 0.2-0.4) and by 0.2 units in the IRVR group (95% CI, 0.1-0.3), with no significant group differences (0.1 units; 95% CI, -0.3 to 0.03; P = .12). Increases in the NIHTB-CB composite score and individual test scores with exercise or IRVR showed similar results. Conclusions and Relevance:In this multicenter randomized clinical trial among older adults with family history of dementia and/or self-reported subjective cognitive decline, exercise, IRVR, or both did not result in statistically significant differences in improvements in cognitive function over 24 months. Trial Registration:ClinicalTrials.gov Identifier: NCT02913664.

Importance Despite receiving postacute rehabilitation services, many older women with a recent hip fracture repair are unable to return to their prefracture level of function. Whether testosterone therapy can enhance recovery after hip fracture in older women with persistent mobility impairments has not been fully examined. ObjectiveTo evaluate the effects of a supervised exercise program combined with topical testosterone therapy on functional outcomes in older women with a recent hip fracture. Design, Setting, and Participants This phase 3 double-blind, placebo-controlled randomized clinical trial, Starting a Testosterone and Exercise Program After Hip Injury (STEP-HI), was conducted at 8 US sites between December 2018 and August 2023. Participants were women aged 65 years or older with a recent surgical repair of a nonpathologic femur fracture, met objective criteria for mobility impairment, and were community dwelling after discharge from rehabilitation. During the first 14 months of the trial, participants were randomly assigned to 1 of 3 treatment groups: exercise plus topical testosterone gel, exercise plus placebo gel, or enhanced usual care. Statistical analysis, using a modified intention-to-treat approach, was performed from November 2023 to November 2024. Interventions For 24 weeks, the 2 exercise groups underwent a supervised, multimodal high-intensity exercise program that included progressive resistance training with trained and certified exercise interventionists. Testosterone was provided in the form of a topical gel (generic 1.0% testosterone), and the placebo gel was chemically identical but without testosterone. The enhanced usual care group was prescribed a self-administered low-intensity home-based exercise program and a staff-led monthly health education session. Main Outcomes and Measures The primary outcome was the between-group difference in the change in the 6-minute walking distance (6MWD) from baseline to 24 weeks. Results Among the 129 women randomized (54 to the exercise plus testosterone group, 55 to the exercise plus placebo group, and 20 to the enhanced usual care group; mean [SD] age, 79.3 [8.4] years) included in the STEP-HI trial (122 (94.6%) provided primary outcome data for baseline and at least 1 time point (12 or 24 weeks). The mean (SD) change in the 6MWD between baseline and 24 weeks was not significantly different for exercise plus topical testosterone gel (n = 53; 42.7 [8.2] m) compared with exercise plus placebo gel (n = 51; 40.5 [8.4] m) and enhanced usual care (n = 18; 37.7 [14.8] m). Conclusions and Relevance In the STEP-HI randomized clinical trial, supervised exercise training combined with testosterone therapy conducted in older women recovering from a hip fracture did not lead to significant improvement in 6MWD compared with supervised exercise alone. Adding testosterone therapy to exercise may not provide further benefits for long-distance mobility. Whether it can improve physical performance and mobility for short distances in this patient population warrants further study.

Objective Differences in cognitive outcomes for two home-based 16-week interventions after usual rehabilitative care post-hip fracture were examined. Methods Community Ambulation Project randomized controlled trial included 210 hip fracture participants. Interventions: Specific multi-component (PUSH) included strength-, balance-, function-, and endurance-based exercises; non-specific active control (PULSE) included seated range-of-motion exercises and sensory transcutaneous electrical neurostimulation. Cognitive measures: Modified Mini-Mental State Examination, plus Hooper Visual Organization Test and Trails A/B in an ancillary study (CAP-MP, n = 40), assessed pre-randomization and 16 and 40 weeks post-randomization. Results Over 16 weeks, PUSH-assigned participants became faster on Trails A (Δ = −6.3, 95% CI: −16.7, 4.2); those in PULSE became slower (Δ = 9.3, 95% CI: −1.7, 20.3, p = .04). At 40 weeks, PUSH-assigned participants became faster on Trails B (Δ = −21.5, 95% CI: −46.2, 3.3) while those in PULSE became slower (Δ = 15.2, 95% CI: −11.9, 42.3, p = .04). No other significant differences were found. Discussion Results suggest that multi-component exercise interventions like PUSH may prevent/delay decline or improve attention and psychomotor speed in patients with recent hip fracture.

Despite receiving postacute rehabilitation services, many older women with a recent hip fracture repair are unable to return to their prefracture level of function. Whether testosterone therapy can enhance recovery after hip fracture in older women with persistent mobility impairments has not been fully examined. To evaluate the effects of a supervised exercise program combined with topical testosterone therapy on functional outcomes in older women with a recent hip fracture. This phase 3 double-blind, placebo-controlled randomized clinical trial, Starting a Testosterone and Exercise Program After Hip Injury (STEP-HI), was conducted at 8 US sites between December 2018 and August 2023. Participants were women aged 65 years or older with a recent surgical repair of a nonpathologic femur fracture, met objective criteria for mobility impairment, and were community dwelling after discharge from rehabilitation. During the first 14 months of the trial, participants were randomly assigned to 1 of 3 treatment groups: exercise plus topical testosterone gel, exercise plus placebo gel, or enhanced usual care. Statistical analysis, using a modified intention-to-treat approach, was performed from November 2023 to November 2024. For 24 weeks, the 2 exercise groups underwent a supervised, multimodal high-intensity exercise program that included progressive resistance training with trained and certified exercise interventionists. Testosterone was provided in the form of a topical gel (generic 1.0% testosterone), and the placebo gel was chemically identical but without testosterone. The enhanced usual care group was prescribed a self-administered low-intensity home-based exercise program and a staff-led monthly health education session. The primary outcome was the between-group difference in the change in the 6-minute walking distance (6MWD) from baseline to 24 weeks. Among the 129 women randomized (54 to the exercise plus testosterone group, 55 to the exercise plus placebo group, and 20 to the enhanced usual care group; mean [SD] age, 79.3 [8.4] years) included in the STEP-HI trial (122 (94.6%) provided primary outcome data for baseline and at least 1 time point (12 or 24 weeks). The mean (SD) change in the 6MWD between baseline and 24 weeks was not significantly different for exercise plus topical testosterone gel (n = 53; 42.7 [8.2] m) compared with exercise plus placebo gel (n = 51; 40.5 [8.4] m) and enhanced usual care (n = 18; 37.7 [14.8] m). In the STEP-HI randomized clinical trial, supervised exercise training combined with testosterone therapy conducted in older women recovering from a hip fracture did not lead to significant improvement in 6MWD compared with supervised exercise alone. Adding testosterone therapy to exercise may not provide further benefits for long-distance mobility. Whether it can improve physical performance and mobility for short distances in this patient population warrants further study. ClinicalTrials.gov Identifier: NCT02938923

The Risk Reduction for Alzheimer's Disease (rrAD) trial included 513 cognitively normal, sedentary, hypertensive older adults (aged 60 to 85 years) with dementia risk factors. We utilized 420 high-quality baseline resting-state functional MRI (rs-fMRI) scans from this cohort to develop a functional atlas tailored for aging populations. Typical rs-fMRI atlases derived from healthy young adults do not account for age-related changes, such as cortical atrophy, enlarged ventricles, and altered connectivity. To address this gap, we created a cohort-specific MNI-adjacent anatomical template, rrAD420, using SPM12's DARTEL registration. In this space, we derived a comprehensive functional atlas using both group independent component analysis (GICA) and probabilistic functional mode decomposition (PROFUMO). The rrAD420 atlas offers detailed representations of Resting-State Network (RSN) connectivity, encompassing unique configurations and overlapping interactions. It features two Default-Mode Network (DMN)-specific seed-based maps (DMN24 with cerebellum, DMN18 without) and data-driven components resembling the major RSNs. Furthermore, PROFUMO allowed for the identification of multimodal and combinatory networks, capturing connections within and between RSNs. While optimized for hypertensive older adults, the rrAD420 atlas serves as a versatile tool for broader aging populations, aiding in the study of neurodegenerative processes and biomarker discovery.

BACKGROUND:High psychological resilience is associated with improved functional outcomes for older adults recovering from hip fractures. The objective of this study was to identify factors associated with increased psychological resilience in older women after hip fracture. METHODS:In total, 129 women aged ≥65 years with recent surgically repaired hip fractures were enrolled in a trial of exercise and testosterone therapy. The Brief Resilience Scale (BRS) measured baseline resilience and was categorized as low (BRS < 4) or high (BRS ≥ 4). Sociodemographic (eg, education), medical, and neuropsychological factors (eg, cognition by Short Blessed Test, mental health by a Global Mental Health Score (PROMIS-GMH), and depressive symptoms by Geriatric Depression Score (GDS)) were considered as independent variables. Individual factors were evaluated for their association with resilience using bivariate regression, and those having a significance level of p ≤ .10 were entered into age-adjusted multivariate logistic regression models. RESULTS:A total of 57 women (44%) reported high resilience. Neither education nor cognition was significantly associated with resilience. Lower GDS and better PROMIS-GMH scores were associated with high resilience in adjusted models. For every one-point worsening in GDS, the adjusted odds ratio (AOR) for high versus low resilience was 0.76 (95% CI, 0.61,0.93). In a model with GDS, PROMIS-GMH, and age, positive mental health remained significantly associated with higher resilience (AOR 1.34, 95% CI, 1.14,1.58). CONCLUSIONS:In older women after hip fracture, fewer depressive symptoms and better mental health were associated with higher psychological resilience. Addressing overall mental health when recovering from a hip fracture could contribute to increasing psychological resilience thereby maximizing recovery potential.

The Exercise and Intensive Vascular Risk Reduction in Preventing Dementia (rrAD study) was a multicenter randomized, controlled trial to determine the effects of moderate to vigorous aerobic exercise training and intensive pharmacological treatment of cardiovascular risk factors on dementia prevention in older adults (NCT02913664). The trial duration was 2 years. We present herein the adverse events (AEs) reported in the rrAD trial. Our objective is to determine whether the trial interventions were associated with higher reports of AEs in older adults aged 60 to 85 who had hypertension, family history of dementia, and/or subjective memory complaints. 513 subjects were randomized to one of four intervention treatment arms: Aerobic Exercise (Ex), Intensive Reduction of Vascular Risk Factors (IRVR), Combined Arm (IRVR+Ex), and Usual Care. The IRVR groups received intensive pharmacological treatment of blood pressure (BP) (SBP<130mmHg) and cholesterol management (atorvastatin, 80mg daily). AEs were categorized by the abnormal lab results and body systems which are likely affected by the trial interventions. The IRVR arms had slightly higher abnormal lab results of electrolytes (potassium) and creatinine (Table 1) relative to the non-IRVR arms, which were expected with BP treatment using angiotensin receptor blockers (ARBs) such as, losartan. The IRVR arms also had higher AEs of leg cramps, edema, dizziness, lightheadedness, and fatigue likely reflecting side effects of antihypertensives and/or statin use. The exercise arms had higher AEs in the musculoskeletal system relative to the non-exercise arms. Overall, the rates of injuries, serious adverse events (SAEs), or death were low, and no noticeable differences were observed among the intervention arms. Participants in the IRVR arms may report higher AEs related to the side effects of antihypertensives and/or statin use, and in the exercise arms higher AEs related to musculoskeletal events such as muscle pain. The rrAD study showed that it is safe to implement moderate to vigorous aerobic exercise training and intensive cardiovascular risk factor reduction in older adults for dementia prevention.

Abstract Hip fractures are common among older women and can have a devastating impact on their ability to remain independent. Many women who were high functioning before the hip fracture do not return to their pre-fracture level of function, have persistent weakness and mobility impairments, and may require ongoing supportive services. Age-associated androgen deficiency may contribute to deficits in muscle mass, strength and power that are common in older female hip fracture patients. The typical approach to hip fracture rehabilitation routinely includes a limited course of physical therapy but the precise role of exercise and the use of an anabolic therapy like testosterone has not been determined. The Starting a Testosterone and Exercise Program after Hip Injury (STEP-HI) Study is a three-group, randomized, double-blinded, placebo-controlled Phase III clinical trial that was conducted at 8 clinical sites in the USA. The trial was designed to evaluate a multi-modal intervention aimed at improving functional outcomes in older female hip fracture patients with persistent mobility impairment. 129 female hip fracture patients, age 65 yrs. and older were randomly assigned to one of three groups: supervised exercise plus 1% testosterone topical gel (EX+T); supervised exercise plus placebo gel (EX+P); or Enhanced Usual Care (EUC). This symposium will present the results of the trial, including recruitment and retention, primary and secondary outcome measures. The program will also address strategies to ensure fidelity with exercise in a multicenter study like STEP-HI. Implications of study findings for future research and clinical practice will be discussed.

Abstract The STEP-HI Study tested if testosterone replacement therapy in combination with resistance exercise training for 6 months could improve functional recovery from hip fracture in older women more than resistance exercise alone or standard of care. Here we present the results of the intention to treat analyses (N=122) of the effect of testosterone replacement plus exercise (EX+T, n=53) vs. exercise plus placebo (EX+P, n=51) vs. enhanced usual care (EUC, n=18) on the Short Physical Performance Battery (SPPB) scores, maximal leg press strength, and appendicular lean mass. Group differences were analyzed with contrasts using a mixed model repeated analysis of variance that included the following covariates for each outcome: clinical site, age, days since hip surgery, BMI, hip fracture type, general depression score, lung disease, comorbidity index and baseline level. EX+T had a greater improvement in SPPB score than EX+P (p<0.009). Maximal leg press strength increased in all groups by the end of the intervention period with no differences between groups (p>0.05). Appendicular lean mass increased to the same extent in the EX+T and EX+P groups, but slightly decreased in the EUC group as compared to EX+T (p=0.020) and EX+P (p=0.029). These findings suggest that testosterone may independently impact a composite measure of physical performance, while exercise significantly improves appendicular lean mass independent of testosterone replacement. The implications of these findings will be discussed.

Abstract For STEP-HI women aged ≥65 years with a recent hip fracture were recruited from the community at large and Assisted Living facilities. Women who qualified for the study were assigned to one of three groups for 6 months: exercise plus testosterone (EX+T), exercise plus placebo (EX+P), or Enhanced Usual Care (EUC). EX+T were prescribed a dose of 1% testosterone topical gel intended to maintain serum total testosterone levels between 110-160 ng/dL. Both EX groups performed a supervised exercise program; EUC participants performed home exercise. To identify eligible patients 4695 chart reviews were completed, 207 women consented for screening, 153 were eligible, 129 were randomized to study groups, 122 included in the intention-to-treat (ITT) analyses. Mean age of the sample was 79.3 ± 8.4. Women assigned to the EX+T group achieved a mean serum total testosterone level of 170.1 ± 82.7 ng/dL, compared with 17.8 ± 13.3 ng/dL in the EX+P group (p< 0.001). Adherence to the supervised exercise program (number completed/number of expected sessions) was 82.5% in the EX+T group and 81.1% in the EX+P group (p = 0.68). The pre-specified primary outcome measure was Six Minute Walk Distance (SMWD). In the ITT analysis, SMWD increased over the 6-month intervention period in all three groups, but the changes in EX+T (n=53) vs. EX+P (n=51) vs. EUC (n=18) did not differ significantly by group (p> 0.39 for all comparisons). We conclude that in older women with a recent hip fracture, testosterone replacement therapy does not independently improve SMWD greater than exercise.

Importance Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. Objective The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. Design The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. Results 107 participants (mean age: 54 +/- 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. Conclusion and relevance The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

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.

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.

Background Community-dwelling older adults experiencing hip fracture often fail to achieve adequate walking capacity following surgery and rehabilitation. Effects of psychological factors on post-fracture walking capacity are poorly understood. Accordingly, this paper investigates effects of psychological resilience on observed walking capacity measures in older adults following hip fracture, controlling for important covariates. Methods Data were drawn from the Community Ambulation Project, a clinical trial of 210 community-dwelling adults aged >= 60 years who experienced a minimal trauma hip fracture and were randomized to one of two 16-week home-based physical therapist-guided interventions. Psychological resilience was measured at study baseline using the 6-item Brief Resilience Scale (BRS); scores were classified into groups in order to distinguish levels of self-reported resilience. Walking capacity was assessed at study baseline and 16 weeks later using 4-Meter Gait Speed (4MGS), 50-Foot Walk Test (50FWT), and 6-Minute Walk Distance (SMWD). In multivariate analyses of covariance in which 16-week follow-up values of each walking measure were outcomes, covariates included clinical trial arm, gender, age, and baseline values of: walking measure corresponding to the outcome; body mass index; depressive symptom severity; degree of psychological optimism; cognitive status; informal caregiver need; and days from hospital admission to randomization. Results Increases between baseline and 16 weeks later in mean gait speed in meters/sec (m/s) and walking distance in meters (m) in 4MGS, 50FWT and SMWD were 0.06 m/s (p = 0.061), 0.11 m/s (p < 0.01), and 25.5 m (p = 0.056) greater, respectively, in the most resilient BRS group compared to the least resilient BRS group. Conclusion Higher levels of psychological resilience were associated with greater walking speed and distance. Psychological resilience represents a potentially clinically important pathway and intervention target, toward the goal of improving walking capacity among older adults known to have substantial residual disability following hip fracture.

Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization.

Risk Reduction for Alzheimer’s Disease (rrAD) is a recently completed randomized controlled trial assessing the effects of aerobic exercise training and pharmacological cardio-vascular interventions on neurocognitive function in hypertensive older adults with a family history of dementia or subjective cognitive decline. The comprehensive neuroimaging protocol included anatomical, functional, and physiological MRI scans, obtained at baseline and after two years of intervention. 420 older subjects (68.8±5.9 years) were scanned on five different 3T MRI scanners (two Siemens, two GE, and one Philips). Brain atrophy and ventricular enlargement are common in this elderly study population, leading to substantial deviations from the standard MNI152 template (25.02±4.9 years). Severe artifacts might occur when transforming non-normative brains into MNI standard space. Using the high-quality baseline data of this study, we aim to integrate images from multiple modalities to create a reference that is better suited to investigate older populations. For each subject, we acquired T1 MPRAGE, T2 FLAIR, ASL, DTI, and resting-state fMRI. Each scan underwent rigorous manual quality control and linear sequence-specific high precision alignment to the T1 image. All T1 images then underwent non-linear DARTEL registration into a common space to create cohort-specific transformations. We then transformed all images into the new common space, namely rrAD420 ( Figure 1 ). Averages across subjects make up cohort- and modality-specific templates ( Figure 2 ). Seed-based and data-driven decompositions of resting-state fMRI and DTI data created functional and structural connectivity atlases ( Figure 3 ). Anatomical dual regression transforms common brain atlases from MNI into rrAD420 space, facilitating cross-referencing. The rrAD420 templates and atlases integrate multimodal neuroimaging data of older populations into a common space, accounting for cohort-specific distinctions, such as cortical atrophy and enlarged ventricles. It provides references to commonly used brain parcellations which are integrated with functional and structural atlases created from the rrAD cohort. Thus, rrAD420 provides a reference framework for comprehensive multimodal MRI analyses of elderly cohorts. Through rrAD420, longitudinal multi-modal image analyses can now be carried out using templates unique to this population. Furthermore, rrAD420 should also apply to older populations in general, facilitating data integration, and biomarker detection.