The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population

Alzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.

Designing, Conducting, and Documenting Human Nutrition Plant-Derived Intervention Trials

Best practices for designing, conducting, documenting, and reporting human nutrition randomized controlled trials were developed and published in Advances in Nutrition. Through an example of the randomized clinical trial on blueberries and bone health funded by the National Institutes of Health, this paper will illustrate the elements of those best practices that apply specifically to plant-based intervention clinical trials. Unique study design considerations for human feeding interventions with bioactive plant compounds include the difficulty of blinding the intervention, background nutritional status of participants, carry-over effects of the intervention, benefits of a run-in period, lack of safety/tolerability data, and nutrition-specific regulatory policies. Human nutrition randomized controlled trials are the gold standard for establishing causal relations between an intervention and health outcome measures. Rigorous studies and documentation define the quality of the evidence-base to inform public health guidelines and to establish personalized dietary recommendations for the health-promoting plant components.

Interventions That Successfully Reduced Adults Salt Intake—A Systematic Review

Background: Adequate sodium intake is important for lowering blood pressure and thus reducing cardiovascular disease risk and other complications. The aim of this review is to identify recent interventions around the world that have been successful in reducing salt intake. Methods: A search in the PubMed, Web of Science and Scopus databases was performed. We include studies published in the last 10 years; randomized trials, pilot intervention without a control arm or experimental study; adult participants; and interventions that successfully reduced salt intake. Study quality was assessed. Results: We included 21 studies, 16 randomized intervention trials and five nonrandomized intervention studies. Eleven interventions described health and nutritional education, seven interventions described nutritional education plus other interventions, and three studies used salt meters to reduce sodium intake. Conclusion: Health and nutritional education, nutritional education plus other interventions and estimates of salt intake showed success in the reduction of salt consumption. There is no evidence that one type of intervention analyzed is more effective than other in reducing salt consumption, so we must analyze each in which individuals or subpopulations will have the intervention performed and use the most suitable approaches to lead to better results.

Maintaining Integrity of Worldwide FINGER Clinical Trials During the COVID-19 Pandemic

The COVID-19 pandemic presents challenges to the conduct of randomized clinical trials of lifestyle interventions. World-Wide FINGERS international network convened a forum for researchers to discuss statistical design and analysis issues they faced during the pandemic. We report experiences of three trials that, at various stages of conduct, altered designs and analysis plans to navigate these issues. We provide recommendations for future trials to consider as they develop and launch behavioral intervention trials. The pandemic led researchers to change recruitment plans, interrupt timelines for assessments and intervention delivery, and move to remote intervention and assessments protocols. The necessity of these changes add emphasis to the importance, in study design and analysis, of intention to treat approaches, flexibility, within site stratification, interim power projections, and sensitivity analyses. Robust approaches to study design and analysis are critical to negotiate issues related to the intervention.

Community Engagement and Human-Centered Design: Lessons From HEARS in Inclusive Recruitment of Older Adults

Within hearing care, significant disparities persist despite the highly prevalent nature of age-related hearing loss and relatively few trials include representation of racial/ethnic minorities. HEARS is an affordable, accessible hearing care intervention delivered by older adult peer mentors. The HEARS randomized controlled trial (NCT03442296) is a community-engaged RCT with an embedded human-centered design practitioner. Recruitment efforts occurred over 18 months in partnership with 13 affordable housing and social centers. The cohort (n=151) includes 43% (n=65) who self-identify as African American and 63.6% (n=96) with <$25,000 annual household income. The cohort represents the largest to-date of African American and low-income older adults with hearing loss. Recruitment efforts entailed 470.5 staff hours and $4,917.26 in supplies, equating to 1.4 hours and $14.13 per 1 individual screened and 3.1 hours and $32.56 for 1 participant randomized. Community-engaged research, partnered with human-centered design, may offer critical approaches to increasing representation within behavioral intervention trials.

Recruitment Challenges and Strategies for Multimodal Intervention Trials

Determining ways to improve hip fracture recovery in older adults is important, however recruitment of this target population into clinical trials is challenging. Multimodal interventions that target multiple mechanisms of recovery may improve outcomes, but each component presents unique recruitment barriers. While exercise interventions have been shown to be beneficial for hip fracture recovery, offering exercise following completion of conventional physical therapy can be viewed as a burdensome time commitment. Hormone replacement therapy may hold promise for overcoming anabolic resistance, but concern about adverse side effects can also deter participation. STEP-HI is a multisite trial testing whether exercise and testosterone can improve hip fracture recovery in older women. In this talk, recruitment barriers experienced in STEP-HI and strategies employed to overcome these barriers will be discussed. Strategies include: partnering with hospitals, skilled nursing facilities and orthopedic surgeons. providing talks and education materials; and featuring past participant testimonials in recruitment materials.

Sex-Specific 25-Hydroxyvitamin D Threshold Concentrations for Functional Outcomes in Older Adults

25-Hydroxyvitamin D [25(OH)D] has extra-skeletal effects, but it is not known whether the minimum sufficient serum levels for such targets, like muscle, differ from those for bone health (typically recommended at 20 or 30 ng/dL). Therefore, we derived and validated sex-specific thresholds for serum 25(OH)D predictive of poor physical function using 5 cohorts comprising 16,388 community-dwelling older adults (60.9% women). Using a cohort-stratified random two-thirds sample, we found incident slow gait was best discriminated by 25(OH)D<24.0 versus 25(OH)D>=24.0 ng/mL among women (Relative Risk=1.29; 95% CI 1.10-1.50) and 25(OH)D<21.0 versus 25(OH)D >=21.0 ng/mL among men (RR=1.43; 95% CI 1.01-2.02). Estimates from the remaining one-third validation sample were similar. Empirically identified and validated sex-specific 25(OH)D thresholds from multiple well-characterized cohorts of older adults may yield more biologically meaningful definitions in important sub-populations. Such thresholds may serve as candidate reference concentrations or inform design of vitamin D intervention trials in older adults.

The Effects of Fruit-Derived Polyphenols on Cognition and Lung Function in Healthy Adults: A Systematic Review and Meta-Analysis

Polyphenols are plant derived nutrients that influence oxidative stress and inflammation and therefore may have positive benefits on cognition and lung function. This systematic review and meta-analysis aimed to evaluate the effects of fruit derived polyphenol intakes on cognition and lung capacity in healthy adults. In August 2020 and October 2021, Medline and Google Scholar were used to search for relevant studies examining the effects of fruit derived polyphenol intakes on cognition and/or lung function in healthy adults (<70 years old). Fourteen studies related to cognition (409 healthy subjects) and seven lung/respiratory studies (20 788 subjects) were used for the systematic review using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The meta-analysis (using six cognition and three lung function studies) indicated a protective effect on lung function from dietary intakes of fruit-derived polyphenols. Neither a benefit nor decrement from fruit-derived polyphenol intakes were detected for cognition. Human intervention trials examining the effects of polyphenol supplementation on lung function in healthy adults are scarce and intervention studies are warranted. More conclusive results are needed to provide recommendations for polyphenol supplementation to support aspects of cognition.