Data sharing as the foundation of discovery: ADNI and breakthroughs in Alzheimer's disease.

The COVID pandemic has shown that when the research community comes together, we can conquer the most complex biomedical challenges. Collaboration and teamwork among federal agencies, private organizations, and researchers have been crucial in the development of vaccines and therapeutics against COVID. Possibly the first example of such cross-functional collaboration is the Alzheimer's Disease Neuroimaging Initiative (ADNI), the largest and longest continually monitored Alzheimer's study. ADNI was designed and operated as a public-private partnership, managed by the Foundation for the National Institutes of Health. This article shows how recent successes in the Alzheimer's field are directly a result of ADNI's open and transparent sharing of knowledge, expertise, and resources, which have allowed researchers to advance their understanding of Alzheimer's and tackle challenges in a relatively short period of time. ADNI's approach to open-source innovation also served as a model for addressing other complex diseases and led to numerous collaborative research initiatives. HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was designed, structured, and operated as a public-private partnership, managed by the Foundation for the National Institutes of Health. The recent successes in the Alzheimer's field are directly a result of ADNI's efforts. Open and transparent sharing of knowledge, expertise, and resources allowed researchers to advance their understanding of Alzheimer's and tackle challenges in a relatively short period of time.

Longitudinal association of infrapatellar fat pad signal intensity alteration with biochemical biomarkers in knee osteoarthritis.

OBJECTIVE: To explore the longitudinal association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with OA-related biomarkers. METHODS: Eighteen OA-related biochemical biomarkers of 600 knee OA participants in the Foundation for the National Institutes of Health OA Biomarkers Consortium (FNIH) study were extracted. The quantitative IPFP signal intensity measures were acquired based on magnetic resonance imaging, including mean value [Mean (IPFP)] and standard deviation [sDev (IPFP)] of the whole IPFP signal intensity, median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity, the ratio of volume of high signal intensity to volume of whole IPFP signal intensity [Percentage (H)] and Clustering factor (H). The linear mixed-effect model was applied to determine the longitudinal associations between IPFP signal intensity alteration and biochemical biomarkers over 2 years. RESULTS: All IPFP measures except for Clustering factor (H) were positively associated with urine collagenase-cleaved type II collagen neoepitope (uC2C), urine C-terminal cross-linked telopeptide of type II collagen (uCTX-II), urine C-terminal cross-linked telopeptide of type I collagen-α (uCTX-Iα) and urine N-terminal cross-linked telopeptide of type I collagen (uNTX-I). Mean (IPFP), Median (H) and Percentage (H) were positively associated with the nitrated form of an epitope located in the triple helix of type II collagen (Coll2-1 NO2). Mean (IPFP), Median (H) and UQ (H) were positively associated with sCTX-I and uCTX-Iß. Positive associations between sDev (IPFP), Percentage (H) and serum hyaluronic acid (sHA) were found. CONCLUSION: Our results suggest a role of IPFP signal intensity alteration in joint tissue remodelling on a molecular level.

Sarcopenia prevalence and associations with mortality and hospitalisation by various sarcopenia definitions in 85-89 year old community-dwelling men: a report from the ULSAM study.

BACKGROUND: Operational definitions of sarcopenia, i.e. loss of muscle function and mass, have been proposed by the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). The aim of this study was to analyse the prevalence and outcome, i.e. all-cause mortality and hospitalisation, of sarcopenia and its diagnostic components in octogenarian community-dwelling men. METHODS: In total 287 men, aged 85-89 y, participating in the Uppsala Longitudinal Study of Adult Men (ULSAM) underwent Dual X-ray Absorptiometry (DXA), measurement of hand grip strength (HGS), gait speed (GS), and a five-times chair stand test (CS). Sarcopenia and probable sarcopenia were defined according to EWGSOP (2010), EWGSOP2 (2018), and FNIH (2014). All-cause mortality and hospitalisations over 3 years were registered. RESULTS: Sarcopenia according to EWGSOP, EWGSOP2 and FNIH was observed in 21%, 20%, and 8% of the men, respectively, while probable sarcopenia (EWGSOP2; eq. reduced muscle strength only) was seen in 73%. "Sarcopenia (EWGSOP)" and "probable sarcopenia (EWGSOP2)" were associated with increased mortality (HR 1.95, 95% CI 1.12-3.40 and HR 3.26, 95% CI 1.38-7.70, respectively). "Probable sarcopenia (EWGSOP2)" was associated with days of hospitalisation (RR 2.12, 95% CI 1.36-3.30), whereas sarcopenia according to FNIH showed an association with the number of hospitalisations (RR 1.75, 95% CI 1.10-2.81). CONCLUSIONS: In very old men, reduced muscle strength, i.e. probable sarcopenia, was common and associated with mortality and length of stay during hospitalisation. When combined with low muscle mass (according to DXA), i.e. sarcopenia, the various definitions were associated more weakly with the adverse outcomes. The findings support the emphasis on reduced muscle strength as the major determinant of sarcopenia.

Validation of the FNIH sarcopenia criteria and SOF frailty index as predictors of long-term mortality in ambulatory older men.

OBJECTIVE: we aimed to evaluate the Foundation for the National Institutes of Health (FNIH) criteria for weakness and low muscle mass and the Study of Osteoporotic Fractures (SOF) frailty index for prediction of long-term, all-cause mortality. DESIGN: community-based cohort study. SETTING: semi-rural community of Merelbeke (Belgium). SUBJECTS: ambulatory men aged 74 and more (n = 191). METHODS: weakness was defined on previously established criteria as low grip strength (<26 kg) or low grip strength-to-body mass index (BMI) ratio (<1.00). Low muscle mass (dual-energy x-ray absorptiometry) was categorised as low appendicular lean mass (ALM; predefined <19.75 kg) or low ALM-to-BMI ratio (predefined <0.789). Frailty status was assessed using the components of weight loss, inability to rise from a chair and poor energy (SOF index). Survival time was calculated as the number of months from assessment in 2000 until death or up to 15 years of follow-up. RESULTS: mean age of the participants was 78.4 ± 3.5 years. Combined weakness and low muscle mass was present in 3-8% of men, depending on the criteria applied. Pre-frailty and frailty were present in 30 and 7% of men, respectively. After 15 years of follow-up, 165 men (86%) died. Both the presence of combined weakness and low ALM-to-BMI ratio (age-adjusted HR = 2.50, 95% CI = 1.30-4.79) and the presence of SOF frailty (age-adjusted HR = 2.64, 95% CI = 1.44-4.86) were associated with mortality. CONCLUSIONS: our findings confirm the predictive value for mortality of the non-distribution-based FNIH criteria and SOF index in older community-dwelling Belgian men.

Perspective: The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partner Scientific Board (PPSB).

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partner Scientific Board (PPSB) is comprised of representatives of private, for-profit entities (including pharmaceutical, biotechnology, diagnostics, imaging companies, and imaging contract research organizations), and nonprofit organizations that provide financial and scientific support to ADNI through the Foundation for the National Institutes of Health. The PPSB serves as an independent, open, and precompetitive forum in which all private sector and not-for-profit partners in ADNI can collaborate, share information, and offer scientific and private-sector perspectives and expertise on issues relating to the ADNI project. In this article, we review and highlight the role, activities, and contributions of the PPSB within the ADNI project, and provide a perspective on remaining unmet needs and future directions.

The impact of the Alzheimer's Disease Neuroimaging Initiative 2: What role do public-private partnerships have in pushing the boundaries of clinical and basic science research on Alzheimer's disease?

In the growing landscape of biomedical public-private-partnerships, particularly for Alzheimer's disease, the question is posed as to their value. What impacts do public-private-partnerships have on clinical and basic science research in Alzheimer's disease? The authors answer the question using the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a test case and example. ADNI is an exemplar of how public-private-partnerships can make an impact not only on clinical and basic science research and practice (including clinical trials), but also of how similar partnerships using ADNI as an example, can be designed to create a maximal impact within their fields.

Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions.

Cirrhosis predisposes to abnormalities in energy, hormonal, and immunological homeostasis. Disturbances in these metabolic processes create susceptibility to sarcopenia or pathological muscle wasting. Sarcopenia is prevalent in cirrhosis and its presence portends significant adverse outcomes including the length of hospital stay, infectious complications, and mortality. This highlights the importance of identification of at-risk individuals with early nutritional, therapeutic and physical therapy intervention. This manuscript summarizes literature relevant to sarcopenia in cirrhosis, describes current knowledge, and elucidates possible future directions.

Contribution of sarcopenia and physical inactivity to mortality in people with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Physical inactivity and sedentary lifestyle have contributed to the epidemic of obesity and non-alcoholic fatty liver disease (NAFLD). We assessed the association between physical activity, NAFLD, and sarcopenia, and their contributions to mortality. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 with Linked Mortality file (through 2015) was utilised. NAFLD was determined by the US Fatty Liver Index in the absence of secondary causes of liver disease. Sarcopenia was defined using appendicular lean mass divided by body mass index by the Foundation for the National Institutes of Health criteria. Activity level was determined using standard self-reports. Publicly available imputed dual-energy X-ray absorptiometry data sets were used. RESULTS: Of 4,611 NHANES participants (48.2% males; 72.5% White; mean age 45.9 years), NAFLD was present in 1,351 (29.3%), of whom 17.7% had sarcopenia. Of the NAFLD group, 46.3% was inactive, whilst intermediate and ideal physical activity rates were observed in 14.2% and 39.5%, respectively. Sarcopenia was significantly and inversely related to higher physical activity level, both amongst NAFLD (odds ratio [OR] = 0.45 [95% CI 0.30-0.69]) and non-NAFLD (OR = 0.51 [0.35-0.75]) groups. During a median follow-up of 13.5 years, a total of 586 subjects died, of whom 251 had NAFLD. Amongst those who died with NAFLD, 33.0% had sarcopenia and 54.3% were inactive. Compared with NAFLD without sarcopenia, NAFLD with sarcopenia was associated with a higher risk of all-cause (hazard ratio [HR] = 1.78 [1.16-2.73]), cardiac-specific (HR = 3.19 [1.17-8.74]), and cancer-specific mortality (HR = 2.12 [1.08-4.15]). CONCLUSIONS: Inactivity is associated with presence of sarcopenia, whilst sarcopenia is associated with increased mortality amongst NAFLD patients. Sarcopenia should be a part of clinical assessment of patients with NAFLD. Treatment of NAFLD should include optimal management of sarcopenia. LAY SUMMARY: Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have similar pathophysiological profiles. Our data show that sarcopenia is associated with inactivity in subjects with NAFLD. The presence of sarcopenia in patients with NAFLD poses increased risk for all-cause and cardiac-specific mortality.