A Nutritional Formulation for Cognitive Performance and Mood in Alzheimer’s Disease and Mild Cognitive Impairment: A Phase II Multi-site Randomized Trial with an Open-label Extension

Background: It is increasingly recognized that interventions for dementia must shift towards prevention to obtain maximal efficacy and any significant degree of disease modification. Nutritional supplementation with single agents has shown varied results, suggesting the need for combinatorial intervention. Methods: We conducted a 3-month, randomized, multi-site, phase II study in which 141 individuals diagnosed with Alzheimer’s disease (AD) and 34 individuals with Mild Cognitive Impairment received a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo under double-blind conditions, followed by an open-label extension in which all individuals received NF for a total of 1yr. An additional 38 individuals with AD received NF under open-label conditions from baseline for 1yr. The primary outcome was defined as cognitive performance. Secondary outcomes were defined as behavioral and psychological symptoms of dementia and activities of daily living. Results: Participants randomized to NF improved statistically within 3 months in cognitive performance as ascertained by Clox-1 and the Dementia Rating Scale, and their caregivers reported improvement in Neuropsychiatric Inventory. Participants receiving NF either continued to improve or maintained their baseline performance during open-label extensions. Participants randomized to placebo did not improve, but during open-label extensions displayed similar improvement within 3 months to that of participants initially randomized to NF. Caregivers reported no change in Activities of Daily Living for either cohort. Conclusions: These findings confirm and extend prior phase I studies in which NF improved or maintained cognitive performance and behavioral symptoms for individuals with AD, and improved cognitive performance for community-dwelling individuals without dementia. In published studies with transgenic mice NF reduced PS-1 expression, beta and gamma secretase activity, Abeta deposits, phospho-tau, homocysteine and oxidative damage, and increased acetylcholine and glutathione. This comprehensive impact of NF on AD-related neuropathology supports the possibility that NF may harbor disease-modifying properties

Myosteatosis as a Shared Biomarker for Sarcopenia and Cachexia Using MRI and Ultrasound

PurposeEstablish bedside biomarkers of myosteatosis for sarcopenia and cachexia. We compared ultrasound biomarkers against MRI-based percent fat, histology, and CT-based muscle density among healthy adults and adults undergoing treatment for lung cancer.MethodsWe compared ultrasound and MRI myosteatosis measures among young healthy, older healthy, and older adults with non-small cell lung cancer undergoing systemic treatment, all without significant medical concerns, in a cross-sectional pilot study. We assessed each participant's rectus femoris ultrasound-based echo intensity (EI), shear wave elastography-based shear wave speed, and MRI-based proton density fat-fraction (PDFF). We also assessed BMI, rectus femoris thickness and cross-sectional area. Rectus femoris biopsies were taken for all older adults (n = 20) and we analyzed chest CT scans for older adults undergoing treatment (n = 10). We determined associations between muscle assessments and BMI, and compared these assessments between groups.ResultsA total of 10 young healthy adults, 10 older healthy adults, and 10 older adults undergoing treatment were recruited. PDFF was lower in young adults than in older healthy adults and older adults undergoing treatment (0.3 vs. 2.8 vs. 2.9%, respectively, p = 0.01). Young adults had significantly lower EI than older healthy adults, but not older adults undergoing treatment (48.6 vs. 81.8 vs. 75.4, p = 0.02). When comparing associations between measures, PDFF was strongly associated with EI (ρ = 0.75, p < 0.01) and moderately negatively associated with shear wave speed (ρ = −0.49, p < 0.01) but not BMI, whole leg cross-sectional area, or rectus femoris cross-sectional area. Among participants with CT scans, paraspinal muscle density was significantly associated with PDFF (ρ = −0.70, p = 0.023). Histological markers of inflammation or degradation did not differ between older adult groups.ConclusionPDFF was sensitive to myosteatosis between young adults and both older adult groups. EI was less sensitive to myosteatosis between groups, yet EI was strongly associated with PDFF unlike BMI, which is typically used in cachexia diagnosis. Our results suggest that ultrasound measures may serve to determine myosteatosis at the bedside and are more useful diagnostically than traditional weight assessments like BMI. These results show promise of using EI, shear wave speed, and PDFF proxies of myosteatosis as diagnostic and therapeutic biomarkers of sarcopenia and cachexia

The effect of computed tomography parameters on sarcopenia and myosteatosis assessment: a scoping review

Abstract Computed tomography (CT) is a valuable assessment method for muscle pathologies such as sarcopenia, cachexia, and myosteatosis. However, several key underappreciated scan imaging parameters need consideration for both research and clinical use, specifically CT kilovoltage and the use of contrast material. We conducted a scoping review to assess these effects on CT muscle measures. We reviewed articles from PubMed, Scopus, and Web of Science from 1970 to 2020 on the effect of intravenous contrast material and variation in CT kilovoltage on muscle mass and density. We identified 971 articles on contrast and 277 articles on kilovoltage. The number of articles that met inclusion criteria for contrast and kilovoltage was 11 and 7, respectively. Ten studies evaluated the effect of contrast on muscle density of which nine found that contrast significantly increases CT muscle density (arterial phase 6–23% increase, venous phase 19–57% increase, and delayed phase 23–43% increase). Seven out of 10 studies evaluating the effect of contrast on muscle area found significant increases in area due to contrast (≤2.58%). Six studies evaluating kilovoltage on muscle density found that lower kilovoltage resulted in a higher muscle density (14–40% increase). One study reported a significant decrease in muscle area when reducing kilovoltage (2.9%). The use of contrast and kilovoltage variations can have dramatic effects on skeletal muscle analysis and should be considered and reported in CT muscle analysis research. These significant factors in CT skeletal muscle analysis can alter clinical and research outcomes and are therefore a barrier to clinical application unless better appreciated

Computed tomography measured tissue density of pectoral muscle and liver predicts outcomes in heart transplant recipients

Abstract Background Computed tomography (CT)‐derived measures of tissue quality can add to frailty assessment and improve selection of candidates for heart transplant. We investigated the prognostic value of CT measures of tissue density for predicting hospital length of stay (LOS) and mortality post‐transplant. Methods All patients at a quaternary care hospital between 1999 to 2018 with preheart transplant CT scans and available data on transplant outcomes were eligible (n = 189), including a subset within the total cohort with scans 6‐month pretransplant (n = 103). Axial chest CT scans were analysed for liver and muscle density at the 12th thoracic vertebrae and aortic arch landmarks, respectively. Cox and linear regression models examined the risk of death and LOS, respectively, according to median (above or below) pectoral muscle density. Low‐density muscle (LDM) area and liver density were analysed as continuous variables. Results Out of 157 patients with readable CT scans (median age 55 years, interquartile range [50–60] 10% women), 31 died on 1‐year follow up. Patients with higher than and at median pectoral muscle density (39.5 Hounsfield Unit [HU]) had better 1‐year survival in the overall cohort (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.673, 0.989; p = 0.039), with the 6‐month cohort showing a trend (HR 0.79, 95% CI 0.603, 1.023; p = 0.074) towards improved survival. Conversely, every 5‐cm2 increase in pectoral LDM area was associated with 2.4‐day lower LOS (p = 0.045) in the overall cohort, and a 2.6‐day lower LOS in the 6‐month cohort (p = 0.05). Patients with higher ratio of normal‐density muscle to LDM had higher LOS (p < 0.01). Every 5‐HU increase in liver density at a region of interest was associated with 0.24‐day higher post‐transplant LOS in the overall cohort, and a 0.41 higher LOS in the 6‐month cohort (p ≤ 0.05). Conclusions Patients with higher preheart transplant pectoral muscle density had greater 1‐year survival. Higher pectoral LDM area was associated with decreased LOS post‐transplant and higher liver density was associated with increased LOS. These findings raise possibilities that measures of muscle density as they reflect to quality of muscle may have prognostic implications. Future studies with prospective design are needed to confirm these findings