Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein-energy malnutrition in predementia aged people: study protocol for Choko-Age.

OBJECTIVE: Protein-energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly. METHODS AND ANALYSIS: In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the 'Joint Programming Initiative A healthy diet for a healthy life'. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9-1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics. ETHICS AND DISSEMINATION: All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects' regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals. TRIAL REGISTRATION NUMBER: NCT05343611.

Exercise training improves vascular function in patients with Alzheimer's disease.

PURPOSE: Vascular dysfunction has been demonstrated in patients with Alzheimer's disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD. METHODS: Thirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate-high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session. RESULTS: EX group has increased FMD% (+ 3.725%, p < 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p < 0.05; SR + 134%, p < 0.05), but not during CTRL treatment. CONCLUSION: Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population.

Non-Aß-Dependent Factors Associated with Global Cognitive and Physical Function in Alzheimer's Disease: A Pilot Multivariate Analysis.

Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aß-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO2max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA). Baseline multifactorial information was submitted to two separate backward stepwise regression analyses to identify the variables associated with cognitive and physical decline in demented patients. A multivariate regression was then applied to verify the stepwise regression. The results indicated that the combination of 6MWT and VO2max was associated with both global cognitive and physical function (MMSE = 11.384 + (0.00599 × 6MWT) - (0.235 × VO2max)); (PPT = 1.848 + (0.0264 × 6MWT) + (19.693 × VO2max)). These results may offer important information that might help to identify specific targets for therapeutic strategies (NIH Clinical trial identification number NCT03034746).

Age-Associated ALU Element Instability in White Blood Cells Is Linked to Lower Survival in Elderly Adults: A Preliminary Cohort Study.

BACKGROUND: ALU element instability could contribute to gene function variance in aging, and may partly explain variation in human lifespan. OBJECTIVE: To assess the role of ALU element instability in human aging and the potential efficacy of ALU element content as a marker of biological aging and survival. DESIGN: Preliminary cohort study. METHODS: We measured two high frequency ALU element subfamilies, ALU-J and ALU-Sx, by a single qPCR assay and compared ALU-J/Sx content in white blood cell (WBCs) and skeletal muscle cell (SMCs) biopsies from twenty-three elderly adults with sixteen healthy sex-balanced young adults; all-cause survival rates of elderly adults predicted by ALU-J/Sx content in both tissues; and cardiovascular disease (CVD)- and cancer-specific survival rates of elderly adults predicted by ALU-J/Sx content in both tissues, as planned subgroup analyses. RESULTS: We found greater ALU-J/Sx content variance in WBCs from elderly adults than young adults (P < 0.001) with no difference in SMCs (P = 0.94). Elderly adults with low WBC ALU-J/Sx content had worse four-year all-cause and CVD-associated survival than those with high ALU-J/Sx content (both P = 0.03 and hazard ratios (HR) ≥ 3.40), while WBC ALU-J/Sx content had no influence on cancer-associated survival (P = 0.42 and HR = 0.74). SMC ALU-J/Sx content had no influence on all-cause, CVD- or cancer -associated survival (all P ≥ 0.26; HR ≤ 2.07). CONCLUSIONS: These initial findings demonstrate that ALU element instability occurs with advanced age in WBCs, but not SMCs, and imparts greater risk of all-cause mortality that is likely driven by an increased risk for CVD and not cancer.