Longitudinal Associations Between ATPase Inhibitory Factor 1, Growth Differentiation Factor-15, and Nutritional Status in Older Adults From the MAPT Study.

BACKGROUND: Weight and appetite regulation have been associated with the expression and secretion of ATPase inhibitory factor 1 (IF1) and growth differentiation factor-15 (GDF-15), 2 potential biomarkers for age-related mitochondrial dysfunction. The aim was to explore the associations between these biomarkers and nutritional variables in the Multidomain Alzheimer Preventive Trial study. METHODS: IF1 and GDF-15 plasma levels were quantified at 1-year follow-up. The nutritional status was measured using the Mini Nutritional Assessment (MNA) score variation between baseline and 1- and 2-year visits; appetite loss was extracted from the MNA. Bodyweight was measured every 6 months until the third year and then yearly until the fifth year of follow-up, and weight loss was established if the loss was greater than 5% or 10% within the past 6 or 12 months, respectively. Bidirectional associations of IF1 and GDF-15 levels with malnutrition, appetite, and weight loss were examined. The interactions between individual IF1 and GDF-15 with sex were explored. RESULTS: Four hundred and forty-eight participants had MNA data and 1 045 had weight loss data. All the associations between IF1 levels and the MNA score, appetite loss, and weight loss were nonsignificant. Higher GDF-15 levels were cross-sectionally associated with appetite loss at the first year of follow-up, and the GDF-15 highest quartile was associated with nearly 80% higher risks of weight loss over 4 years. Interactions between IF1 and GDF-15 levels, and between these 2 markers and sex were not significantly associated with the outcomes. CONCLUSIONS: GDF-15 plasma levels were related to key malnutrition criteria.

Current and investigational medications for the treatment of sarcopenia.

Sarcopenia, defined as the loss of muscle mass and function, is a widely prevalent and severe condition in older adults. Since 2016, it is recognized as a disease. Strength exercise training and nutritional support are the frontline treatment of sarcopenia, with no drug currently approved for this indication. However, new therapeutic options are emerging. In this review, we evidenced that only very few trials have focused on sarcopenia/sarcopenic patients. Most drug trials were performed in different clinical older populations (e.g., men with hypogonadism, post-menopausal women at risk for osteoporosis), and their efficacy were tested separately on the components of sarcopenia (muscle mass, muscle strength and physical performances). Results from trials testing the effects of Testosterone, Selective Androgen Receptor Modulators (SARMs), Estrogen, Dehydroepiandrosterone (DHEA), Insulin-like Growth Factor-1 (IGF-1), Growth Hormone (GH), GH Secretagogue (GHS), drug targeting Myostatin and Activin receptor pathway, Vitamin D, Angiotensin Converting Enzyme inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs), or ß-blockers, were compiled. Although some drugs have been effective in improving muscle mass and/or strength, this was not translated into clinically relevant improvements on physical performance. Finally, some promising molecules investigated in on-going clinical trials and in pre-clinical phase were summarized, including apelin and irisin.

Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 diabetes risk in humans: A prospective cohort study.

AIM: Mitochondrial dysfunction is associated with the development of type 2 diabetes mellitus (T2DM). It is thus of clinical relevance to identify plasma biomarkers of mitochondrial dysfunction associated with the risk of T2DM. ATPase inhibitory factor 1 (IF1) endogenously inhibits mitochondrial ATP synthase activity. Here, we analyzed association of the plasma IF1 level with markers of glucose homeostasis and with the conversion to new-onset diabetes (NOD) in individuals with prediabetes. METHODS: In the IT-DIAB prospective study, the baseline plasma level of IF1 was measured in 307 participants with prediabetes. The primary outcome was the incidence of NOD within five years of follow-up. Cross-sectional analysis of the IF1 level was also done in two independent interventional studies. Correlations between plasma IF1 and metabolic parameters at baseline were assessed by Spearman's correlation coefficients, and the association with the risk of NOD was determined using Cox proportional-hazards models. RESULTS: In IT-DIAB, the mean IF1 plasma level was lower in participants who developed NOD than in those who did not (537 ± 248 versus 621 ± 313 ng/mL, P   = 0.01). The plasma IF1 level negatively correlated with clinical variables associated with obesity and insulin resistance, including the body mass index (r = -0.20, P  = 0.0005) and homeostasis model assessment of insulin resistance (HOMA-IR). (r = -0.37, P < 0.0001). Conversely, IF1 was positively associated with plasma markers of cardiometabolic health, such as HDL-C (r = 0.63, P  <  0.0001) and apoA-I (r = 0.33, P  <  0.0001). These correlations were confirmed in cross-sectional analyses. In IT-DIAB, the IF1 level was significantly associated with a lower risk of T2DM after adjustment for age, sex, and fasting plasma glucose (HR [95% CI] per 1 SD = 0.76 [0.62; 0.94], P   = 0.012). CONCLUSION: We identified for the first time the mitochondrial-related biomarker IF1 as being associated with the risk of T2DM.

Effect of Long-Term Omega 3 Polyunsaturated Fatty Acid Supplementation with or without Multidomain Lifestyle Intervention on Muscle Strength in Older Adults: Secondary Analysis of the Multidomain Alzheimer Preventive Trial (MAPT).

BACKGROUND: The benefits of long-term omega 3 polyunsaturated fatty acid (ω3-PUFA) supplementation on muscle strength in older adults remains to be investigated. OBJECTIVES: We assessed the effect of ω3-PUFA supplementation and a multidomain (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on muscle strength. We also hypothesized that ω3-PUFA supplementation resulted in additional benefit in participants with a low docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) erythrocyte level at baseline and high adherence to the multidomain intervention sessions. DESIGN: We performed secondary analyses of the Multidomain Alzheimer Preventive Trial (MAPT), a 3-year, multicenter, randomized, placebo-controlled trial with four parallel groups. Participants were non-demented, aged 70 years or older. They were recruited in 13 memory clinics in France and Monaco between 30 May 2008 and 24 February 2011. Participants were randomly assigned to either ω3-PUFA alone (two capsules a day providing a total daily dose of 800 mg DHA and 225 mg EPA), ω3-PUFA plus the multidomain intervention (43 group sessions integrating advice for physical activity (PA), and nutrition, cognitive training, and three preventive consultations), the multidomain intervention plus placebo, or placebo alone. Our primary outcome was the change from baseline to 36 months of the muscle strength assessed with the repeated chair stand test and handgrip strength. RESULTS: A total of 1680 participants (75.34 years ± 4.42) were randomized. In the modified intention-to-treat population (n = 1679), no significant differences at 3-year follow-up were observed in the repeated chair stand test score between any of the three intervention groups and the placebo group. The between-group differences compared with placebo were -0.05388 (-0.6800 to 0.5723; Standard Error, SE = 0.3192; p = 0.8660) for the ω3-PUFA group, -0.3936 (-1.0217 to 0.2345; SE = 0.3180; p = 0.2192) for the multidomain intervention plus placebo group, and -0.6017 (-1.2255 to 0.02222; SE = 0.2092; p = 0.3202) for the combined intervention group. No significant effect was also found for the handgrip strength. Sensitivity analyses performed among participants with low (DHA+EPA) erythrocyte level at baseline (first quartile vs. others) or highly adherent participants (≥75% of the multidomain intervention sessions) revealed similar results. CONCLUSION: Low dose ω3-PUFA supplementation, either alone or in combination with a multidomain lifestyle intervention comprising physical activity counselling, had no significant effects on muscle strength over 3 years in elderly people.

Lack of cause-effect evidence for the association between exercise and mortality: a true scientific debate for a false clinical issue / Ausência de evidências científicas no tocante à associação de causa e efeito entre exercício físico e mortalidade: um debate científico verdadeiro, mas um falso problema clínico

A recent debate raises the issue that there is no cause-effect data from well-powered randomized controlled trials showing that exercise decreases mortality. In this opinion article, we further discuss this issue focusing on the definitions of physical activity (PA) and exercise and the clinical meaning-fulness of mortality in the context of PA and exercise. In sum, although mortality is a major clinical outcome, the extent to which its risk should guide PA global recommendations and even exercise prescription is probably negligible, in particular for the large majority of healthy individuals. The debate about prescribing exercise on the basis of cause-effect association regarding mortality is a scientific debate rather than a clinical decision discussion. Health professionals should continuing to stimulate sedentary people to increase their PA and to prescribe exercise adapted to the target population as both a preventive strategy and a therapeutic element, focusing in clinical outcomes individuals consider important

Um recente debate na literatura científica focalizou-se na ausência de evidências de uma associação de causa-e-efeito entre exercício físico (EF) e redução do risco de mortalidade. Neste ensaio teórico, essa questão é abordada com ênfase em dois aspectos: as definições de atividade física (AF) e EF e, a relevância clínica do desfecho mortalidade no contexto da prática de AF e de EF. Embora a mortalidade constitua um desfecho clínico de extrema importância, sua pertinência no tocante às recomendações de AF e à prescrição de EF é provavelmente ínfima, particularmente, com relação à grande maioria das pessoas que gozam de uma boa saúde. Dessa forma, este debate pertence mais a esfera científica do que à esfera das decisões clínicas. Os profissionais de saúde devem continuar aconselhando a prática de AF e orientando o EF voltado para a população-alvo tanto como estratégia preventiva quanto como elemento terapêutico.

Effects of multidomain lifestyle intervention, omega-3 supplementation or their combination on physical activity levels in older adults: secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) randomised controlled trial.

Background/objectives: to investigate the effects of a 3-year multidomain lifestyle intervention, omega-3 supplementation or both on physical activity (PA) in older adults with subjective memory complaints. Design/settings/subjects: the Multidomain Alzheimer Preventive Trial was a 3-year randomised controlled trial that enroled 1,680 community-dwelling adults aged 70 years or over, with subjective memory complaints. Participants were randomised to omega-3 supplementation (total daily dose of 800 mg docosahexanoic acid and up to 225 mg eicosapentanoic acid), multidomain intervention (nutritional and exercise counselling and cognitive training), omega-3 plus multidomain intervention or placebo with usual care. Methods: PA was assessed using a self-reported questionnaire. From this, global moderate-to-vigorous PA, leisure-time PA, non-leisure-time PA and light PA were measured in metabolic equivalent tasks-minutes per week (MET-min/week). Results: in the multidomain groups, participants significantly increased their moderate-to-vigorous and leisure-time PA at 6 months (≥300 MET-min/week for both in the multidomain groups; P ≤ 0.002) before returning to baseline by the end of the trial. Activity in the placebo/usual care and omega-3/usual care groups declined overtime. Between-group differences remained significant for both multidomain groups for leisure-time physical activity at 2- and 3-year follow-ups. Compared to placebo/usual care, interventions had no significant effects on non-leisure-time PA and light PA. Omega-3 supplementation alone had no effects on PA. Conclusions: a multidomain intervention focused on cognitive training, and nutritional and PA counselling increased PA in the short-term and limited its decline in the long-term among older adults with memory complaints. ClinicalTrials.gov-Registration number: NCT0067268.

Potentially inappropriate drug prescribing and associated factors in nursing homes.

IMPORTANCE: Polymedication is frequent in nursing home (NH) residents. This increases the risk of potentially inappropriate drug prescribing (PIDP), which can lead to adverse drug events, such as falls and hospitalization. OBJECTIVE: To identify PIDP in NH residents and to investigate subject-related and NH structural and organizational factors associated with PIDP. DESIGN: Cross-sectional study. SETTING: A total of 175 NHs in Midi-Pyrénées region, South-Western France. PARTICIPANTS: A total of 974 subjects randomly selected from the 6275 NH residents participating in the IQUARE study. EXPOSURE: Patients with PIDP. MAIN OUTCOMES AND MEASURES: PIDP was the main outcome measure. It was defined using a specific indicator, based on the Summary of Product Characteristics, on the Laroche list, and on residents' clinical data. PIDP was defined as the presence of at least 1 of the following criteria: (1) drug with an unfavorable benefit-to-risk ratio; (2) drug with questionable efficacy according to the Laroche list; (3) absolute contraindication; (4) significant drug-drug interaction. Associated factors were identified by using multivariable logistic regression models. RESULTS: Among the 974 residents included, 71% had PIDP. PIDP was more frequent in patients without dementia, with several comorbidities and taking multiple medications. In the multivariable analysis, age (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.01-1.03) and Charlson Comorbidity Index (CCI; P = .003, CCI = 1 versus 0: OR1/0 1.22; 95% CI 0.85-1.74, CCI ≥ 2 versus 0: OR2/0 1.72; 95% CI 1.23-2.41) were associated with an increased likelihood of PIDP. By contrast, dementia was associated with a lower likelihood of PIDP (OR 0.70; 95% CI 0.53-0.94). Among NH structural and organizational characteristics, the access to psychiatric advice and/or to hospitalization in a psychiatric unit (OR 1.36; 95% CI 1.02-1.82) and the presence of a reevaluation of drug prescriptions (OR 1.45; 95% CI 1.07-1.96) were associated with an increased likelihood of PIDP. CONCLUSIONS AND RELEVANCE: Our work suggests that some NH characteristics are associated with an increased likelihood of PIDP. Gaining a better understanding of the factors influencing PIDP, especially structural and organizational NH factors, can help to determine the interventions that should be implemented.

Alzheimer's disease: learning from the past, looking to the future.

Our understanding on the pathophysiology and clinical aspects related to Alzheimer's Disease (AD) have been largely improved since the first case recorded in the medical literature in the beginning of the 20(th) century. Regarding the age of onset of AD, an important change seems to have happened in the last century: from several AD cases reported in middle aged and young adults in the first half of the 20(th) century, the age of onset of AD seems to have increased at the end of that century and the beginning of the 21(st) century. Since the 1-century-long time interval is very narrow to make a hypothesis on a genetic modification, it is possible that modifiable risk factors of AD played a role in increasing the age of onset of AD. Although the exact etiology of AD remains unknown, experts currently agree that it is multifactorial, being the result of complex interactions among genetic, environmental and lifestyle factors, such as physical activity, nutrition, and smoking. In the present article, we briefly discuss how lifestyle trends in the last century may have contributed to the increase in the age of onset of AD, and propose future directions for research on AD and lifestyle factors.

Temporal comparison theory and elderly satisfaction with their body: a preliminary study / Teoria da comparação corporal e satisfação corporal de idosos: um estudo preliminar

OBJECTIVES: Studies on body satisfaction have been neglecting a possible contribution of temporal comparisons (TC) for determining people's satisfaction with their body. The purpose of this work is to provide preliminary data on the usefulness of TC theory in determining body satisfaction in elderly individuals. METHODS: Participants were 18 functionally limited elderly adults, aged 68-90 years. After receiving three theory-related stimuli (social comparison, temporal comparison, and self-schema), they completed two scales: a scale on satisfaction with body functioning and a scale on body appearance satisfaction. RESULTS: Satisfaction with body functioning and satisfaction with body appearance did not differ among theory-related stimuli. TC-related correlations were stronger than the other theory-related correlations, even when adjusted for confounding variables. CONCLUSIONS: Our results suggest that TC theory may be a useful framework for explaining body satisfaction in the elderly. Studies on this subject should be encouraged. However, further research is needed before any conclusion can be drawn.

OBJETIVOS: Estudos sobre a satisfação corporal têm negligenciado uma possível contribuição da teoria de comparação temporal a fim de determinar a percepção que os idosos têm do próprio corpo. O objetivo deste trabalho é estudar a utilidade da teoria de comparação temporal na determinação da satisfação corporal de idosos. MÉTODOS: Dezoito idosos, com idade entre 68 e 90 anos, e possuindo certo grau de limitação física, participaram do estudo. Depois de receberem estímulos relacionados a três teorias (comparação social, comparação temporal e self-schema), os participantes completaram uma escala de satisfação com a função física e uma escala de satisfação com a aparência. RESULTADOS: A satisfação corporal não diferiu entre os estímulos relacionados às três teorias aplicadas. Correlações relacionadas à teoria de comparação temporal foram superiores às correlações relacionadas às outras teorias, mesmo quando as correlações foram ajustadas por certas variáveis de confusão. CONCLUSÕES: Estes resultados sugerem que a teoria CT parece ser útil para explicar a satisfação corporal de idosos. Estudos sobre este assunto devem ser encorajados a fim que se possam desenhar conclusões sobre bases sólidas.