Metabolic dysfunction and dysregulation of leptin signaling have been linked to Alzheimer’s Disease (AD)’s pathophysiology. The objectives of this study were to examine the associations between plasma leptin, cerebrospinal fluid (CSF) beta-amyloid (Aβ) and tau biomarkers (AT(N) status) and with the stage of cognitive impairment. Cross-sectional analysis of data from cognitively impaired patients from a tertiary memory clinic. Plasma leptin levels were compared according to the stage of cognitive impairment and biomarker profiles, using the AT(N) classification. Linear regression models were performed to examine the relationship between leptin and CSF biomarkers. Results were adjusted for age, gender, body mass index (BMI) and APOE ε4. In a subgroup of A+T+ individuals, we compared the 2-year evolution of Mini Mental Status scores, according to the participants’ tertile of plasma leptin levels. We included 1036 participants (age 68.7±9.1, females=54.1%). A+T+ and A+T- patients had significantly lower plasma leptin levels than amyloid negative subjects (p<0.01). CSF Aβ concentration was significantly associated with lower plasma leptin β= -4.3 (1.5), p=0.005 unadjusted; and β= -3.4 (1.6), p=0.03 after adjustment for age, female gender, BMI and APOE ε4. Patients with major neurocognitive disorder due to AD had a difference of leptin of -7.3 ng/ml 95%CI[-11.8;-2.8],p=0.0002, compared to individuals with other causes of cognitive impairment. Leptin was not associated with the slope of cognitive decline. Plasma leptin levels were associated with CSF Aβ and with the diagnosis of AD confirmed by CSF biomarkers, suggesting a molecular interplay between leptin metabolism and brain amyloid deposition.

OBJECTIVE: Telomere shortening and DNA oxidation are associated with premature vascular aging, which may be involved in lower-extremity amputation (LEA). We sought to investigate whether leukocyte telomere length (LTL) and plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation, were associated with LEA in subjects with type 1 diabetes at high vascular risk. RESEARCH DESIGN AND METHODS: LTL (quantitative PCR) and plasma 8-OHdG concentrations (immunoassay method) were assessed at baseline in the GENEDIAB (Génétique de la Néphropathie Diabétique) type 1 diabetes cohort. Logistic and Cox proportional hazards regression models were fitted to estimate odds ratio (OR) (at baseline) and hazard ratio (HR) (during follow-up), with related 95% CI, by increasing biomarker tertiles (T1, T2, T3). RESULTS: Among 478 participants (56% male, mean ± SD age 45 ± 12 years and diabetes duration 29 ± 10 years), 84 patients had LEA at baseline. Baseline history of LEA was associated with shorter LTL (OR for T2 vs. T1 0.62 [95% CI 0.32–1.22] and for T3 vs. T1 0.41 [0.20–0.84]) but not with plasma 8-OHdG (1.16 [0.56–2.39] and 1.24 [0.61–2.55], respectively). New cases of LEA occurred in 34 (12.3%) participants during the 10-year follow-up. LTL were shorter (HR T2 vs. T1 0.25 [95% CI 0.08–0.67] and T3 vs. T1 0.29 [0.10–0.77]) and plasma 8-OHdG higher (2.20 [0.76–7.35] and 3.11 [1.07–10.32]) in participants who developed LEA during follow-up compared with others. No significant interaction was observed between biomarkers on their association with LEA. CONCLUSIONS: We report the first independent association between LTL shortening and excess risk of LEA in type 1 diabetes. High plasma 8-OHdG was also associated with incident LEA but partly dependent on cofounding variables.

Background: Type 1 diabetes is associated with accelerated vascular aging and advanced atherosclerosis resulting in increased rates of cardiovascular disease and premature death. We evaluated associations between Leukocyte telomere length (LTL), allelic variations (SNPs) in LTL-related genes and the incidence of coronary heart disease (CHD) in adults with long-standing type 1 diabetes. Methods: We assessed associations of LTL, measured at baseline by RT–PCR, and of SNPs in 11 LTL-related genes with the risk of coronary heart disease (CHD: myocardial infarction or coronary revascularization) and all-cause death during follow-up in two multicenter French-Belgian prospective cohorts of people with long-standing type 1 diabetes. Results: In logistic and Cox analyses, the lowest tertile of LTL distribution (short telomeres) at baseline was associated with the prevalence of myocardial infarction at baseline and with increased risk of CHD (Hazard ratio 3.14 (1.39–7.70), p = 0.005, for shorter vs longer tertile of LTL) and all-cause death (Hazard ratio 1.63 (95% CI 1.04–2.55), p = 0.03, for shorter vs combined intermediate and longer tertiles of LTL) during follow-up. Allelic variations in six genes related to telomere biology (TERC, NAF1, TERT, TNKS, MEN1 and BICD1) were also associated with the incidence of CHD during follow-up. The associations were independent of sex, age, duration of diabetes, and a range of relevant confounding factors at baseline. Conclusions: Our results suggest that short LTL is an independent risk factor for CHD in people with type 1 diabetes.

Background: In older adults, physical activity (PA) is important in maintaining physical performance. Data on the effectiveness of public open-access community-based programs on physical performance and fall prevention are scarce. Methods: Prospective observational controlled study in community centers providing an open-access public prevention program. Retirees aged ≥60 years who chose to participate in weekly PA workshops for 3 months were compared to those who chose the cognitive stimulation (CS) workshops. Collected data: handgrip strength, five times sit-to-stand, single-leg stance, Timed Up and Go tests, gait speed, short physical performance battery (SPPB) and frailty status at baseline (M0) and at 3 months (M3). The proportion of participants reporting a history of falls was assessed at baseline and using follow-up telephone interviews (F-Up). Results: Two hundred eighty-eight participants (age 73.8 years, 87% women) were included. The sit-to-stand test, single-leg stance and SPPB scores improved significantly between M0 and M3 in both groups. A greater SPPB increase was observed in the PA than in the CS group (+0.39 vs. +0.32 points, P = 0.02) after adjustment for age, sex, number of sessions attended, fall history and SPPB at baseline. During F-Up (median 22 months), the proportion of participants reporting at least one fall decreased from 55% to 31% (P = 0.01) in the PA group and from 27% to 19% (P = 0.12) in the CS group. Conclusion: In a public open-access community-based program participants improved physical performance and reduced fall incidence when participating in the PA or the CS workshops. Older adults may benefit most from multifaceted prevention programs.

Background: Every year in France, 40% of people aged ≥80 years are hospitalized, with an average length of hospital stay of 25 days and a readmission rate of 14% to 30% within the month following discharge. This situation is putting pressure on the health care system, encouraging the reinforcement of home care to reduce avoidable hospitalization. The EPOCA remote patient monitoring (RPM) system is a medical and social telehealth solution specialized in RPM, teleconsultation, tele-expertise, and care coordination in emergency medicine and geriatrics. The platform provides long-term medical support at home (MSAH) with 24-7 telemonitoring of older adults with polypathology. We hypothesized that receiving long-term MSAH via the EPOCA RPM system would be associated with a reduction in the rates and durations of hospitalizations or emergency department (ED) visits in older adults with polypathology. Objective: We aimed to compare the hospitalization and ED visit rates, as well as the cumulative hospital stay duration, before and after enrollment in the EPOCA RPM system for older adults with polypathology. Methods: This retrospective observational study included older adults (aged ≥70 years) with polypathology (>2 affected systems) followed throughout 2 different types of long-term MSAH between February 2022 and October 2023. We compared the number of hospital admissions, including ED visits; the cumulative duration of hospital stays during the follow-up; and the average length of hospital stays during the period corresponding to the MSAH program (Y) compared to the year before entering the program (Y – 1). Subgroup analyses were conducted according to the severity of the participants’ disability. Results: A total of 120 participants were included in the MSAH program, with a mean age of 86.8 (SD 7.9) years. Hospitalization and ED visit rates decreased (−48%) between the Y – 1 and Y periods, as did the total duration of hospital stays (−63%). A significant reduction in number of hospitalizations (median decreased from 1.0 to 0.0 per patient per year; P<.001) and ED visits (median decreased from 1.0 to 0.0 per patient per year; P<.001) was observed between the Y – 1 and Y periods. This corresponded to a significant median reduction of 14 days spent at the hospital per patient per year (P<.001). The decrease in hospitalization and ED visit rates and numbers was greater in participants with severe disabilities than in those with no or moderate disabilities. Conclusions: Among older adults with polypathology, the EPOCA RPM system is associated with reduction in number of hospitalizations, ED visits, and duration of hospital stays. Facing the challenge of population aging, home telemonitoring embedded in the health care system offers potential benefits.

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8–12), and median WS 1.09 (IQR: 0.9–1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3–4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2–26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.