The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults. Plasma GDF15 levels were measured using immunoassays in 302 older adults (≥65 years) admitted to the emergency department (ED). Nutritional status was evaluated with the Mini Nutritional Assessment Short-Form (MNA®-SF), appetite was evaluated with the Simplified Nutritional Appetite Questionnaire (SNAQ), and physical function was evaluated with handgrip strength (HGS), 30-s chair stand test (30s-RSS), and gait speed (GS). Associations between GDF15 and each outcome was determined by logistic regression adjusted for age, sex, and C-reactive protein (CRP). Each doubling in plasma GDF15 level was associated with an adjusted odds ratio (OR) (95% confidence interval) of 1.59 (1.10-2.29, P = 0.01) for risk of malnutrition compared to normal nutrition and 1.19 (0.85-1.69, P = 0.3)) for malnutrition compared to risk of malnutrition. Each doubling in GDF15 was associated with an adjusted OR of 1.63 (1.21-2.23)) for having poor appetite, 1.46 (1.07-1.99) for having low HGS, 1.74 (1.23-2.51) for having low 30s-RSS, and 1.99 (1.39-2.94) for having low GS. Among older adults admitted to the ED, higher GDF15 levels were significantly associated with malnutrition, poor appetite, and low physical function independent of age, sex, and CRP.

Malnutrition, risk of malnutrition, and risk factors for malnutrition are prevalent among acutely admitted medical patients aged ≥65 years and have significant health-related consequences. Consequently, we aimed to investigate the effectiveness of a multidisciplinary and transitional nutritional intervention on health-related quality of life compared with standard care. The study was a block randomized, observer-blinded clinical trial with two parallel arms. The Intervention Group was offered a multidisciplinary transitional nutritional intervention consisting of dietary counselling and six sub-interventions targeting individually assessed risk factors for malnutrition, while the Control Group received standard care. The inclusion criteria were a Mini Nutritional Assessment Short-Form score ≤11, age ≥65 years, and an acute admittance to the Emergency Department. Outcomes were assessed on admission and 8 and 16 weeks after hospital discharge. The primary outcome was the difference between groups in change in health-related quality of life (assessed by the EuroQol-5D-5L) from baseline to 16 weeks after discharge. The secondary outcomes were difference in intake of energy and protein, well-being, muscle strength, and body weight at all timepoints. From October 2018 to April 2021, 130 participants were included. Sixteen weeks after discharge, 29% in the Intervention Group and 19% in the Control Group were lost to follow-up. Compliance varied between the sub-interventions targeting nutritional risk factors and was generally low after discharge, ranging from 0 to 61%. No difference was found between groups on change in health-related quality of life or on well-being, muscle strength, and body weight at any timepoint, neither using the intention-to-treat analysis nor the per-protocol analysis. The protein intake was higher in the Intervention Group during hospitalization (1.1 (Standard Deviation (SD) 0.4) vs 0.8 (SD 0.5) g/kg/day, p = 0.0092) and 8 weeks after discharge (1.2 (SD 0.5) vs 0.9 (0.4) g/kg/day, p = 0.0025). The percentual intake of calculated protein requirements (82% (SD 24) vs 61% (SD 32), p = 0.0021), but not of calculated energy requirements (89% (SD 23) vs 80% (SD 37), p = 0.2), was higher in the Intervention Group than in the Control Group during hospitalization. Additionally, the Intervention Group had a significantly higher percentual intake of calculated protein requirements (94% (SD 41) vs 74% (SD 30), p = 0.015) and calculated energy requirements (115% (SD 37) vs 94% (SD 31), p = 0.0070) 8 weeks after discharge. The intake of energy and protein was comparable between the groups 16 weeks after discharge. We found no effect of a multidisciplinary and transitional nutritional intervention for acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition on our primary outcome, health-related quality of life 16 weeks after discharge. Nor did the intervention affect the secondary outcomes, well-being, muscle strength, and body weight from admission to 8 or 16 weeks after discharge. However, the intervention improved energy and protein intake during hospitalization and 8 weeks after discharge. Low compliance with the intervention after discharge may have compromised the effect of the intervention. The study is registered at ClinicalTrials.gov (identifier: NCT03741283).

The accuracy of multi-frequency (MF) bioelectrical impedance analysis (BIA) to estimate low muscle mass in older hospitalized patients remains unclear. This study aimed to describe the ability of MF-BIA to identify low muscle mass as proposed by The Global Leadership Initiative on Malnutrition (GLIM) and The European Working Group on Sarcopenia in Older People (EWGSOP-2) and examine the association between muscle mass, dehydration, malnutrition, and poor appetite in older hospitalized patients. In this prospective exploratory cohort study, low muscle mass was estimated with MF-BIA against dual-energy X-ray absorptiometry (DXA) in 42 older hospitalized adults (≥65 years). The primary variable for muscle mass was appendicular skeletal muscle mass (ASM), and secondary variables were appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI). Cut-off values for low muscle mass were based on recommendations by GLIM and EWGSOP-2. MF-BIA was evaluated against DXA on the ability to estimate absolute values of muscle mass by mean bias, limits of agreement (LOA), and accuracy (5% and 10% levels). Agreement between MF-BIA and DXA to identify low muscle mass was evaluated with sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The association between muscle mass, dehydration, malnutrition, and poor appetite was visually examined with boxplots. MF-BIA overestimated absolute values of ASM with a mean bias of 0.63 kg (CI: −0.20:1.46, LOA: −4.61:5.87). Agreement between MF-BIA and DXA measures of ASM showed a sensitivity of 86%, specificity of 94%, PPV of 75% and NPV of 97%. Boxplots indicate that ASM is lower in patients with malnutrition. This was not observed in patients with poor appetite. We observed a tendency toward higher ASM in patients with dehydration. Estimation of absolute ASM values with MF-BIA should be interpreted with caution, but MF-BIA might identify low muscle mass in older hospitalized patients.

In acutely hospitalized older patients (≥65 years), the association between mild cognitive impairment (MCI) and malnutrition is poorly described. We hypothesized that (1) MCI is associated with nutritional status on admission and after discharge; (2) MCI is associated with a change in nutritional status; and (3) a potential association is partly explained by frailty, comorbidity, medication use, and age. We combined data from a randomized controlled trial (control group data) and a prospective cohort study (ClinicalTrials.gov: NCT01964482 and NCT03052192). Nutritional status was assessed on admission and follow-up using the Mini Nutritional Assessment—Short Form. MCI or intact cognition (noMCI) was classified by three cognitive performance tests at follow-up. Data on frailty, comorbidity, medication use, and age were drawn from patient journals. MCI (n = 42) compared to noMCI (n = 47) was associated with poorer nutritional status with an average difference of −1.29 points (CI: −2.30; −0.28) on admission and −1.64 points (CI: −2.57; −0.70) at 4-week follow-up. Only age influenced the estimates of −0.85 (CI: −1.86; 0.17) and −1.29 (CI: −2.25; −0.34), respectively. In acutely hospitalized older patients, there is an association between MCI and poorer nutritional status upon admission and four weeks after discharge. The association is partly explained by higher age.

Anorexia of aging is prevalent and constitutes a significant factor in the onset of malnutrition with limited effective interventions. Cannabis-based medicine (CBM) with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may have orexigenic properties in older patients with poor appetite. However, current evidence is insufficient regarding the impact of CBM in older patients with poor appetite. This trial aimed to assess the difference in caloric intake between an oromucosal spray containing CBM versus placebo. The secondary outcomes were safety parameters (tiredness, vertigo, nausea, euphoria, blood pressure, and heart rate). The trial is an investigator-initiated single-center, triple-blinded, randomized, placebo-controlled, superiority, cross-over trial with 17 patients ≥65 years with poor appetite. Patients received two dosages of CBM (8.1 mg THC and 7.5 mg CBD pr dosage) and placebo at two time points on two separate trial days, with a two-week washout period between trial days. The primary outcome, caloric intake, was measured with a controlled feeding study using standardized homogenous test meals. Safety parameters were assessed with 100 mm numerical visual analog scales. No statically significant difference in mean caloric intake between CBM and placebo was observed (10 kilocalories (kcal) (CI: -55-75 kcal), favoring CBM). During the trial, 36 adverse events were classified as unrelated to CBM, while 16 were classified as possibly-related. Of the 16 possibly-related, five were during placebo conditions and one was reported prior to CBM. All possibly-related adverse events were mild and transient. No serious related adverse events were observed. In older patients with poor appetite, CBM administered buccally at two time points at the same day, with each dose containing 8.1 mg THC and 7.5 mg CBD, did not improve caloric intake compared to placebo. The observed safety parameters suggest that CBM is generally tolerated when administered according to this dosing regimen. The trial was registered at EudraCT (2021-002318-15) and Clinicaltrials. gov (NCT05503147).

Poor appetite is a key contributor to malnutrition in older adults, partly due to reduced dietary intake. While nutritional deficits are well recognized, the biological mechanisms driving poor appetite remain incompletely understood. Growth Differentiation Factor-15 (GDF-15) and the Simplified Nutritional Appetite Questionnaire (SNAQ) may help identify patients at risk of insufficient intake. This study examines the association between GDF-15 and insufficient energy and protein intake and evaluates the predictive performance of GDF-15 and SNAQ - individually and in combination - to identify insufficient energy and protein intake (<75 % and <100 % of estimated requirements, respectively) in acutely admitted older adults. This exploratory study included 130 older adults (≥65 years) with or at risk of malnutrition, admitted for acute medical illness and assessed at baseline, and 8 and 16 weeks post-discharge (FW8 and FW16). GDF-15 plasma concentrations were measured from blood samples, SNAQ scores from validated questionnaire, and energy and protein intake were evaluated through 3-day dietary records. Associations were analyzed using regression models and predictive performance was evaluated using Receiver Operating Characteristic analysis. A doubling of GDF-15 showed a 6.73 % (-13.98-0.51) and 5.07 % (-12.18-2.05) lower baseline energy and protein intake, and results decreased after discharge. Using predefined cut-offs of ≥1500 pg/mL for GDF-15 and ≤14 for SNAQ, the highest positive predictive values (PPVs) were 86 (95 % CI: 0.83-0.89) and 90 (0.79-1.00) at baseline and FW8 for insufficient protein intake, respectively, with corresponding sensitivities of 84 (0.75-0.92) and 60 (0.44-0.74). For estimated cut-offs of 2095 pg/mL for GDF-15 at baseline and 18.5 for SNAQ at FW8, the highest PPVs were 89 (0.84-0.94) and 87 (0.86-0.87), with sensitivities of 73 (0.62-0.84) and 99 (0.96-1.00), both for insufficient protein intake, respectively. Combining GDF-15 and SNAQ yielded improved PPVs at the expense of reduced sensitivity in most models. All results were non-significant. Higher GDF-15 levels showed a non-significant trend toward lower baseline energy and protein intake. GDF-15 and SNAQ offer limited ability to identify insufficient energy and protein intake, based on predictive performance. These exploratory findings should therefore be interpreted cautiously. Larger studies are needed to validate and further refine the use of GDF-15 and SNAQ in clinical settings.