Acoustic stimulation as a promising technique to enhance slow-wave sleep in Alzheimer's disease: results of a pilot study.

STUDY OBJECTIVES: Sleep disturbances are common in people with Alzheimer's disease (AD), and a reduction in slow-wave activity is the most striking underlying change. Acoustic stimulation has emerged as a promising approach to enhance slow-wave activity in healthy adults and people with amnestic mild cognitive impairment. In this phase 1 study we investigated, for the first time, the feasibility of acoustic stimulation in AD and piloted the effect on slow-wave sleep (SWS). METHODS: Eleven adults with mild to moderate AD first wore the DREEM 2 headband for 2 nights to establish a baseline registration. Using machine learning, the DREEM 2 headband automatically scores sleep stages in real time. Subsequently, the participants wore the headband for 14 consecutive "stimulation nights" at home. During these nights, the device applied phase-locked acoustic stimulation of 40-dB pink noise delivered over 2 bone-conductance transducers targeted to the up-phase of the delta wave or SHAM, if it detected SWS in sufficiently high-quality data. RESULTS: Results of the DREEM 2 headband algorithm show a significant average increase in SWS (minutes) [t(3.17) = 33.57, P = .019] between the beginning and end of the intervention, almost twice as much time was spent in SWS. Consensus scoring of electroencephalography data confirmed this trend of more time spent in SWS [t(2.4) = 26.07, P = .053]. CONCLUSIONS: Our phase 1 study provided the first evidence that targeted acoustic stimuli is feasible and could increase SWS in AD significantly. Future studies should further test and optimize the effect of stimulation on SWS in AD in a large randomized controlled trial. CITATION: Van den Bulcke L, Peeters A-M, Heremans E, et al. Acoustic stimulation as a promising technique to enhance slow-wave sleep in Alzheimer's disease: results of a pilot study. J Clin Sleep Med. 2023;19(12):2107-2112.

Physiologically based pharmacokinetic (PBPK) modelling of oral drug absorption in older adults - an AGePOP review.

The older population consisting of persons aged 65 years or older is the fastest-growing population group and also the major consumer of pharmaceutical products. Due to the heterogenous ageing process, this age group shows high interindividual variability in the dose-exposure-response relationship and, thus, a prediction of drug safety and efficacy is challenging. Although physiologically based pharmacokinetic (PBPK) modelling is a well-established tool to inform and confirm drug dosing strategies during drug development for special population groups, age-related changes in absorption are poorly accounted for in current PBPK models. The purpose of this review is to summarise the current state-of-knowledge in terms of physiological changes with increasing age that can influence the oral absorption of dosage forms. The capacity of common PBPK platforms to incorporate these changes and describe the older population is also discussed, as well as the implications of extrinsic factors such as drug-drug interactions associated with polypharmacy on the model development process. The future potential of this field will rely on addressing the gaps identified in this article, which can subsequently supplement in-vitro and in-vivo data for more robust decision-making on the adequacy of the formulation for use in older adults and inform pharmacotherapy.

Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? - Exploratory results from ENHANce.

AIMS: To explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults. METHODS: The Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman's rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS: In total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8-5.6 g/d; ♀:2.2-4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024). CONCLUSIONS: Although intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.

The effect of a trAnSitional Pharmacist Intervention in geRiatric inpatients on hospital visits after dischargE (ASPIRE): Protocol for a randomized controlled trial.

BACKGROUND: Unplanned rehospitalizations occur frequently in older patients. Drug-related problems constitute a major and largely preventable cause with inappropriate prescribing being a substantial culprit. Solutions are needed to reduce this risk by targeting pharmacotherapy both during and after hospital stay. Therefore, we aim to perform a randomized controlled trial in geriatric inpatients to investigate the impact of a multifaceted clinical pharmacy intervention on health-related outcomes. METHODS/DESIGN: The study concerns a monocenter, non-blinded, randomized controlled trial that will take place at the acute geriatric wards of a large academic hospital. Patients being in a palliative stage with active therapy withdrawal or patients discharged to another ward within the same hospital or another hospital are excluded. In total, 828 patients will be randomized (1:1) to the usual care or intervention group. The multifaceted clinical pharmacy intervention comprises medication reconciliation at admission and discharge, medication review, patient/caregiver education, intensified communication with primary care providers and post-discharge follow-up, which also includes a telepharmacology service. The primary endpoint is defined as the time to an all-cause, unplanned hospital revisit within six months after discharge. Other health-related outcomes such as drug-related readmissions, quality of life and number of potentially inappropriate medications will be analyzed as secondary endpoints. Patient inclusion started in February 2021. DISCUSSION: This study will provide useful insights regarding the impact of clinical pharmacy interventions on geriatric wards with the goal to optimize health-related outcomes such as hospital revisits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04617340.

Exercise and Nutrition for Healthy AgeiNg (ENHANce) project - effects and mechanisms of action of combined anabolic interventions to improve physical functioning in sarcopenic older adults: study protocol of a triple blinded, randomized controlled trial.

BACKGROUND: The Exercise and Nutrition for Healthy AgeiNg (ENHANce) project aims to assess the combined effects of exercise and nutritional interventions to prevent loss of skeletal muscle mass and function with ageing, and to determine the underlying mechanisms of action. METHODS: One hundred eightycommunity-dwelling sarcopenic individuals (≥ 65 years) are allocated in a randomized controlled trial (RCT) in a 1:1 ratio into five groups for a 12-week intervention period, followed by a 12-week follow-up period: 1) exercise intervention +protein placebo +omega-3 fatty acids placebo; 2) protein +omega-3 fatty acids placebo; 3) exercise intervention +protein +omega-3 fatty acids placebo; 4) exercise intervention +protein +omega-3 fatty acids; 5) protein placebo +omega-3 fatty acids placebo. All interventions are in line with recommendations of expert groups such as the American College of Sports Medicine and the PROT-AGE study group and individualized to the physical capabilities and nutritional intake of each participant. Sarcopenia is diagnosed by the assessment of gait speed, handgrip strength (Jamar handheld dynamometer), chair stand test and muscle mass (DXA) according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Participants, researchers and statisticians are blinded to omega-3 fatty acids and protein treatment. Compliance to the exercise program, protein and omega-3 fatty acids interventions is objectively measured, by monitoring movement by an activity monitor, determining nitrogen content in urine and analyzing the fatty acid composition of the red blood cell membrane. The primary outcome of the RCT is the change in Short Physical Performance Battery (SPPB) score. Secondary endpoints are, among others, changes in muscle mass, strength and function, objective compliance to interventions, changes in muscle and blood biomarkers related to sarcopenia, cognition, quality of life and falls. DISCUSSION: This RCT in well-defined sarcopenic older adults assesses the effects of combined anabolic interventions, including the additive effects of omega-3 fatty acids supplements, compared to single or placebo interventions. Compliance with the exercise intervention and with the intake of nutritional supplements is measured objectively. Also, blood and muscle samples will be used to explore the underlying determinants that contribute to the mechanism of action of anabolic interventions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03649698 , retrospectively registered at 28 August 2018, first participant was randomized 16 February 2018.

Effects of multi-domain interventions in (pre)frail elderly on frailty, functional, and cognitive status: a systematic review.

BACKGROUND: Frailty is an aging syndrome caused by exceeding a threshold of decline across multiple organ systems leading to a decreased resistance to stressors. Treatment for frailty focuses on multi-domain interventions to target multiple affected functions in order to decrease the adverse outcomes of frailty. No systematic reviews on the effectiveness of multi-domain interventions exist in a well-defined frail population. OBJECTIVES: This systematic review aimed to determine the effect of multi-domain compared to mono-domain interventions on frailty status and score, cognition, muscle mass, strength and power, functional and social outcomes in (pre)frail elderly (≥65 years). It included interventions targeting two or more domains (physical exercise, nutritional, pharmacological, psychological, or social interventions) in participants defined as (pre)frail by an operationalized frailty definition. METHODS: The databases PubMed, EMBASE, CINAHL, PEDro, CENTRAL, and the Cochrane Central register of Controlled Trials were searched from inception until September 14, 2016. Additional articles were searched by citation search, author search, and reference lists of relevant articles. The protocol for this review was registered on PROSPERO (CRD42016032905). RESULTS: Twelve studies were included, reporting a large diversity of interventions in terms of content, duration, and follow-up period. Overall, multi-domain interventions tended to be more effective than mono-domain interventions on frailty status or score, muscle mass and strength, and physical functioning. Results were inconclusive for cognitive, functional, and social outcomes. Physical exercise seems to play an essential role in the multi-domain intervention, whereby additional interventions can lead to further improvement (eg, nutritional intervention). CONCLUSION: Evidence of beneficial effects of multi-domain compared to mono-domain interventions is limited but increasing. Additional studies are needed, focusing on a well-defined frail population and with specific attention to the design and the individual contribution of mono-domain interventions. This will contribute to the development of more effective interventions for frail elderly.