Multi-night acoustic stimulation is associated with better sleep, amyloid dynamics, and memory in older adults with cognitive impairment.

Sleep is a potential early, modifiable risk factor for cognitive decline and dementia. Impaired slow wave sleep (SWS) is pronounced in individuals with cognitive impairment (CI). Cognitive decline and impairments of SWS are bi-directionally linked in a vicious cycle. SWS can be enhanced non-invasively using phase-locked acoustic stimulation (PLAS), potentially breaking this vicious cycle. Eighteen healthy older adults (HC, agemean±sd, 68.3 ± 5.1) and 16 older adults (agemean±sd, 71.9 ± 3.9) with CI (Montreal Cognitive Assessment ≤ 25) underwent one baseline (sham-PLAS) night and three consecutive stimulation nights (real-PLAS). EEG responses and blood-plasma amyloid beta Aß42/Aß40 ratio were measured pre- and post-intervention, as was episodic memory. The latter was again evaluated 1 week and 3 months after the intervention. In both groups, PLAS induced a significant electrophysiological response in both voltage- and time-frequency analyses, and memory performance improved in association with the magnitude of this response. In the CI group, both electrophysiological and associated memory effects were delayed compared to the healthy group. After 3 intervention nights, electrophysiological response to PLAS was no longer different between CI and HC groups. Only in the CI sample, stronger electrophysiological responses were significantly associated with improving post-intervention Aß42/Aß40 ratios. PLAS seems to improve SWS electrophysiology, memory, and amyloid dynamics in older adults with CI. However, effects on memory require more time to unfold compared to healthy older adults. This indicates that PLAS may become a potential tool to ameliorate cognitive decline, but longer interventions are necessary to compensate for declining brain integrity. This study was pre-registered (clinicaltrials.gov: NCT04277104).

[Recommendations for the diagnostic and therapy of behavioural and psychological symptoms of dementia (BPSD)].

INTRODUCTION: The «Recommendations for the Diagnosis and Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD)¼ were developed in parallel with the Swiss National Dementia Strategy 2014-2019 under the auspices of the Swiss Society for Geriatric Psychiatry and Psychotherapy (SGAP) and mark the beginning of a series of recommendations for geriatric psychiatric disorders. They depict the evidence-based state of knowledge about diagnostics and therapy, based on the clinical experience of the experts, and are designed for interprofessional and interdisciplinary use. The non-pharmacological intervention options and pharmacotherapy are discussed in detail. This paper is the revised version of the 2014 publication and compiles the development in this area for everyday clinical practice.

A Transferable Lidar-Based Method to Conduct Contactless Assessments of Gait Parameters in Diverse Home-like Environments.

Gait abnormalities in older adults are linked to increased risks of falls, institutionalization, and mortality, necessitating accurate and frequent gait assessments beyond traditional clinical settings. Current methods, such as pressure-sensitive walkways, often lack the continuous natural environment monitoring needed to understand an individual's gait fully during their daily activities. To address this gap, we present a Lidar-based method capable of unobtrusively and continuously tracking human leg movements in diverse home-like environments, aiming to match the accuracy of a clinical reference measurement system. We developed a calibration-free step extraction algorithm based on mathematical morphology to realize Lidar-based gait analysis. Clinical gait parameters of 45 healthy individuals were measured using Lidar and reference systems (a pressure-sensitive walkway and a video recording system). Each participant participated in three predefined ambulation experiments by walking over the walkway. We observed linear relationships with strong positive correlations (R2>0.9) between the values of the gait parameters (step and stride length, step and stride time, cadence, and velocity) measured with the Lidar sensors and the pressure-sensitive walkway reference system. Moreover, the lower and upper 95% confidence intervals of all gait parameters were tight. The proposed algorithm can accurately derive gait parameters from Lidar data captured in home-like environments, with a performance not significantly less accurate than clinical reference systems.

Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T.

GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml. Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively. Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus). Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1--inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio. Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012). Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18-27 min (GABA+) and 9-18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

Cognitive behavioural therapy (CBT) with and without exercise to reduce fear of falling in older people living in the community.

BACKGROUND: Fear of falling (FoF) is a lasting concern about falling that leads to an individual avoiding activities that he/she remains capable of performing. It is a common condition amongst older adults and may occur independently of previous falls. Cognitive behavioural therapy (CBT), a talking therapy that helps change dysfunctional thoughts and behaviour, with and without exercise, may reduce FoF, for example, by reducing catastrophic thoughts related to falls, and modifying dysfunctional behaviour. OBJECTIVES: To assess the benefits and harms of CBT for reducing FoF in older people living in the community, and to assess the effects of interventions where CBT is used in combination with exercise. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2023), MEDLINE Ovid (from 1946 to 11 January 2023), Embase Ovid (from 1980 to 11 January 2023), CINAHL Plus (Cumulative Index to Nursing and Allied Health Literature) (from 1982 to 11 January 2023), PsycINFO (from 1967 to 11 January 2023), and AMED (Allied and Complementary Medicine from 1985 to 11 January 2023). We handsearched reference lists and consulted experts for identifying additional studies. SELECTION CRITERIA: This review included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs assessing CBT with and without exercise interventions compared to control groups with sham-treatment, or treatment as usual. We defined CBT as a collaborative, time-limited, goal-oriented, and structured form of speaking therapy. Included studies recruited community-dwelling older adults, with a mean population age of at least 60 years minus one standard deviation, and not defined by a specific medical condition. DATA COLLECTION AND ANALYSIS: Two review authors used standard methodological procedures expected by Cochrane. For continuous data, as assessed by single- or multiple-item questionnaires, we report the mean difference (MD) with 95% confidence interval (CI) when studies used the same outcome measures, and standardised mean difference (SMD) when studies used different measures for the same clinical outcome. For dichotomous outcomes, we reported the treatment effects as risk ratios (RR) with 95% CIs. We measured the primary outcome, FoF, immediately, up to, and more than six months after the intervention. We analysed secondary outcomes of activity avoidance, occurrence of falls, depression, and quality of life when measured immediately after the intervention. We assessed risk of bias for each included study, using the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We selected 12 studies for this review, with 11 studies included for quantitative synthesis. One study could not be included due to missing information. Of the 11 individual studies, two studies provided two comparisons, which resulted in 13 comparisons. Eight studies were RCTs, and four studies were cluster-RCTs. Two studies had multiple arms (CBT only and CBT with exercise) that fulfilled the inclusion criteria. The primary aim of 10 studies was to reduce FoF. The 11 included studies for quantitative synthesis involved 2357 participants, with mean ages between 73 and 83 years. Study total sample sizes varied from 42 to 540 participants. Of the 13 comparisons, three investigated CBT-only interventions while 10 investigated CBT with exercise. Intervention duration varied between six and 156 hours, at a frequency between three times a week and monthly over an eight- to 48-week period. Most interventions were delivered in groups of between five and 10 participants, and, in one study, up to 25 participants. Included studies had considerable heterogeneity, used different questionnaires, and had high risks of bias. CBT interventions with and without exercise probably improve FoF immediately after the intervention (SMD -0.23, 95% CI -0.36 to -0.11; 11 studies, 2357 participants; moderate-certainty evidence). The sensitivity analyses did not change the intervention effect significantly. Effects of CBT with or without exercise on FoF may be sustained up to six months after the intervention (SMD -0.24, 95% CI -0.41 to -0.07; 8 studies, 1784 participants; very low-certainty evidence). CBT with or without exercise interventions for FoF probably sustains improvements beyond six months (SMD -0.28, 95% CI -0.40 to -0.15; 5 studies, 1185 participants; moderate-certainty of evidence). CBT interventions for reducing FoF may reduce activity avoidance (MD -2.57, 95% CI -4.67 to -0.47; 1 study, 312 participants; low-certainty evidence), and level of depression (SMD -0.41, 95% CI -0.60 to -0.21; 2 studies, 404 participants; low-certainty evidence). We are uncertain whether CBT interventions reduce the occurrence of falls (RR 0.96, 95% CI 0.66 to 1.39; 5 studies, 1119 participants; very low-certainty evidence). All studies had a serious risk of bias, due to performance bias, and at least an unclear risk of detection bias, as participants and assessors could not be blinded due to the nature of the intervention. Downgrading of certainty of evidence also occurred due to heterogeneity between studies, and imprecision, owing to limited sample size of some studies. There was no reporting bias suspected for any article. No studies reported adverse effects due to their interventions. AUTHORS' CONCLUSIONS: CBT with and without exercise interventions probably reduces FoF in older people living in the community immediately after the intervention (moderate-certainty evidence). The improvements may be sustained during the period up to six months after intervention (low-certainty evidence), and probably are sustained beyond six months (moderate-certainty evidence). Further studies are needed to improve the certainty of evidence for sustainability of FoF effects up to six months. Of the secondary outcomes, we are uncertain whether CBT interventions for FoF reduce the occurrence of falls (very low-certainty evidence). However, CBT interventions for reducing FoF may reduce the level of activity avoidance, and may reduce depression (low-certainty evidence). No studies reported adverse effects. Future studies could investigate different populations (e.g. nursing home residents or people with comorbidities), intervention characteristics (e.g. duration), or comparisons (e.g. CBT versus exercise), investigate adverse effects of the interventions, and add outcomes (e.g. gait analysis). Future systematic reviews could search specifically for secondary outcomes.

The moderating effects of sex, age, and education on the outcome of combined cognitive training and transcranial electrical stimulation in older adults.

Computerized cognitive training (CCT) has been shown to improve cognition in older adults via targeted exercises for single or multiple cognitive domains. Combining CCT with non-invasive brain stimulation is thought to be even more effective due to synergistic effects in the targeted brain areas and networks. However, little is known about the moderating effects of sex, age, and education on cognitive outcomes. Here, we investigated these factors in a randomized, double-blind study in which we administered CCT either combined with transcranial direct (tDCS), alternating (tACS) current stimulation or sham stimulation. 59 healthy older participants (mean age 71.7 ± 6.1) received either tDCS (2 mA), tACS (5 Hz), or sham stimulation over the left dorsolateral prefrontal cortex during the first 20 min of a CCT (10 sessions, 50 min, twice weekly). Before and after the complete cognitive intervention, a neuropsychological assessment was performed, and the test scores were summarized in a composite score. Our results showed a significant three-way interaction between age, years of education, and stimulation technique (F(6,52) = 5.53, p = 0.007), indicating that the oldest participants with more years of education particularly benefitted from tDCS compared to the sham group, while in the tACS group the youngest participants with less years of education benefit more from the stimulation. These results emphasize the importance of further investigating and taking into account sex, age, and education as moderating factors in the development of individualized stimulation protocols. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03475446.

Teleconsultations for mental health: Recommendations from a Delphi panel.

Introduction: The use of teleconsultations for mental health has drastically increased since 2020 due to the Covid19 pandemic. In the present paper, we aimed to analyze the advantages and disadvantages of teleconsultations for mental health compared to face-to-face consultations, and to provide recommendations in this domain. Methods: The recommendations were gathered using a Delphi methodology. The expert panel (N = 21) included professionals from the health and ICT domains. They answered questions via two rounds of web surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with non-experts (N = 104). Results: Both the experts and the non-experts with teleconsultation experience reported a general satisfaction concerning teleconsultations. A SWOT analysis revealed several strengths and opportunities of teleconsultations for mental health, but also several weaknesses and threats. The experts provided a set of practical recommendations for the preparation and organization of teleconsultations for mental health. Discussion: Teleconsultations for mental health have the potential to allow access to care for patients in remote and isolated areas. Thus, their use will unlikely be discontinued after the end of the pandemic. In this context, we suggest that the collaboration among clinicians, researchers, and interface designers is crucial to improve usability and user experience for both clinicians and patients. The importance of teaching teleconsultation skills and informing the public on the features of teleconsultations (e.g., data privacy/security) is also highlighted.

The Hierarchy of Coupled Sleep Oscillations Reverses with Aging in Humans.

A well orchestrated coupling hierarchy of slow waves and spindles during slow-wave sleep supports memory consolidation. In old age, the duration of slow-wave sleep and the number of coupling events decrease. The coupling hierarchy deteriorates, predicting memory loss and brain atrophy. Here, we investigate the dynamics of this physiological change in slow wave-spindle coupling in a frontocentral electroencephalography position in a large sample (N = 340; 237 females, 103 males) spanning most of the human life span (age range, 15-83 years). We find that, instead of changing abruptly, spindles gradually shift from being driven by slow waves to driving slow waves with age, reversing the coupling hierarchy typically seen in younger brains. Reversal was stronger the lower the slow-wave frequency, and starts around midlife (age range, ∼40-48 years), with an established reversed hierarchy between 56 and 83 years of age. Notably, coupling strength remains unaffected by age. In older adults, deteriorating slow wave-spindle coupling, measured using the phase slope index (PSI) and the number of coupling events, is associated with blood plasma glial fibrillary acidic protein levels, a marker for astrocyte activation. Data-driven models suggest that decreased sleep time and higher age lead to fewer coupling events, paralleled by increased astrocyte activation. Counterintuitively, astrocyte activation is associated with a backshift of the coupling hierarchy (PSI) toward a "younger" status along with increased coupling occurrence and strength, potentially suggesting compensatory processes. As the changes in coupling hierarchy occur gradually starting at midlife, we suggest there exists a sizable window of opportunity for early interventions to counteract undesirable trajectories associated with neurodegeneration.SIGNIFICANCE STATEMENT Evidence accumulates that sleep disturbances and cognitive decline are bidirectionally and causally linked, forming a vicious cycle. Improving sleep quality could break this cycle. One marker for sleep quality is a clear hierarchical structure of sleep oscillations. Previous studies showed that sleep oscillations decouple in old age. Here, we show that, rather, the hierarchical structure gradually shifts across the human life span and reverses in old age, while coupling strength remains unchanged. This shift is associated with markers for astrocyte activation in old age. The shifting hierarchy resembles brain maturation, plateau, and wear processes. This study furthers our comprehension of this important neurophysiological process and its dynamic evolution across the human life span.

[Graduate medical education in old age psychiatry: a scoping literature review]. / Weiterbildungsdidaktik in der Alterspsychiatrie und -psychotherapie ­ Eine Literaturübersicht.

BACKGROUND: Gerontopsychiatry will become increasingly relevant as a discipline for primary care based on current demographic forecasts, destigmatization of mental illness and specific diagnostic and therapeutic developments. Hence, high quality graduate medical training in old age psychiatry is needed. Objectives The goal of this review was to summarize the literature on medical education relevant to residency training in old age psychiatry and to contrast the findings with international developments in competency-based medical education. MATERIALS AND METHODS: The authors used the scoping review method of Arksey and O'Malley. RESULTS: The initial search yielded 913 hits. After full text screening, 20 original articles were used for data extraction. The study content was summarized under three categories: trainee recruitment, length and structure of graduate training curricula in old age psychiatry, and learning goals and competencies in old age psychiatry training. Surveys and expert consensus were mostly used as study methods. High-quality clinical training experience with gerontopsychiatric patients and supervision of residents was an important factor for stimulating interest in old age psychiatry. Few studies provided evidence for educational benefit of digital learning and teaching formats and simulation training in old age psychiatry. Overall, there were no studies in old age psychiatry with explicit reference to concepts of competency-based graduate medical education. CONCLUSIONS: Clinical rotations and mentoring foster interest of clinical residents in the discipline of old age psychiatry. Systematically introducing clinical rotations in old age psychiatry in general psychiatry residency programs seems necessary to enable residents to gain relevant knowledge and skills. Educational research in old age psychiatry considering patient outcomes seems to be a meaningful next step.

Trainee doctors' preparedness for clinical work in geriatric psychiatry: A survey on 18 preliminary entrustable professional activities.

BACKGROUND: Research concerning transitions from one rotation to another during medical specialist training is scarce. This study examined trainee doctors' perceived preparedness for core clinical activities, trainee doctors' preparedness levels, and general perceptions of medical specialist training in geriatric psychiatry. METHOD: Swiss trainee doctors in geriatric psychiatry were surveyed about their perceived preparedness for 18 preliminary entrustable professional activities (EPAs), curricular support, and general perceptions of their medical specialist training. Closed questions were analysed using descriptive statistics, while open questions were subjected to content analysis. RESULTS: The participants comprised 48 trainee doctors (30.4% response rate) who differed in their educational experience (years of residency and specialism) and clinical subspecialisation goals. Trainee doctors felt adequately prepared for most EPAs but less prepared for some, including electroconvulsive therapy, psychotherapy, and treating older adults in the home environment or residential facilities. Despite the trainee doctors' diversity, they did not differ significantly in perceived preparedness for most EPAs. The most often offered suggestions for improving geriatric psychiatry training were intensified clinical supervision and a structured induction programme. CONCLUSION: Trainee doctors reported that they felt sufficiently prepared for most EPAs, regardless of their backgrounds and professional goals. However, several professional activities in geriatric psychiatry warrant further training. Our findings indicate the need for a higher intensity of clinical supervision (e.g. more direct observation and specific feedback), the introduction of structured induction programmes (e.g. orientation week), and specific teachings (e.g. on neurocognitive assessment).

[Qualitätsstandards in der Alterspsychiatrie]. / Standards de qualité en psychiatrie de la personne âgée.

Quality Standards in Old Age Psychiatry Abstract: Quality standards and regulations are becoming increasingly important and are promoted in the context of the permission to treat, to bill and via financial incentives. In this context, the regulatory frameworks focus to varying degrees on structural, process or outcome criteria. On behalf of the Swiss Society for Old Age Psychiatry and Psychotherapy (SGAP), we summarize the quality elements in this document and group the requirements derived from them based on setting (outpatient, intermediate, inpatient) and structural quality criteria (staffing ratio, infrastructure). There is a very extensive requirements matrix, and its implementation requires considerable efforts, not least because of the shortage of specialists and limited financial resources of psychiatric institutions and medical practices. The criteria of the requirements matrix must be further developed and anchored in a "competence-based training in old age psychiatry".

Résumé: Les normes et réglementations en matière de qualité prennent de plus en plus d'importance et sont encouragées dans le cadre de l'approbation des thérapeutiques, de la facturation et des incitations financières. Dans ce contexte, ces réglementations mettent l'accent, à des degrés divers, sur des critères de structure, de processus ou de résultats. Au nom de la Société Suisse de Psychiatrie et Psychothérapie de la Personne Âgée (SPPA) nous résumons dans ce document les éléments de qualité et regroupons les exigences qui en découlent en fonction du setting (ambulatoire, intermédiaire, stationnaire) et des critères de qualité structurelle (clé de répartition du personnel, infrastructure). Il existe une vaste matrice d'exigences dont la mise en œuvre requiert des efforts considérables, entre autres en raison de la pénurie de personnel qualifié et des ressources financières limitées des institutions et des cabinets médicaux. Les critères définis dans la matrice d'exigences devraient être développés et ancrés dans une «formation continue en psychiatrie de la personne âgée basée sur les compétences¼.

Adaptive data-driven selection of sequences of biological and cognitive markers in pre-clinical diagnosis of dementia.

Effective clinical decision procedures must balance multiple competing objectives such as time-to-decision, acquisition costs, and accuracy. We describe and evaluate POSEIDON, a data-driven method for PrOspective SEquentIal DiagnOsis with Neutral zones to individualize clinical classifications. We evaluated the framework with an application in which the algorithm sequentially proposes to include cognitive, imaging, or molecular markers if a sufficiently more accurate prognosis of clinical decline to manifest Alzheimer's disease is expected. Over a wide range of cost parameter data-driven tuning lead to quantitatively lower total cost compared to ad hoc fixed sets of measurements. The classification accuracy based on all longitudinal data from participants that was acquired over 4.8 years on average was 0.89. The sequential algorithm selected 14 percent of available measurements and concluded after an average follow-up time of 0.74 years at the expense of 0.05 lower accuracy. Sequential classifiers were competitive from a multi-objective perspective since they could dominate fixed sets of measurements by making fewer errors using less resources. Nevertheless, the trade-off of competing objectives depends on inherently subjective prescribed cost parameters. Thus, despite the effectiveness of the method, the implementation into consequential clinical applications will remain controversial and evolve around the choice of cost parameters.

Investigating Compensatory Brain Activity in Older Adults with Subjective Cognitive Decline.

BACKGROUND: Preclinical Alzheimer's disease (AD) is one possible cause of subjective cognitive decline (SCD). Normal task performance despite ongoing neurodegeneration is typically considered as neuronal compensation, which is reflected by greater neuronal activity. Compensatory brain activity has been observed in frontal as well as parietal regions in SCD, but data are scarce, especially outside the memory domain. OBJECTIVE: To investigate potential compensatory activity in SCD. Such compensatory activity is particularly expected in participants where blood-based biomarkers indicated amyloid positivity as this implies preclinical AD. METHODS: 52 participants with SCD (mean age: 71.00±5.70) underwent structural and functional neuroimaging (fMRI), targeting episodic memory and spatial abilities, and a neuropsychological assessment. The estimation of amyloid positivity was based on plasma amyloid-ß and phosphorylated tau (pTau181) measures. RESULTS: Our fMRI analyses of the spatial abilities task did not indicate compensation, with only three voxels exceeding an uncorrected threshold at p < 0.001. This finding was not replicated in a subset of 23 biomarker positive individuals. CONCLUSION: Our results do not provide conclusive evidence for compensatory brain activity in SCD. It is possible that neuronal compensation does not manifest at such an early stage as SCD. Alternatively, it is possible that our sample size was too small or that compensatory activity may be too heterogeneous to be detected by group-level statistics. Interventions based on the individual fMRI signal should therefore be explored.

Feasibility, efficacy, and functional relevance of automated auditory closed-loop suppression of slow-wave sleep in humans.

Slow-wave sleep (SWS) is a fundamental physiological process, and its modulation is of interest for basic science and clinical applications. However, automatised protocols for the suppression of SWS are lacking. We describe the development of a novel protocol for the automated detection (based on the whole head topography of frontal slow waves) and suppression of SWS (through closed-loop modulated randomised pulsed noise), and assessed the feasibility, efficacy and functional relevance compared to sham stimulation in 15 healthy young adults in a repeated-measure sleep laboratory study. Auditory compared to sham stimulation resulted in a highly significant reduction of SWS by 30% without affecting total sleep time. The reduction of SWS was associated with an increase in lighter non-rapid eye movement sleep and a shift of slow-wave activity towards the end of the night, indicative of a homeostatic response and functional relevance. Still, cumulative slow-wave activity across the night was significantly reduced by 23%. Undisturbed sleep led to an evening to morning reduction of wake electroencephalographic theta activity, thought to reflect synaptic downscaling during SWS, while suppression of SWS inhibited this dissipation. We provide evidence for the feasibility, efficacy, and functional relevance of a novel fully automated protocol for SWS suppression based on auditory closed-loop stimulation. Future work is needed to further test for functional relevance and potential clinical applications.

The promise of portable remote auditory stimulation tools to enhance slow-wave sleep and prevent cognitive decline.

Dementia is the seventh leading cause of mortality, and a major source of disability and dependency in older individuals globally. Cognitive decline (and, to a lesser extent, normal ageing) are associated with sleep fragmentation and loss of slow-wave sleep. Evidence suggests a bidirectional causal link between these losses. Phase-locked auditory stimulation has emerged as a promising non-invasive tool to enhance slow-wave sleep, potentially ameliorating cognitive decline. In laboratory settings, auditory stimulation is usually supervised by trained experts. Different algorithms (simple amplitude thresholds, topographic correlation, sine-wave fitting, phase-locked loop, and phase vocoder) are used to precisely target auditory stimulation to a desired phase of the slow wave. While all algorithms work well in younger adults, the altered sleep physiology of older adults and particularly those with neurodegenerative disorders requires a tailored approach that can adapt to older adults' fragmented sleep and reduced amplitudes of slow waves. Moreover, older adults might require a continuous intervention that is not feasible in laboratory settings. Recently, several auditory stimulation-capable portable devices ('Dreem®', 'SmartSleep®' and 'SleepLoop®') have been developed. We discuss these three devices regarding their potential as tools for science, and as clinical remote-intervention tools to combat cognitive decline. Currently, SleepLoop® shows the most promise for scientific research in older adults due to high transparency and customizability but is not commercially available. Studies evaluating down-stream effects on cognitive abilities, especially in patient populations, are required before a portable auditory stimulation device can be recommended as a clinical preventative remote-intervention tool.

Apathy in patients with Alzheimer's disease is a cost-driving factor.

BACKGROUND: Apathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers. METHODS: Included were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment. The Resource Utilization in Dementia (RUD) instrument assessed costs over a 1-month period prior to baseline. Cost predictors were determined via a least absolute shrinkage and selection operator (LASSO). RESULTS: On average, total monthly costs were €3070, of which €2711 accounted for caregivers' and €359 for patients' costs. An increase of one point in the Apathy Evaluation Scale resulted in a 4.1% increase in total costs. DISCUSSION: Apathy is a significant cost driving factor for total costs in mild to moderate DAT. Effective treatment of apathy might be associated with reduced overall costs in DAT.

Submillimeter T1 atlas for subject-specific abnormality detection at 7T.

PURPOSE: Studies at 3T have shown that T1 relaxometry enables characterization of brain tissues at the single-subject level by comparing individual physical properties to a normative atlas. In this work, an atlas of normative T1 values at 7T is introduced with 0.6 mm isotropic resolution and its clinical potential is explored in comparison to 3T. METHODS: T1 maps were acquired in two separate healthy cohorts scanned at 3T and 7T. Using transfer learning, a template-based brain segmentation algorithm was adapted to ultra-high field imaging data. After segmenting brain tissues, volumes were normalized into a common space, and an atlas of normative T1 values was established by modeling the T1 inter-subject variability. A method for single-subject comparisons restricted to white matter and subcortical structures was developed by computing Z-scores. The comparison was applied to eight patients scanned at both field strengths for proof of concept. RESULTS: The proposed method for morphometry delivered segmentation masks without statistically significant differences from those derived with the original pipeline at 3T and achieved accurate segmentation at 7T. The established normative atlas allowed characterizing tissue alterations in single-subject comparisons at 7T, and showed greater anatomical details compared with 3T results. CONCLUSION: A high-resolution quantitative atlas with an adapted pipeline was introduced and validated. Several case studies on different clinical conditions showed the feasibility, potential and limitations of high-resolution single-subject comparisons based on quantitative MRI atlases. This method in conjunction with 7T higher resolution broadens the range of potential applications of quantitative MRI in clinical practice.

The left prefrontal cortex determines relevance at encoding and governs episodic memory formation.

The role hemispheric lateralization in the prefrontal cortex plays for episodic memory formation in general, and for emotionally valenced information in particular, is debated. In a randomized, double-blind, and sham-controlled design, healthy young participants (n = 254) performed 2 runs of encoding to categorize the perceptual, semantic, or emotionally valenced (positive or negative) features of words followed by a free recall and a recognition task. To resolve competing hypotheses about the contribution of each hemisphere, we modulated left or right dorsolateral prefrontal cortex (DLPFC) activity using transcranial direct current stimulation during encoding (1 mA, 20 min). With stimulation of the left DLPFC, but not the right DLPFC, encoding and free recall performance improved particularly for words that were processed semantically. In addition, enhancing left DLPFC activity increased memory formation for positive content while reducing that for negative content. In contrast, promoting right DLPFC activity increased memory formation for negative content. The left DLPFC assesses semantic properties of new memory content at encoding and thus influences how successful new episodic memories are established. Hemispheric laterlization-more active left DLPFC and less active right DLPFC-at the encoding stage shifts the formation of memory traces in favor of positively valenced content.

[Measures restricting freedom in the geriatric psychiatry].

INTRODUCTION: Measures restricting freedom include physical restraints restricting movement and treatment without consent according to the Swiss Civil Code. Patients incapable of consenting to treatments and other measures of care and who are somatically multimorbid in addition to their mental illness are frequently encountered in the geriatric psychiatry inpatient setting. In this group of patients, physical restraints are repeatedly used to prevent falling and to quarantine patients due to infectious diseases. Frequently, treatment is conducted with the apparent agreement of the patient but which are to be recorded as measures restricting freedom due to the inability to give informed consent. The National Association for Quality Development in Hospitals and Clinics (ANQ) has introduced geriatric psychiatry as a separate department category; this differentiation should also be seen as an opportunity and invitation to take a differentiated look at measures restricting freedom in geriatric psychiatry.

Acoustic stimulation during sleep predicts long-lasting increases in memory performance and beneficial amyloid response in older adults.

BACKGROUND: Sleep and neurodegeneration are assumed to be locked in a bi-directional vicious cycle. Improving sleep could break this cycle and help to prevent neurodegeneration. We tested multi-night phase-locked acoustic stimulation (PLAS) during slow wave sleep (SWS) as a non-invasive method to improve SWS, memory performance and plasma amyloid levels. METHODS: 32 healthy older adults (agemean: 68.9) completed a between-subject sham-controlled three-night intervention, preceded by a sham-PLAS baseline night. RESULTS: PLAS induced increases in sleep-associated spectral-power bands as well as a 24% increase in slow wave-coupled spindles, known to support memory consolidation. There was no significant group-difference in memory performance or amyloid-beta between the intervention and control group. However, the magnitude of PLAS-induced physiological responses were associated with memory performance up to 3 months post intervention and beneficial changes in plasma amyloid. Results were exclusive to the intervention group. DISCUSSION: Multi-night PLAS is associated with long-lasting benefits in memory and metabolite clearance in older adults, rendering PLAS a promising tool to build upon and develop long-term protocols for the prevention of cognitive decline.