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.

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.

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.

Value-based motivational strategies combined with technology to encourage a lifestyle that helps to prevent dementia.

Lifestyles aimed at reducing dementia risk typically combine physical and cognitive training, nutritional adaptations, and, potentially, an augmentation in social interactions. Interventions at the population level are essential but should be complemented by individual efforts. For efficacy, lasting changes to an individual's lifestyle are needed, necessitating robust motivation and volition. Acting in accordance with one's values is assumed to be rewarding, leading to improved motivation and volition, and produces stable behaviour-outcome relationships. To this end, future preventive endeavours might first evaluate an individual's extant lifestyle, preferences, and values, including considerations of age-related changes to ensure these values remain a motivational source. Digital technology can support lifestyle goals and be targeted to support an individual's values. A digital platform could implement situation-specific, sensing-based feedback to alert users to a target situation (eg, opportunity for exercise) coupled with (smartphone-based) feedback on the extent of accomplished behavioural change to support individually set goals and facilitate their adjustment depending on whether these goals are achieved. This use of the motivational impetus of values, coupled with interpersonal techniques, such as motivational interviewing and SMART goal setting, in combination with sensor technology and just-in-time adaptive interventions, is assumed to hold high potential for dementia prevention.

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).

Antidepressants for treating depression among older adults with dementia: A systematic review and meta-analysis.

BACKGROUND: Depression and dementia represent significant health challenges in older adults. Despite guidelines recommending antidepressants, their efficacy in depressed patients with dementia remains undetermined. OBJECTIVE: This review, in following a living systematic review approach, primarily aims to determine the effect of any-type antidepressant on the level of depressive symptoms in older adults with dementia and secondly if there is an effect of any-type antidepressants on cognitive state, quality of life, and functionality in the old-age population with dementia. METHODS: Systematic review and meta-analysis of RCTs from Medline, Embase, and Cochrane Register. Participants were ≥65 years, with both depression and any type of dementia. Certainty-of-Evidence was assessed through the Cochrane Risk-of-Bias tool and GRADE. Analysis involved standardized mean difference, with 95 % confidence-intervals (CIs). FINDINGS: Of the 27,771 screened articles, 8 studies (617 participants), treated with SSRI, SSNRI, atypical, and tricyclic antidepressants were retained for quantitative synthesis. No evidence for an effect was found (SMD -0.10 [-0.26, 0.07]), nor when subgrouped based on depression severity or dementia level, nor for secondary outcomes. INTERPRETATION: This review did not find evidence of a clinical effect of antidepressants for treating depression in older adults with dementia. Methodological challenges might contribute to this finding.

[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.

[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.