Abstract INTRODUCTION Physical activity is a promising non‐pharmacological approach to support brain health. Although prior studies suggest cognitive benefits, it remains unclear how exercise alters brain structure and connectivity on the Alzheimer's disease (AD) continuum and whether such neural changes translate to functional improvements. This study investigated whether a multicomponent physical‐activity program induced measurable brain changes across the AD continuum. METHODS In the Dementia‐MOVE (Multi‐Objective Validation of Exercise) randomized‐controlled trial, 46 participants with early AD were allocated to either a 6‐month multicomponent physical activity intervention (n = 25) or a psychoeducation program (n = 21). Magnetic resonance imaging (MRI) and clinical assessments were conducted at baseline (T1), after intervention (T3), and 18 months (T4) after T1. Structural MRI was conducted at all timepoints; resting‐state functional MRI was conducted at T1 and T3. Longitudinal analyses evaluated changes in brain volume and functional connectivity and their correlations with cognitive, physical, and fitness profiles. RESULTS Structural analyses revealed long‐term reductions in gray and white matter volumes and ventricular expansion in both groups, with no significant group‐by‐time interaction. There was no significant change on brain structure right after intervention at T3. In contrast, functional connectivity increased after an intervention in the physical activity group, particularly in frontal, limbic, and cerebellar regions. Between‐group comparisons showed higher connectivity in the intervention group at T3 with no difference in connectivity between both groups at T1. Correlation analyses demonstrated stronger and more widespread association patterns between brain metrics, especially on the functional level, and cognitive, fitness, and activity measures in the intervention group at follow‐up. DISCUSSION These findings suggest that structured physical activity induces functional reorganization and strengthens brain–behavior coupling in early AD, while structural differences between groups stabilize first and decline after cessation of the intervention. Multimodal imaging may offer a sensitive approach to detecting early neuroplasticity responses, and sustained engagement may therefore be necessary to maintain effects.

INTRODUCTION:Sleep is a modifiable risk factor in Alzheimer's disease (AD), but its relationship to medial temporal lobe (MTL) subfields and responsiveness to lifestyle interventions remain unclear. METHODS:In the Dementia-Multi-Objective Validation of Exercise (MOVE) study, 46 individuals on the AD continuum were randomized to 6 months of multimodal exercise (n = 25) or psychoeducation (n = 21) and followed for 18 months (T1-T4). Clinical and cognitive testing, sleep/activity measures (PSQI, diaries, wearables), high-resolution T1, and resting-state functional magnetic resonance imaging scans were acquired. Hippocampal and amygdala subfield volumes and hippocampus-amygdala connectivity were analyzed longitudinally. RESULTS:After the 6-month intervention, the intervention group showed increased hippocampus-amygdala connectivity and attenuated subfield atrophy. One year later, both groups progressed in cognitive decline and hippocampal atrophy. Hippocampal and amygdalar volumes and connectivity were associated with sleep parameters as well as activity and cognitive parameters. DISCUSSION:Exercise was associated with short-term MTL preservation and network reorganization linked to sleep and activity, supporting continuous physical activity for lasting benefits.

Physical exercise presents a viable low-cost, low-risk, individual, and widely available non-pharmacological treatment candidate in cognitive decline such as in Alzheimer’s disease (AD). There are even indications that it can reduce the risk of developing dementia in the first place (Livingston et al. , The Lancet, 2020). However, the impact of physical activity and fitness on the multimodal facets of AD, encompassing brain function, cognition and metabolism is still poorly understood. In the Dementia-MOVE pilot trial ( M ulti- O bjective V alidation of E xercise), 46 patients diagnosed with Alzheimer’s disease were initially included, randomized to either an intervention arm comprising a 6 months-supervised sports program or a control condition with a psychoeducational program at the RWTH Aachen University Hospital. Participants underwent a comprehensive multimodal assessment of AD relevant parameters, including multimodal MRI, fitness and activity, neuropsychological assessments, blood examinations and the assessments of neuropsychiatric symptoms (Haeger et al. , Alzheimers’s & Dementia TRCI, 2020). In the intervention group, cardiorespiratory fitness change, i.e. ΔVO 2 max, showed a positive association with changes in the Montreal Cognitive Assessment (MoCA), in the executive functions score, and in volumes of the temporal lobe. It also showed a negative correlation with baseline cognitive levels (see also Figure 1 on the multiple regression analysis). High physical activity levels were associated with improved quality of life in the overall sample. In functional MRI using resting state and graph theory ( n = 20 subjects), we found prediction by ΔVO 2 max for changes on the degree, betweenness, triangles, transitivity, hubness, closeness and Katz centrality, with the last showing the most effects in regions in the temporal lobe. Metabolic MRI comprising 23 Na-MRI and 31 P-MRS pointed to possible associations of VO 2 max and/or group attribution with changes in brain sodium concentrations/cerebral metabolites. We show that cardiorespiratory fitness and physical activity examined during an intervention with physical activity can have an impact on different aspects of AD, from cognition, to structural, functional, and metabolic brain alterations. Our results suggest that even patients who are more severely affected by the disease could benefit from interventions in these domains.

Background Physical activity and fitness are major targets in Alzheimer's disease (AD) preventive research. However, current research is heterogeneous and often disregards the relationship between these parameters and disease outcomes. Objective To assess the effects of physical activity and fitness on AD within the context of a multicomponent sports intervention. Methods 46 participants with early-stage AD (mean age 70 ± 7 years, 18 women, mean Montreal Cognitive Assessment (MoCA) score 19±5) were included in a six-month randomized controlled trial (Dementia-MOVE), participating in either a multicomponent sports intervention or a control condition with a psychoeducational program. The modulating effect of fitness and physical activity changes on AD outcome parameters such as cognition, function and cerebral brain structure from 3T-MRI were examined using multiple linear regression analyses. Results An increase in VO2max was associated with assignment to the intervention group ( p = 0.016), lower baseline fitness ( p = 0.001), and an increased rate of physical activity ( p = 0.046). Only in the intervention group, ΔVO2max had a beneficial modulating effect on the MoCA score ( p = 0.039), the executive functions ( p = 0.017) and regional brain volumes of the temporal lobe, e.g., the hippocampus ( p = 0.044). High daily step count was associated with preserved executive functions ( p = 0.001), and caregivers’ quality of life ( p ≤ 0.001) in the overall sample. Conclusions Our results confirm that multicomponent exercise improves cardiorespiratory fitness in AD, which is associated with advantageous developments in cognitive performance and preservation of brain structure. These findings suggest that especially patients with comparably worse cognition and fitness benefit and should be encouraged for activity engagement.

OBJECTIVE:The aim of this study was to compare image quality features and lesion characteristics between a faster deep learning (DL) reconstructed T2-weighted (T2-w) fast spin-echo (FSE) Dixon sequence with super-resolution (T2DL) and a conventional T2-w FSE Dixon sequence (T2STD) for breast magnetic resonance imaging (MRI). MATERIALS AND METHODS:This prospective study was conducted between November 2022 and April 2023 using a 3T scanner. Both T2DL and T2STD sequences were acquired for each patient. Quantitative analysis was based on region-of-interest (ROI) measurements of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Qualitative analysis was performed independently by two radiologists using Likert scales to evaluate various image quality features, morphology, and diagnostic confidence for cysts and breast cancers. Reader preference between T2DL and T2STD was assessed via side-by-side comparison, and inter-reader reliability was also analyzed. RESULTS:Total of 151 women were enrolled, with 140 women (mean age: 52 ± 14 years; 85 cysts and 31 breast cancers) included in the final analysis. The acquisition time was 110 s ± 0 for T2DL compared to 266 s ± 0 for T2STD. SNR and CNR were significantly higher in T2DL (P < 0.001). T2DL was associated with higher image quality scores, reduced noise, and fewer artifacts (P < 0.001). All evaluated anatomical regions (breast and axilla), breast implants, and bone margins were rated higher in T2DL (P ≤ 0.008), except for bone marrow, which scored higher in T2STD (P < 0.001). Scores for conspicuity, sharpness/margins, and microstructure of cysts and breast cancers were higher in T2DL (P ≤ 0.002). Diagnostic confidence for cysts was improved with T2DL (P < 0.001). Readers significantly preferred T2DL over T2STD in side-by-side comparisons (P < 0.001). CONCLUSION:T2DL effectively corrected for SNR loss caused by accelerated image acquisition and provided a 58% reduction in acquisition time compared to T2STD. This led to fewer artifacts and improved overall image quality. Thus, T2DL is feasible and has the potential to replace conventional T2-w sequences for breast MRI examinations.

Phosphorus magnetic resonance spectroscopy (31P-MRS) is applied for non-invasive studies of neuroenergetic metabolism in neurodegenerative diseases. However, the findings are inconsistent and have not yet been tested in meta-analyses. To address this gap, we performed a systematic review of 29 studies and conducted meta-analyses for 9 studies on Alzheimer’s disease (AD, n=140 patients), 9 studies on Parkinson’s disease (PD, n=183 patients), 3 studies on Progressive Supranuclear Palsy (PSP, n=42 patients), and 2 studies on Multiple System Atrophy (MSA, n=24 patients). Compared to controls, AD patients had a higher ratio of phosphomonoesters/phosphodiesters (PME/PDE) in the frontal lobe (MD=0.049, p=0.0003); PD patients showed decreases in PME/PDE in the putamen (MD=-0.050, p=0.023) and adenosine triphosphate/inorganic phosphate (ATP/Pi) in the midbrain (MD=-0.274, p=0.002); PSP patients presented increased phosphocreatine (PCr)/Pi in the basal ganglia (MD=0.556, p=0.030) and adenosine diphosphate (ADP)/Pi in the occipital lobe (MD=0.005, p=0.009); no significant effects were observed in MSA. Here, our review underlines the importance of 31P-MRS in the characterization of distinct neuroenergetic changes and its potential to improve the diagnosis and follow-up of neurodegenerative diseases.

Introduction: Alzheimer disease (AD) is a progressive neurodegenerative disease that accounts for 60% of dementia cases worldwide. Despite the lack of concrete information about the prevalence of dysphagia among AD patients, it still significantly impairs their quality of life (QoL). That outcome necessitates more investigations to understand the pathophysiology of this condition and how to manage it. In this study, we examined if AD-associated changes in pharyngeal and tongue muscles could explain dysphagia. Methods: Fourteen adult male rats were allocated into 2 groups: Group I (control) received distilled water orally, group II (AD) received aluminum chloride (AlCl3) (200 mg/kg, per os) and D-galactose (60 mg/kg, subcutaneous) daily for 45 days. Biochemical parameters were conducted, including amyloid beta-peptide (A(3), histopathological investigation of the hippocampus, tongue, and pharynx, and immune-histochemical expression of brain glial fibrillar acidic protein (GFAP). Results: Our AD model showed marked cognitive impairment, hippocampal oxidative stress, and increased brainA(3 expression (P=0.0003) compared to controls. Dysphagiawas confirmed by loss of body weight (P=0.0077) and decreased eating and drinking patterns by 25%-35% in AD versus the control group. Histopathological, immune-histochemical, and biochemical evidence, including increased levels of pharyngeal A(3 (P=0.0017), were detected in AD rats' tongue and pharyngeal muscles. Conclusion: Dysphagia inAD can result not only centrally but also due to local involvement of the tongue and pharynx. Further translational studies linking dysphagia to AD pathology will be needed.

AbstractObjectiveCommunication skills can deteriorate in neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD); however, their clinical assessment and treatment in patient care can be challenging. In the present study, we aimed to quantify the distinctive communication resources and barriers reported by patients and their relatives in AD and FTD and associated these communicative characteristics with clinical parameters, such as the degree of cognitive impairment and atrophy in language‐associated brain areas.MethodsWe assessed self‐reported communication barriers and resources in 33 individuals with AD and FTD through an interview on daily‐life communication, using the Aachener KOMPASS questionnaire. We correlated reported communication barriers and resources with atrophy from high‐resolution 3T brain magnetic resonance imaging, neuropsychological assessment, and neurodegenerative markers from cerebrospinal fluid.ResultsCommunicative impairment was higher in FTD compared to AD. Increased reported communication barriers in our whole sample were associated with the atrophy rate in the left middle temporal lobe, a critical site within the neuronal language network, and with depressive symptoms as well as the semantic word fluency from neuropsychological assessment. The best model for prediction of communicative impairment included the diagnosis (AD or FTD), semantic word fluency, and depressive symptoms.ConclusionsOur study demonstrates that communication barriers and resources can be successfully assessed via a structured interview based on self‐report and report of patients’ relatives in practice and are reflected in neuroimaging specific for AD and FTD as well as in further clinical parameters specific for these neurodegenerative diseases. This can potentially open new treatment options for clinical practice and patient care.

Introduction:Assessment methods for physical activity and fitness are of upmost importance due to the possible beneficial effect of physical conditioning on neurodegenerative diseases. The implementation of these methods can be challenging when examining elderly or cognitively impaired participants. In the presented study, we compared three different assessment methods for physical activity from the Dementia-MOVE trial, a 6-months intervention study on physical activity in Alzheimer's disease. The aim was to determine the comparability of physical activity assessments in elderly participants with cognitive impairment due to Alzheimer's disease.Material or methods:38 participants (mean age 70 ± 7 years) with early-stage Alzheimer's disease (mean MoCA 18.84 ± 4.87) were assessed with (1) fitness trackers for an average of 12 (± 6) days, (2) a written diary on daily activities and (3) a questionnaire on physical activity at three intervention timepoints. For comparison purposes, we present a transformation and harmonization method of the physical assessment output parameters: Metabolic equivalent of task (MET) scores, activity intensity minutes, calorie expenditure and moderate-to-vigorous physical activity (MVPA) scores were derived from all three modalities. The resulting parameters were compared for absolute differences, correlation, and their influence by possible mediating factors such as cognitive state and markers from cerebrospinal fluid.Results:Participants showed high acceptance and compliance to all three assessment methods. MET scores and MVPA from fitness trackers and diaries showed high overlap, whilst results from the questionnaire suggest that participants tended to overestimate their physical activity in the long-term retrospective assessment. All activity parameters were independent of the tested Alzheimer's disease parameters, showing that not only fitness trackers, but also diaries can be successfully applied for physical activity assessment in a sample affected by early-stage Alzheimer's disease.Discussion:Our results show that fitness trackers and physical activity diaries have the highest robustness, leading to a highly comparable estimation of physical activity in people with Alzheimer's disease. As assessed parameters, it is recommendable to focus on MET, MVPA and on accelerometric sensor data such as step count, and less on activity calories and different activity intensities which are dependent on different variables and point to a lower reliability.

[18F]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is applied to delineate cerebral glucose metabolic patterns in Alzheimer’s disease (AD). Sodium MR imaging ( 23 Na-MRI) can reveal alterations in tissue sodium concentration (TSC) in the brain, potentially reflecting mitochondrial dysfunction and impaired cellular energy state. This initial study aims at investigating disease-specific topographical associations between glucose metabolism assessed via FDG-PET and regional TSC from 23 Na-MRI, thus improving our understanding of neuroenergetics alteration in AD. 20 patients with a biological biomarker-based diagnosis of prodromal/mild AD (mean age 68±7.5; 8 females; CDR 0.75±0.57, MMSE 23.9±4.2) received an FDG-PET, 23 Na-MRI and 1 H-MRI at 3T magnetic field (Siemens Prisma). A variable flip angle method was used to obtain TSC maps (Coste et al., 2019). To control for inter-individual differences, FDG-PET and TSC images were intensity-normalized to the brainstem to create normalized glucose metabolism (nFDG) and normalized TSC maps (nTSC) (de Souza et al., 2011; Nugent et al., 2020), respectively. The Hammersmith and VolBrain Segmentation atlases were applied for region-of-interest analysis and to create correlation matrices between nFDG, nTSC and normalized local brain volume. Regional nTSC negatively correlated with nFDG in AD patients mainly in temporal lobe structures and superior frontal gyri, indicating that decreased glucose metabolism was associated with increased TSC and vice versa. As expected, regional volume was positively correlated with nFDG in regions of the temporal lobe. When performing partial correlation controlling for volume, negative correlation clusters between nTSC and nFDG remained significant for superior frontal gyri and the anterior temporal lobes (Figure 1). For the first time, the association between local glucose consumption rates and sodium concentrations were investigated in AD using combined FDG-PET and 23 Na-MRI at 3T. Consistently to our recent findings of increased TSC in AD patients (Haeger et al., 2021), the negative correlations between nTSC and nFDG values in temporal and frontal brain regions, are confirming the interplay between reduced energy metabolism and sodium increase in AD, the exact nature of which remains to be determined. References: Coste […]. Magnetic Resonance Imaging 2019. Haeger […]. Alzheimer’s & Dementia 2021. Nugent […]. Scientific Reports 2020. de Souza […]. Brain 2011.

L'imagerie RMN du sodium (23Na) a démontrée à travers plusieurs études sa pertinence en tant que biomarqueur de viabilité cellulaire en particulier dans les maladies d'Alzheimer[1] ou la sclérose en plaques[2]. Les études actuelles utilisent des séquences à temps d'écho ultra-court combinées à des trajectoires déterministes non-Cartésiennes à travers l'espace de Fourier. Néanmoins, les temps d'acquisition restent long, même à très haut champ magnétique, en raison de la sensibilité intrinsèque et des concentrations tissulaires modérées du sodium. Bien que plus efficaces que les trajectoires Cartésiennes, les trajectoires non-Cartésiennes déterministes telles que TPI[3] n'exploitent pas au mieux la parcimonie de l'espace de Fourier en raison de leurs motifs géométriques. Par conséquent, nous avons proposé d'implémenter et évaluer une approche stochastique dénommée SPARKLING[4] (Fig. 1) dans le contexte de l'IRM 23Na cérébrale sous-échantillonnée. Guidé par une étude théorique basée sur un outil de simulation dédié, nous avons identifié des régimes favorables (en terme de signal et de résolution) exploitant la parcimonie des données IRM et ainsi d'accélérer (facteur d'accélération - FA = 8,32,64 et 128) l'acquisition tout en préservant les détails anatomiques et l'exactitude des concentrations en sodium calibrée à l'aide de 4 références externes[1]. Nous avons validé in vivo l'approche SPARKLING dans un de ces scénarios chez le volontaire sain (n=5 ; 7T Terra, Siemens Healthineers ; antenne 23Na 32 canaux, Rapid Biomedical), observant en particulier une qualité d'image similaire avec SPARKLING (Fig. 2: FA=32 ; TA= 5 min 38 s) comparé à celle d'acquisitions TPI plus longues (FA=8 ; TA= 22 min 34 s) avec un impact négligeable sur la quantification du sodium cérébral. A l'aide de SPARKLING, nous pouvons acquérir dans des conditions favorables des cartes cérébrales en sodium en un temps compatible avec les contraintes de la recherche clinique.

In patients with Friedreich ataxia, structural MRI is typically used to detect abnormalities primarily in the brainstem, cerebellum, and spinal cord. The aim of the present study was to additionally investigate possible metabolic changes in Friedreich ataxia using in vivo sodium MRI that may precede macroanatomical alterations, and to explore potential associations with clinical parameters of disease progression. Tissue sodium concentration across the whole brain was estimated from sodium MRI maps acquired at 3 T and compared between 24 patients with Friedreich ataxia (21–57 years old, 13 females) and 23 controls (21–60 years old, 12 females). Tensor-based morphometry was used to assess volumetric changes. Total sodium concentrations and volumetric data in brainstem and cerebellum were correlated with clinical parameters, such as severity of ataxia, activity of daily living and disability stage, age, age at onset, and disease duration. Compared to controls, patients showed reduced brain volume in the right cerebellar lobules I-V (difference in means: −0.039% of total intracranial volume [TICV]; Cohen's d = 0.83), cerebellar white matter (WM) (-0.105%TICV; d = 1.16), and brainstem (-0.167%TICV; d = 1.22), including pons (-0.102%TICV; d = 1.00), medulla (-0.036%TICV; d = 1.72), and midbrain (-0.028%TICV; d = 1.05). Increased sodium concentration was additionally detected in the total cerebellum (difference in means: 2.865 mmol; d = 0.68), and in several subregions with highest effect sizes in left (5.284 mmol; d = 1.01) and right cerebellar lobules I-V (5.456 mmol; d = 1.00), followed by increases in the vermis (4.261 mmol; d = 0.72), and in left (2.988 mmol; d = 0.67) and right lobules VI-VII (2.816 mmol; d = 0.68). In addition, sodium increases were also detected in all brainstem areas (3.807 mmol; d = 0.71 to 5.42 mmol; d = 1.19). After controlling for age, elevated total sodium concentrations in right cerebellar lobules IV were associated with younger age at onset (r = -0.43) and accordingly with longer disease duration in patients (r = 0.43). Our findings support the potential of in vivo sodium MRI to detect metabolic changes of increased total sodium concentration in the cerebellum and brainstem, the key regions in Friedreich ataxia. In addition to structural changes, sodium changes were present in cerebellar hemispheres and vermis without concomitant significant atrophy. Given the association with age at disease onset or disease duration, metabolic changes should be further investigated longitudinally and in larger cohorts of early disease stages to determine the usefulness of sodium MRI as a biomarker for early neuropathological changes in Friedreich ataxia and efficacy measure for future clinical trials.

Der 51-jährige Patient wurde uns konsiliarisch aus der Klinik für Unfallchirurgie vorgestellt.

INTRODUCTION:Application of MRI in clinical routine mainly addresses structural alterations. However, pathological changes at a cellular level are expected to precede the occurrence of brain atrophy clusters and of clinical symptoms. In this context, 23Na-MRI examines sodium changes in the brain as a potential metabolic parameter. Recently, we have shown that 23Na-MRI at ultra-high-field (7 T) was able to detect increased tissue sodium concentration (TSC) in Alzheimer's disease (AD). In this work, we aimed at assessing AD-pathology with 23Na-MRI in a larger cohort and on a clinical 3T MR scanner. METHODS:We used a multimodal MRI protocol on 52 prodromal to mild AD patients and 34 cognitively healthy control subjects on a clinical 3T MR scanner. We examined the TSC, brain volume, and cortical thickness in association with clinical parameters. We further compared TSC with intra-individual normalized TSC for the reduction of inter-individual TSC variability resulting from physiological as well as experimental conditions. Normalized TSC maps were created by normalizing each voxel to the mean TSC inside the brain stem. RESULTS:We found increased normalized TSC in the AD cohort compared to elderly control subjects both on global as well as on a region-of-interest-based level. We further confirmed a significant association of local brain volume as well as age with TSC. TSC increase in the left temporal lobe was further associated with the cognitive state, evaluated via the Montreal cognitive assessment (MoCA) screening test. An increase of normalized TSC depending on disease stage reflected by the Clinical Dementia Rating (CDR) was found in our AD patients in temporal lobe regions. In comparison to classical brain volume and cortical thickness assessments, normalized TSC had a higher discriminative power between controls and prodromal AD patients in several regions of the temporal lobe. DISCUSSION:We confirm the feasibility of 23Na-MRI at 3T and report an increase of TSC in AD in several regions of the brain, particularly in brain regions of the temporal lobe. Furthermore, to reduce inter-subject variability caused by physiological factors such as circadian rhythms and experimental conditions, we introduced normalized TSC maps. This showed a higher discriminative potential between different clinical groups in comparison to the classical TSC analysis. In conclusion, 23Na-MRI represents a potential translational imaging marker applicable e.g.for diagnostics and the assessment of intervention outcomes in AD even under clinically available field strengths such as 3T. Implication of 23Na-MRI in association with other metabolic imaging marker needs to be further elucidated.

Der 51-jahrige Patient wurde uns konsiliarisch aus der Klinik fur Unfallchirurgie vorgestellt.

Rationale: Face expertise is a pivotal social skill. Developmental prosopagnosia (DP), i.e., the inability to recognize faces without a history of brain damage, affects about 2% of the general population, and is a renowned model system of the face-processing network. Within this network, the right Fusiform Face Area (FFA), is particularly involved in face identity processing and may therefore be a key element in DP. Neural representations within the FFA have been examined with Representational Similarity Analysis (RSA), a data-analytical framework in which multi-unit measures of brain activity are assessed with correlation analysis. Objectives: Our study intended to scrutinize modifications of FFA-activation during face encoding and maintenance based on RSA. Methods: Thirteen participants with DP (23–70 years) and 12 healthy control subjects (19–62 years) participated in a functional MRI study, including morphological MRI, a functional FFA-localizer and a modified Sternberg paradigm probing face memory encoding and maintenance. Memory maintenance of one, two, or four faces represented low, medium, and high memory load. We examined conventional activation differences in response to working memory load and applied RSA to compute individual correlation-matrices on the voxel level. Group correlation-matrices were compared via Donsker’s random walk analysis. Results: On the functional level, increased memory load entailed both a higher absolute FFA-activation level and a higher degree of correlation between activated voxels. Both aspects were deficient in DP. Interestingly, control participants showed a homogeneous degree of correlation for successful trials during the experiment. In DP-participants, correlation levels between FFA-voxels were significantly lower and were less sustained during the experiment. In behavioral terms, DP-participants performed poorer and had longer reaction times in relation to DP-severity. Furthermore, correlation levels were negatively correlated with reaction times for the most demanding high load condition. Conclusion: We suggest that participants with DP fail to generate robust and maintained neural representations in the FFA during face encoding and maintenance, in line with poorer task performance and prolonged reaction times. In DP, alterations of neural coding in the FFA might therefore explain curtailing in working memory and contribute to impaired long-term memory and mental imagery.

INTRODUCTION Complex drug management is a common challenge in the treatment of geriatric patients. Pandemic scenarios, such as the current one (COVID-19), call for a reduction of face-to-face meetings, especially for elderly patients. Therefore, the aim of the present study was to compare the innovative concept of applying telemedical assessment to geriatric patients in the emergency department (ED) with ED standard treatment. The therapeutic recommendations regarding drug management from the two assessments were compared. A special focus was the use of potentially inadequate drugs (PIMs) for geriatric patients according to the “Fit for the Aged” (FORTA) classification. METHODS 50 patients (40% female) aged ≥70 years and assessed with an Identification of Seniors at Risk Score (ISAR score) of ≥2 admitted to the ED were prospectively enrolled in this study between November 2017 and February 2018. In addition to the standard treatment in the ED, co-evaluation via video transmission was independently carried out by a board-certified geriatrician. Drug recommendations by ED physicians (A) and the geriatrician (B) were compared. RESULTS There was a significantly higher frequency of recommendations regarding changes to preexisting medication (p <0.001, n = 50) via geriatric telemedicine in comparison with standard ED treatment. The geriatrician intervened significantly more often than the ED physicians: discontinuation of a drug, p <0.001; start of a new drug, p = 0.004; dose change of a drug, p = 0.001; n = 50). Based on the additional therapy recommendations of the geriatrician, the amount of medication taken by the patient was significantly reduced compared with standard ED treatment (ED assessment t(49) = 0.622 vs geriatrician’s assessment t(49) = 4.165; p <0.001; n = 50). Additionally, the number of PIMs was significantly reduced compared with standard medical treatment (p <0.001). The geriatrician changed 53.9% of the drugs (35/65) whereas the ED physicians changed only 12.3% (8/65). Recommendations for immediate drug therapy, however, were made more frequently by ED physicians (p <0.039, n = 50). DISCUSSION An early assessment of elderly emergency patients by a geriatrician had a significant impact on the number of drug interventions in the ED. The number of PIMs could be significantly reduced. Whether this also has a positive effect on the further inpatient course needs to be investigated in further prospective studies. The study was retrospectively registered at ClinicalTrials.gov (NCT04148027).

The pathophysiological processes underlying the development and progression of Alzheimer's disease (AD) on the neuronal level are still unclear. Previous research has hinted at metabolic energy deficits and altered sodium homeostasis with impaired neuronal function as a potential metabolic marker relevant for neurotransmission in AD. Using sodium (23 Na) magnetic resonance (MR) imaging on an ultra-high-field 7 Tesla MR scanner, we found increased cerebral tissue sodium concentration (TSC) in 17 biomarker-defined AD patients compared to 22 age-matched control subjects in vivo. TSC was highly discriminative between controls and early AD stages and was predictive for cognitive state, and associated with regional tau load assessed with flortaucipir-positron emission tomography as a possible mediator of TSC-associated neurodegeneration. TSC could therefore serve as a non-invasive, stage-dependent, metabolic imaging marker. Setting a focus on cellular metabolism and potentially disturbed interneuronal communication due to energy-dependent altered cell homeostasis could hamper progressive cognitive decline by targeting these processes in future interventions.

BACKGROUND:Physical activity has shown a positive impact on aging and neurodegeneration and represents a possible treatment option in cognitive decline. However, its underlying mechanisms and influences on brain pathology remain unclear. Dementia-MOVE (Multi-Objective Validation of Exercise) is a randomized-controlled pilot trial, including 50 patients with amnestic cognitive impairment associated with Alzheimer's pathology, aiming to analyze the effect of physical activity and fitness on disease progression.METHODS:Dementia-MOVE is divided into two arms, of either an intervention comprising physical activity, for at least twice a week, combined with a psychoeducational program, or a sole psychoeducational program. Physical activity intervention includes a supervised and unsupervised multimodal concept combining resistance, endurance, coordinative, and aerobic training. The primary outcome is the change of brain metabolism due to physical interventional treatment. Besides metabolic magnetic resonance imaging (MRI) including sodium and phosphorus imaging, resting state functional MRI, T1-, T2-weighted and fluid-attenuated inversion recovery (FLAIR), as well as diffusion-weighted imaging (DWI) of the brain and whole-body fat MRI are performed before and after intervention, and will be compared in their sensitivity for the detection of intervention effects. We further assess cognitive performance, neuropsychiatric symptoms, quality of life, fitness, and sleep via questionnaires/interviews and/or fitness trackers, as well as microbiome, under the aspect of Alzheimer's pathology.DISCUSSION:The aim of Dementia-MOVE is to investigate the effect of a multimodal exercise program on Alzheimer's pathology under different aspects of the disease. In this context, one of the main aims is the comparison of different MRI methods regarding their responsiveness for the detection of alterations induced by physical activity. As an underlying goal, new treatment and diagnostic options, as well as the exploration of fitness effects on brain structure and metabolism within a whole-body perspective of Alzheimer's disease are envisaged.