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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. [ABSTRACT FROM AUTHOR]

Objective: Communication 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. Methods: We 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. Results: Communicative 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. Conclusions: Our 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. • 31P-MRS is a promising method to separate neurodegenerative diseases by identifying changes in neuroenergetic metabolisms. • Frontal PME/PDE for AD, as well as putamen PME/PDE and midbrain ATP/Pi for PD are potentially sensitive and stable markers. • PCr/Pi is a vulnerable indicator depending on the MRS methodology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (23Na) 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. [ABSTRACT FROM AUTHOR]

Background: Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease. Methods: The SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70 years old at the time of inclusion, being followed annually over 10 years. Our multimodal protocol includes structural, diffusion, functional, and sodium magnetic resonance imaging (MRI) at 3 T and 7 T, positron emission tomography (PET), blood samples, genetics, audiometry, and neuropsychological and neurological examinations as well as assessment of neuronal risk factors. Results: One hundred forty-two participants (50% females) were enrolled in the SENIOR cohort with a mean age of 60 (SD 6.3) years at baseline. Baseline results with multiple regression analyses reveal that cerebral white matter lesions can be predicted by cardiovascular and cognitive risk factors and age. Cardiovascular risk factors were strongly associated with juxtacortical and periventricular lesions. Intra-subject across-test variability as a measure of neuropsychological test performance and possible cognitive marker predicts white matter volume and is significantly associated with risk profile. Division of the cohort into subjects with a higher and lower risk profile shows significant differences in intra-subject across-test variability and volumes as well as cortical thickness of brain regions of the temporal lobe. There is no difference between the lower- and higher-risk groups in amyloid load using PET data from a subset of 81 subjects. Conclusions: We here describe the study protocol and baseline findings of the SENIOR observational study which aim is the establishment of integrated, multiparametric maps of normal aging and the identification of early biomarkers for neurodegeneration. We show that intra-subject across-test variability as a marker of neuropsychological test performance as well as age, gender, and combined risk factors influence neuronal decline as represented by decrease in brain volume, cortical thickness, and increase in white matter lesions. Baseline findings will be used as underlying basis for the further implications of aging and neuronal degeneration as well as examination of brain aging under different aspects of brain pathology versus physiological aging. [ABSTRACT FROM AUTHOR]

Background: [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 (23Na‐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 23Na‐MRI, thus improving our understanding of neuroenergetics alteration in AD. Method: 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, 23Na‐MRI and 1H‐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. Result: 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). Conclusion: For the first time, the association between local glucose consumption rates and sodium concentrations were investigated in AD using combined FDG‐PET and 23Na‐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. [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease (AD), energy deficit is suspected to occur before clinical symptoms arise. Therefore, neuroimaging methods sensitive to metabolic alterations are attractive to improve diagnostics, therapeutics and follow‐ups of AD patients. An indirect measure of deficient Na+/K+‐ATPase‐activity during neurodegeneration is provided by the tissue sodium concentration (TSC) measured by Sodium‐(23Na)‐MRI. Method: 16 patients (7 Male, 71.7±8 years) diagnosed with AD (MoCA 15.1±7) were recruited from Ste. Anne Hospital in Paris as well as 16 cognitively healthy age‐matched control subjects (7 Male, 69±3.1 years; MoCA 28.1±1.8). Each subject underwent 23Na and 1H MRI examinations at the 7T MRI scanner (Siemens) at Neurospin, CEA. A dual‐resonance 1H/23Na volume coil (Rapid Biomedical) was used for a 23Na MRI protocol acquiring ultra‐short echo‐time images (3mm isotropic resolution) at two flip‐angles (a1=25º/a2=55º) (Coste et al., 2019). Briefly, processing steps comprised image reconstruction, denoising, motion‐ and B1‐inhomogeneities‐corrections, and a calibration step using 4 external references. Individual TSC maps were co‐registered to their T1‐weighted anatomical reference (MP2RAGE, 750 µm isotropic resolution) and a partial‐volume‐effect correction (Thomas et al., 2016) was implemented to limit the influence of sodium from cerebrospinal fluid. Anatomical and TSC images were normalized to the OASIS template using ANTs. A parameter free permutation analysis was performed voxel‐wise on normalized TSC images and on the LogJacobian of the deformation fields. After, region‐of‐interest‐analyses on hippocampus from VolBrain‐Atlas followed. Result: The voxel‐based analysis showed significant widespread increases in TSC of AD patients, particularly in parietal, temporal and frontal regions. Interestingly, the observed TSC changes were located in areas not directly associated to significant structural changes (Fig 1). Furthermore, TSC in the hippocampus was found significantly higher in AD than in controls (42.9±4.3mmol/l; 35.8±3.9mmol/l; Wilcoxon‐rank‐sum; p=0.00015, z=3.8) and was correlated, after controlling for age, with both the MoCA‐scores (r=‐0.62; p=0.0002) and hippocampal volumes (r=‐0.39; p=0.032). Conclusion: High‐field quantitative 23Na MRI in AD shows increased TSC values across a wide range of brain regions. These results may provide a deeper insight into metabolic alterations occurring during neurodegeneration. 23Na MRI could therefore serve as a useful tool to characterize disease progression or the impact of therapeutic intervention. [ABSTRACT FROM AUTHOR]