93 research outputs found
Comparing Cerebellar tDCS and Cerebellar tACS in Neurodegenerative Ataxias Using Wearable Sensors: A Randomized, Double-Blind, Sham-Controlled, Triple-Crossover Trial
No full textCerebellar transcranial direct current stimulation (tDCS) represents a promising therapeutic approach for both motor and cognitive symptoms in neurodegenerative ataxias. Recently, transcranial alternating current stimulation (tACS) was also demonstrated to modulate cerebellar excitability by neuronal entrainment. To compare the effectiveness of cerebellar tDCS vs. cerebellar tACS in patients with neurodegenerative ataxia, we performed a double-blind, randomized, sham controlled, triple cross-over trial with cerebellar tDCS, cerebellar tACS or sham stimulation in twenty-six participants with neurodegenerative ataxia. Before entering the study, each participant underwent motor assessment with wearable sensors considering gait cadence (steps/minute), turn velocity (degrees/second) and turn duration (seconds), and a clinical evaluation with the scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). After each intervention, participants underwent the same clinical assessment along with cerebellar inhibition (CBI) measurement, a marker of cerebellar activity. The gait cadence, turn velocity, SARA, and ICARS significantly improved after both tDCS and tACS, compared to sham stimulation (all p<0.010). Comparable effects were observed for CBI (p<0.001). Overall, tDCS significantly outperformed tACS on clinical scales and CBI (p<0.01). A significant correlation between changes of wearable sensors parameters from baseline and changes of clinical scales and CBI scores was detected. Cerebellar tDCS and cerebellar tACS are effective in ameliorating symptoms of neurodegenerative ataxias, with the former being more beneficial than the latter. Wearable sensors may serve as rater-unbiased outcome measures in future clinical trials. Identifier: NCT05621200
Association of APOE genotype with blood-brain barrier permeability in neurodegenerative disorders
No full textApolipoprotein E (APOE) is recognized for its role in modulating blood-brain barrier (BBB) permeability in vitro, which may have significant implications for the pathogenesis and progression of neurodegenerative disorders. However, evidence in vivo is contrasting. This study explores the impact of APOE genotypes on BBB integrity among 230 participants experiencing cognitive impairment, encompassing cases of Alzheimer's disease (AD) as well as various non-AD neurodegenerative conditions. To assess BBB integrity, we utilized cerebrospinal fluid (CSF)/serum albumin ratios and CSF/serum kappa and lambda free light chains (FLCs) as indirect markers. Our findings show a dose-dependent increase in BBB permeability in individuals carrying the APOE e4 allele, marked by elevated CSF/serum albumin and FLCs ratios, with this trend being especially pronounced in AD patients. These results highlight the association of APOE epsilon 4 with BBB permeability, providing valuable insights into the pathophysiology of neurodegenerative diseases
Sex influences clinical phenotype in frontotemporal dementia
No full textINTRODUCTION: Frontotemporal dementia (FTD) encompasses a wide spectrum of genetic, clinical, and histological findings. Sex is emerging as a potential biological variable influencing FTD heterogeneity; however, only a few studies explored this issue with nonconclusive results. OBJECTIVE: To estimate the role of sex in a single-center large cohort of FTD patients. METHODS: Five hundred thirty-one FTD patients were consecutively enrolled. Demographic, clinical, and neuropsychological features, survival rate, and serum neurofilament light (NfL) concentration were determined and compared between sex. RESULTS: The behavioral variant of FTD was more common in men, whereas primary progressive aphasia was overrepresented in women (p < 0.001). While global cognitive impairment was comparable, females had a more severe cognitive impairment, namely in Trail Making Test parts A and B (p = 0.003), semantic fluency (p = 0.03), Short Story Recall Test (p = 0.003), and the copy of Rey Complex Figure (p = 0.005). On the other hand, men exhibited more personality/behavioral symptoms (Frontal Behavior Inventory [FBI] AB, p = 0.003), displaying higher scores in positive FBI subscales (FBI B, p < 0.001). In particular, apathy (p = 0.02), irritability (p = 0.006), poor judgment (p = 0.033), aggressivity (p = 0.008), and hypersexuality (p = 0.006) were more common in men, after correction for disease severity. NfL concentration and survival were not statistically different between men and women (p = 0.167 and p = 0.645, respectively). DISCUSSION: The present study demonstrated that sex is a potential factor in determining FTD phenotype, while it does not influence survival. Although the pathophysiological contribution of sex in neurodegeneration is not well characterized yet, our findings highlight its role as deserving biological variable in FTD
The Impact of Insulin Resistance on Grey Matter Changes Along the Alzheimer’s Disease Continuum Insulin Resistance and Grey Matter in AD
No full textAbstract Background and Objectives Insulin resistance is emerging as a modifiable risk factor for Alzheimer’s, though its impact on grey matter volume across clinical stages remains poorly understood. The objective of the research is to investigate how insulin resistance affects grey matter integrity across the Alzheimer’s disease continuum using structural MRI. Methods Imaging, clinical, and metabolic data were extracted from 374 non-diabetic participants within the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Participants were classified as cognitively impaired (CI: n=186; 137 mild cognitive impairment, 49 early-to-moderate dementia; all AD biomarker positive) or cognitively unimpaired (CU: n=188; 122 amyloid-negative, 66 amyloid-positive). Insulin resistance was assessed at the time of MRI and clinical evaluation using the dichotomized triglyceride-glucose index (TyG). The Interactions between TyG and diagnostic group on grey matter volume were investigated using both voxel-wise and region-of-interest (ROI) based analyses, adjusted for age, sex, education, vascular risk factors, and global cognitive performance across the AD continuum. Results Insulin resistance significantly impacted gray matter volume across the AD continuum, demonstrating stage-dependent effects. In early AD disease stages, insulin resistance was associated with lower grey matter volume in fronto-parietal regions, a finding that extended to several cortical areas in CI individuals. Temporal and fronto-limbic regions were particularly highlighted by the IR-diagnosis interaction. In amyloid-positive CU individuals, IR was linked to bilateral temporal atrophy, in contrast to amyloid-negative CU participants. Discussion This study underscores the impact of insulin resistance on brain structure across the AD continuum, particularly within key vulnerability areas characteristic of AD pathology. These findings highlight the need for future research into potential therapeutic strategies targeting insulin signaling to mitigate neurodegeneration in AD
The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease
No full textAbstract INTRODUCTION Growing evidence suggests a connection between insulin resistance and apolipoprotein E ( APOE ) genotype in Alzheimer's disease (AD) pathogenesis, but the mechanisms are unclear. We examined effects of insulin resistance and APOE genotype on blood–brain barrier (BBB) integrity in AD. METHODS BBB integrity was measured in 196 biologically‐confirmed non‐diabetic patients with AD evaluating CSF/serum albumin ratio, kappa and lambda free light chains (FLCs). Insulin resistance was assessed using triglyceride–glucose index (TyG). The impact of TyG on BBB integrity, and its interaction with APOE genotypes, was analyzed using multivariate models. RESULTS Sixty‐four percent of patients with AD showed altered TyG, with the 21.8% classified as high TyG. TyG subgroups were associated with BBB abnormalities, with similar AD clinical and biomarkers profile. A significant interaction between TyG and APOE ε4/ε4 genotype on BBB permeability was found in multivariate analyses. DISCUSSION Insulin resistance is a common feature in non‐diabetic AD and correlates with altered BBB permeability, interacting synergistically with APOE genotype. Highlights Insulin resistance and apolipoprotein E ( APOE ) genotype are well‐recognized risk factors for Alzheimer's disease (AD). Insulin resistance shows high prevalence in patients with AD. Insulin resistance is related to damage in blood–brain barrier (BBB) integrity. The association between the triglyceride–glucose (TyG) index and BBB permeability varies in relation to APOE genotype; patients with the APOE ε4/ε4 displayed higher BBB permeability
Defining the Role of Frailty in the Transition from Mild Cognitive Impairment to Dementia and in Dementia Progression
No full textIntroduction: Neurodegenerative diseases are a growing concern in an aging global population. Frailty, often conceptualized as a state of diminished physiological reserve and increased susceptibility to stressors, emerges as a pivotal factor in this context. While frailty may be modified, it is essential to recognize its frequently irreversible nature, necessitating a careful approach when considering its role and influence in the progression from mild cognitive impairment (MCI) to dementia and within dementia progression. Methods: A retrospective study including 1,284 participants, attending a Cognitive Disturbances and Dementia unit from January 2021 to May 2023, was conducted. Frailty was assessed using the clinical frailty scale (CFS) score. Multilevel univariate and multivariate logistic regression models were developed to determine the contributions of patient characteristics, including frailty, to disease progression. Results: Frailty significantly increased with higher global clinical dementia rating (CDR) subgroups, suggesting escalating frailty burden with disease progression. Age, CFS, and mini-mental state examination (MMSE) scores were significant predictors of progression from MCI to dementia and to more severe dementia stages, even when considering the independence from variables contributing to frailty. Patients transitioning to a higher CDR group exhibited higher CFS scores. Age, education, anticholinergic burden, cumulative illness rating scale - geriatric, MMSE, and neuropsychiatric inventory scores significantly contributed to frailty. Conclusions: Frailty plays a critical role in the transition from MCI to dementia and within dementia progression. Age, cognitive impairment, and frailty were identified as significant predictors of disease progression. The CFS is a clinically applicable tool for frailty assessment. Regular frailty assessments may be valuable in early detection and management of dementia
Unveiling New Genetic Variants Associated with Age at Onset in Alzheimer's Disease and Frontotemporal Lobar Degeneration Due to C9orf72 Repeat Expansions
No full textAlzheimer's disease (AD) and Frontotemporal lobar degeneration (FTLD) represent the most common forms of neurodegenerative dementias with a highly phenotypic variability. Herein, we investigated the role of genetic variants related to the immune system and inflammation as genetic modulators in AD and related dementias. In patients with sporadic AD/FTLD (n = 300) and GRN/C9orf72 mutation carriers (n = 80), we performed a targeted sequencing of 50 genes belonging to the immune system and inflammation, selected based on their high expression in brain regions and low tolerance to genetic variation. The linear regression analyses revealed two genetic variants: (i) the rs1049296 in the transferrin (TF) gene, shown to be significantly associated with age at onset in the sporadic AD group, anticipating the disease onset of 4 years for each SNP allele with respect to the wild-type allele, and (ii) the rs7550295 in the calsyntenin-1 (CLSTN1) gene, which was significantly associated with age at onset in the C9orf72 group, delaying the disease onset of 17 years in patients carrying the SNP allele. In conclusion, our data support the role of genetic variants in iron metabolism (TF) and in the modulation of the calcium signalling/axonal anterograde transport of vesicles (CLSTN1) as genetic modulators in AD and FTLD due to C9orf72 expansions
Unravelling neurotransmitters impairment in primary progressive aphasias
No full text: Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tailored therapeutic approaches. In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of magnetic resonance imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 103 PPA patients and 80 age-matched healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in PPA patients (relative to HC) are correlated with specific neurotransmitter systems. As compared to HC, voxel-based brain changes in PPA were significantly associated with spatial distribution of serotonin, dopamine, and glutamatergic pathways (p < .05, False Discovery Rate corrected-corrected). Disease severity was negatively correlated with the strength of GMV colocalization of D1 receptors (p = .035) and serotonin transporter (p = .020). Moreover, we observed a significant negative correlation between positive behavioural symptoms, as measured with Frontal Behavioural Inventory, and GMV colocalization of D1 receptors (p = .007) and serotonin transporter (p < .001). This pilot study suggests that JuSpace is a helpful tool to indirectly assess neurotransmitter deficits in neurodegenerative dementias and may provide novel insight into disease mechanisms and associated clinical features
Wi-Fi channel frequency response database for contactless human activity recognition
No full textThis database collects the channel frequency response (CFR) vectors captured through the Nexmon CSI extraction tool from an Asus RT-AC86U IEEE 802.11ac Wi-Fi router working with a total bandwidth of 80 MHz. The dataset is collected in three different environments, i.e., a bedroom, a living room and a University laboratory, while one person performs one among seven activities of interest within the room. The CFR data for the empty room (E) is also provided.
We obtained data from three volunteers (a male, and two females) while they were walking (W) or running (R) around, jumping (J) in place, sitting (L) or standing (S) somewhere in the room, sitting down and standing up (C) continuously, and doing arm gym (H).
Each CFR sample results in complex-valued channel information from 242 data sub-channels for each transmit-receive antennas pair. In our experiments, with one transmitter antenna and four at the monitoring device, each sample corresponds to four vectors of 242 complex values. Although the total number of sub-channels at 80 MHz is 256, each antenna vector has 242 components as the CFR is only provided for data sub-channels, namely sub-channels whose indexes are {-122, ..., -2} and {2, ..., 122}, i.e., no CFR value is provided for the control sub-channels. For more information about the setup, please, refer to the related publication.
This dataset was used to design and assess the performance of SHARP presented in the article ''SHARP: Environment and Person Independent Activity Recognition with Commodity IEEE 802.11 Access Points'' by Francesca Meneghello, Domenico Garlisi, Nicolò Dal Fabbro, Ilenia Tinnirello, Michele Rossi.
The Python source code is available at https://github.com/signetlabdei/SHARP.
If you use this dataset, please cite our paper: @misc{meneghello2022SHARP,
url = {https://arxiv.org/abs/2103.09924},
author = {Meneghello, Francesca and Garlisi, Domenico and Fabbro, Nicolò Dal and Tinnirello, Ilenia and Rossi, Michele},
title = {Environment and Person Independent Activity Recognition with a Commodity IEEE 802.11ac Access Point},
publisher = {arXiv},
year = {2021}
Bartolomeo Carli Piccolomini, Trattato del perfetto cancelliere e altri scritti, edizione critica, introduzione e note a cura di Germano Pallini; con una premessa di Jean-Louis Fournel
No full textRicordato a lungo come discepolo e amico di Claudio Tolomei, Bartolomeo Carli Piccolomini (1503-1538) fu uno dei letterati e degli uomini politici più importanti ed influenti nella storia di Siena del primo Cinquecento. È merito di Germano Pallini aver rinnovato l’interesse per questo personaggio e per il suo Trattato del Perfetto Cancelliere, diviso in due libri e datato 7 novembre 1529. Già nel 1985 Rita Belladonna pubblicava una trascrizione diplomatica dell’intero Trattato condotta sul s..
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