Modafinil-Induced changes in functional connectivity in the cortex and cerebellum of healthy elderly subjects

In the past few years, cognitive enhancing drugs (CEDs) have gained growing interest and the focus of investigations aimed at exploring their use to potentiate the cognitive performances of healthy individuals. Most of this exploratory CED-related research has been performed on young adults. However, CEDs may also help to maintain optimal brain functioning or compensate for subtle and or subclinical deficits associated with brain aging or early-stage dementia. In this study, we assessed effects on resting state brain activity in a group of healthy elderly subjects undergoing acute administration of modafinil, a wakefulness-promoting agent. To that aim, participants (n = 24) were investigated with resting state functional Magnetic Resonance Imaging (rs-fMRI) before and after the administration of a single dose (100 mg) of modafinil. Effects were compared to age and size-matched placebo group. Rs-fMRI effects were assessed, employing a graph-based approach and Eigenvector Centrality (EC) analysis, by taking in account topological changes occurring in functional brain networks. The main finding of the study is that modafinil promotes enhanced centrality, a measure of the importance of nodes within functional networks, of the bilateral primary visual (V1) cortex. EC analysis also revealed that modafinil-treated subjects show increased functional connectivity between the V1 and specific cerebellar (Crus I, Crus II, VIIIa lobule) and frontal (right inferior frontal sulcus and left middle frontal gyrus) regions. Present findings provide functional data supporting the hypothesis that modafinil can modulate the cortico-cerebellar connectivity of the aging brai

On the critical slowing down exponents of mode coupling theory

A method is provided to compute the parameter exponent $\lambda$ yielding the dynamic exponents of critical slowing down in mode coupling theory. It is independent from the dynamic approach and based on the formulation of an effective static field theory. Expressions of $\lambda$ in terms of third order coefficients of the action expansion or, equivalently, in term of six point cumulants are provided. Applications are reported to a number of mean-field models: with hard and soft variables and both fully-connected and dilute interactions. Comparisons with existing results for Potts glass model, ROM, hard and soft-spin Sherrington-Kirkpatrick and p-spin models are presented.Comment: 4 pages, 1 figur

Disability through COVID-19 pandemic: neurorehabilitation cannot wait.

Coronavirus disease 2019 (CoViD-19) pandemic is strongly impacting all domains of our healthcare systems, including rehabilitation. In Italy, the first hit European country, medical activities were postponed to allow shifting of staff and facilities to intensive care, with neurorehabilitation limited to time-dependent diseases, <sup>1</sup> including CoViD-19 complications. <sup>2,3</sup> Hospital access to people with chronic neurodegenerative conditions such as multiple sclerosis, movement disorders or dementia, more at risks of serious consequences from the infection, <sup>4</sup> has been postponed. Patients also seek less for hospital care, with over 50% reduced stroke admissions as from an Italian survey, <sup>5</sup> possibly in fear of being infected or denied to see their families after being hospitalized. This situation can be bearable only for a short time, as any initial freezing reaction to a danger

The Ising M-p-spin mean-field model for the structural glass: continuous vs. discontinuous transition

The critical behavior of a family of fully connected mean-field models with quenched disorder, the $M-p$ Ising spin glass, is analyzed, displaying a crossover between a continuous and a random first order phase transition as a control parameter is tuned. Due to its microscopic properties the model is straightforwardly extendable to finite dimensions in any geometry.Comment: 10 pages, 1 figure, 1 tabl

Psychiatric profile of motor subtypes of de novo drug-naïve Parkinson's disease patients

Background: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder. It is well established that different motor subtypes of PD evolve with different clinical courses and prognoses. The complete psychiatric profile underlying these different phenotypes since the very early stage of the disease is debated. Aims of the study: We aimed at investigating the psychiatric profile of the three motor subtypes of PD (akinetic-rigid, tremor-dominant, and mixed) in de novo drug-naïve patients with PD. Methods: Sixty-eight patients with PD, divided into 39 akinetic-rigid (AR), seven mixed (MIX), and 22 tremor-dominant (TD) patients underwent a complete assessment of psychiatric, cognitive, and motor symptoms. Results: No significant differences were found among groups. Conclusions: Our results suggest that a differentiation of the psychiatric symptoms associated with specific motor subtypes of PD is not detectable in de novo drug-naïve patients. Previous evidence that emerges later along the disease progression may be a consequence of the dopaminergic and nondopaminergic damage increase

Supramolecular self-associating amphiphiles: determination of molecular self-association properties and calculation of critical micelle concentration using a high-throughput, optical density based methodology

Supramolecular self-associating amphiphiles are a class of amphiphilic salt, the anionic component of which is 'frustrated' in nature, meaning multiple hydrogen bonding modes can be accessed simultaneously. Here we derive critical micelle concentration values for four supramolecular self-associating amphiphiles using the standard pendant drop approach and present a new high-throughput, optical density measurement based methodology, to enable the estimation of critical micelle concentrations over multiple temperatures. In addition, we characterise the low-level hydrogen bonded self-association events in the solid state, through single crystal X-ray diffraction, and in polar organic DMSO-d(6) solutions using a combination of H-1 NMR techniques. Moving into aqueous ethanol solutions (EtOH/H2O or EtOH/D2O (1 : 19 v/v)), we also show these amphiphilic compounds to form higher-order self-associated species through a combination of H-1 NMR, dynamic light scattering and zeta potential studies

Testing for the myth of cognitive reserve. Are the static and dynamic cognitive reserve indexes a representation of different reserve warehouses?

Background: Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Years of formal education express the static measure of reserve (sCR). A dynamic aspect of CR (dCR) has been recently proposed. Objective: The aim of the study was to compare sCR and dCR indexes, respectively, to detect brain abnormalities in Alzheimer's disease (AD) patients. Methods: 117 individuals [39 AD, 40 amnestic mild cognitive impairment (aMCI), 38 healthy subjects (HS)] underwent neuropsychological evaluation and a 3T-MRI. T1-weighted volumes were used for manual segmentation of the hippocampus and of the parahippocampal cortices. Years of formal education were used as an index of sCR. Partial Least Square analysis was used to decompose the variance of individual MMSE scores, considered as a dCR index. In aMCI and AD patients, the brain abnormalities have been assessed comparing individuals with high and low levels of sCR and dCR in turn. Moreover, we investigated the effect of the different CR indexes in mediating the relationship between changes in brain volumes and memory performances. Results: sCR and dCR indexes classified differently individuals having high or low levels of CR. Smaller hippocampal and parahippocampal volumes in high dCR patients were found. The sCR and dCR indexes mediated significantly the relationship between brain abnormalities and memory in patients. Conclusions: CR mediated the relationship between brain and memory dysfunctions. We hypothesized that sCR and dCR indexes are a representation of different warehouses of reserve not operating in parallel but forming a complex system, in which crystalized cognitive abilities and actual cognitive efficiency interact with brain atrophy impacting on memory

Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

The risk for Alzheimer's disease (AD) is associated with the presence of the ?4 allele of Apolipoprotein E (APOE) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-?4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE-?4 and RNF219/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients

Movements execution in amnestic mild cognitive impairment and Alzheimer's disease.

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and {early} Alzheimer's Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD