Background and Aims:

Several factors exert modulatory effects on hippocampal structural plasticity. Since fatigue and depression affect a large proportion of multiple sclerosis (MS) patients, we aimed to investigate their impact on hippocampal subfields volume. The effect of gender was also explored.

Methods:

Forty-six healthy controls (HC) and 44 early relapsing-remitting (RR) MS patients (23 females, 21 males; median disease duration 2.0 years) underwent 3.0 T MRI, clinical examination including Modified Fatigue Impact Scale (MFIS) and Montgomery-Asberg Depression Rating Scale (MADRS). Global and subregional hippocampal volumes were assessed with the cross-sectional pipeline of the Freesurfer 6.0. Normalized brain volumes (NBV) were also measured. We computed hierarchical linear regression analysis to investigate the influence of demographic, MRI structural measures, fatigue and depression on hippocampal subfields volumes. The analysis was repeated for females and males, separately.

Results:

Compared to HC, RRMS had lower NBV (p≤0.03), were more fatigued and depressed (p≤0.03). In RRMS (but not in HC) female sex was significant predictor of higher volumes of CA1, dentate gyrus complex (DC), subicular complex and bilateral hippocampal fissure (HF) (ΔR²≥0.125; p≤0.03). In female MS patients, age contributed to explain significant proportion of variance in bilateral HF volume (ΔR²≥0.263; p≤0.03). In male MS patients, higher cognitive fatigue was related to lower bilateral DC and right CA1 volumes (ΔR²≥0.190; p≤0.05).

Conclusions:

These results suggest a protective effect of female gender on hippocampal volumes in RRMS, and a detrimental influence of fatigue on DC and right CA1 volumes in male RRMS patients.

Background and Aims:

To investigate resting state (RS) functional connectivity (FC) and white matter (WM) microstructural abnormalities underlying executive function (EF) impairment in multiple sclerosis (MS).

Methods:

One-hundred and sixteen MS patients and 65 age- and sex-matched healthy controls (HC) underwent 3T brain T1-weighted, RS and diffusion-weighted sequences and Wisconsin Card Sorting Test (WCST) to test EF. The main large-scale brain RS cognitive networks were derived with independent component analysis. Mean fractional anisotropy (FA) was calculated from a priori-selected WM tracts. Associations between WCST scores and RS FC and FA abnormalities were investigated with multivariable models.

Results:

In MS patients, independent predictors of working memory/updating (WCST achieved categories) were: lower corpus callosum (CC) genu FA, lower left working-memory network (WMN) (precuneus), right WMN (middle temporal gyrus) RS FC for worse performance; lower executive control network (ECN) (superior temporal gyrus), higher default-mode network (DMN) (superior parietal lobule) and salience network (SN) (superior frontal gyrus, SFG) RS FC for better performance (R2=0.35). Predictors of attention (WCST errors) were lower CC genu FA, lower left WMN (precuneus) and DMN (anterior cingulate gyrus) RS FC for worse performance; higher left WMN (cerebellum lobule IX) and ECN (SFG) RS FC for better performance (R2=0.24). Predictors of inhibition (WCST perseverative errors/responses) were lower CC genu and superior cerebellar peduncle (SCP) FA, lower left WMN (precuneus) RS FC for worse performance; and higher ECN (SFG) RS FC for better performance (R2=0.24).

Conclusions:

CC and SCP microstructural damage and RS FC abnormalities in cognitive networks underlie EF frailty in MS.

Background and Aims:

Functional Neurological Disorders (FNDs) and Autism Spectrum Disorders (ASDs) are two common neuropsychiatric conditions sharing some common features, in terms of deficits in emotion regulation and impairment in sensory sensitivity, proprioception and interoception. Aims of this study were: (i) to assess the prevalence of autistic traits in a sample of adult patients with FNDs; (ii) to assess the prevalence of FNS in a sample of adult patients with ASDs without intellectual disabilities; in this sample, we also aimed to assess the presence of a possible association between sensory sensibility and FNS.

Methods:

Twenty-one patients with FNDs, 30 individuals with ASDs without intellectual disabilities and 45 neurotypical healthy controls (HN) completed: (i) the Autism Quotient (AQ); (ii) the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R); (iii) an ad-hoc questionnaire assessing the presence of specific functional neurological symptoms (FNS). ASDs participants also completed the Sensory Perception Quotient - Short Form (SPQ-SF), assessing sensory sensibility.

Results:

In the FNDs sample, no patient scored above the clinical cut-off at the AQ and the 19% scored above the cut-off at the RAADS; this prevalence was similar to the one we found in HN. Conversely, the 86.7% of participants with ASDs reported at least one FNS, a prevalence significantly higher than the one encountered in HN. In the ASDs sample, the SPQ-SF Total Score and the total number of FNS negatively correlated.

Conclusions:

FNDs individuals did not present autistic traits more than HN. ASDs individuals presented a higher number of FNS than HN; this rate was associated with a lower sensory sensibility.

Background and Aims:

Patients with dementia may be vulnerable to SARS-CoV 2 infection. Dementia is considered a relevant risk of adverse outcomes among COVID-19 patients. The aims of this study were to evaluate the incidence of SARS-CoV-2 infection and mortality in a cohort of patients with dementia living in the Lazio Region and to identify predicting factors for infection and death.

Methods:

We conducted a population-based study using health care administrative databases. We enrolled dementia patients, 65 aged or over, residing in the Lazio Region. Each patient was followed between January, 2020 and February, 2021 to ascertain SARS-CoV-2 infection and up to December 2020 to assess mortality. Univariate and multivariable binomial regression models were used to estimate risk of infection and death. A multivariable logistic regression model was fitted to test a large number of factors as possible determinants of two outcome.

Results:

Among 37,729 dementia patients (mean age 82 years), 7% were diagnosed with SARS-CoV-2 infection during the follow up, and among these 31% died. Women, patients with cerebrovascular diseases, pneumonia, blood’s diseases, femur fracture, anxiety, and those using antipsychotic or antithrombotic agents had higher infection probability. Males, the oldest patients, not resident in Rome, with symptoms at SARS-COV-2 diagnosis, those using antipsychotic, antithrombotic or antibacterial agents had higher odds of death.

Conclusions:

Our findings revealed that there are disease-specific differences in infection susceptibility among dementia patients and highlight the need to protect these group of patients as part of the strategy to control the COVID-19 effects.

Background and Aims:

Peripheral monocytes can penetrate into the CNS and contribute to neuroinflammation, a key event in the pathogenesis of Alzheimer’s disease (AD). TSPO receptor is expressed on monocytes’ surface and plays a role in their chemotaxis. The present study aims to investigate the role of TSPO in the regulation of Aβ1-42 induced chemotaxis in the context of AD pathology. Moreover, the effect of anti-inflammatory drugs Donepezil, by its interaction with α7 nAchR, and Co-ultraPEALut on peripheral immune cells chemotactic properties has been evaluated.

Methods:

Chemotaxis experiment were performed on both monocytic cell lines and monocytes from AD patients and controls. Oligomeric Aβ1-42 (125 pM) was used as chemoattractant; in addition, TSPO ligands, Co-ultraPEALut and Donepezil were tested. Boyden chamber assay was used to evaluate chemotactic properties.

Results:

Oligomeric Aβ1-42 significantly induced monocyte chemotaxis. TSPO selective inhibitor PK11195 was able to partially revert Aβ-induced chemotaxis in a concentration dependent manner; at the same time, agonists Emapunil and Ro5-4864 increased chemotaxis respect to vehicle (p<0.05). As for Co-ultraPEALut, it was able to prevent the increase in Aβ-induced chemotaxis in a concentration dependent manner. Lastly, preliminary results showed inhibition of Aβ-induced migration in human monocytes from healthy controls (p<0.001) by means of Donepezil.

Conclusions:

Taken together, these findings suggest the involvement of TSPO in the chemotaxis of peripheral monocytes. Co-ultraPEALut emerges as a useful therapeutic agent to reduce neuroinflammation in AD by modulating monocytes chemotaxis. Ongoing experiments are now considering the specific role of α7 nAchR in Aβ-induced chemotaxis in AD patients.

Background and Aims:

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia. However, clinical diagnosis can be challenging. Two toolkits have been deverloped to aid the clinical diagnosis of DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). The aim of the present study is to evaluate the diagnostic accuracy of these two questionnaires, as well as their capacity to enhance application and interpretation of the Consensus Criteria.

Methods:

In this study, LBCRS and AT-DLB were distributed to 135 Cognitive Decline and Dementia Centers (CDCD). We asked to administer the two questionnaires to all patients referred within the following three months, independently from the clinical diagnosis, and also to apply Consensus Criteria for DLB diagnosis, according to the results of each of the two toolkits, to all subjects.

Results:

A total of 23 Centers participated to the survey, and 2006 patients were enrolled. Diagnosis of dementia was not concordant in 152 (7.58%) subjects, who were excluded from the cohort. Of the 1854 remaining patients, 56.53% were female; the mean age was 75.06±14.58 years. LBCRS toolkit showed a good reliability (Cronbach-alpha=0.77), even when removing variables from the construct Conversely, AT-DLB toolkit Cronbach-alpha was 0.52 and, after the subtraction of the “cognitive fluctuation” criterion, was only 0.31.

Conclusions:

In a clinical setting, LBCRS questionnaire shows a better diagnostic accuracy for DLB diagnosis than AT-DLB questionnaire. Further investigations should focus on the assessment of LBCRS capacity to identify DLB patients at prodromal stages.

Background and Aims:

Background: Several preclinical and clinical investigations have claimed a strong relationship between neuroinflammation and Alzheimer’s disease pathology in the brain. No study evaluated the effect of acute neuroinflammation on CSF levels of amyloid and tau markers in vivo.

Objective: evaluate the correlation between acute neuroinflammation, neuronal, glial and amyloid markers in CSF of subjects with acute inflammation of the brain

Methods:

Methods: Sixty subjects who underwent CSF analyses were included, namely 42 encephalitis (ENC), and 18 healthy controls (HC). Each subject underwent an extended panel of CSF markers, namely Aβ40, 42 and 38, neuronal (NfL, T-tau), and glial (GFAP) testing. Linear and non-linear correlations between CSF biomarkers were evaluated studying conditional independence relationships following a graphical model approach.

Results:

Results: ENC showed increased CSF levels of neuronal/glial markers whereas amyloid related markers (aβ40, 42 and 38) did not differ compared to controls. No correlation was observed between levels of neuronal/glial and Aβ markers in conditional independence analysis.

Conclusions:

Conclusions: this is the first demonstration based on CSF biomarkers that acute neuroinflammation does not directly impact on amyloid pathways but correlated with glial and neuronal markers in vivo.