Are we social enough? Use of social media among members of the Italian Society of Neurology for the study of dementia.

BACKGROUND: Clinical researchers increasingly embrace social media in their professional lives. The digital revolution has provided new routes for sharing data, disseminating results, and promoting the impact of scientific findings. In this study, we explored the attitude of the members of the Italian Society of Neurology for the study of dementia (SINdem) to use social media with the aim to set up possible corrective actions to maximize digitalization benefits at the individual and community levels. METHOD: An ad hoc designed survey was implemented and distributed to the SINdem and SINdem4Juniors communities. It explored the different use of social media taking into account frequency, type of social media use (active vs passive; professional vs private). Descriptive statistical analyses were performed alongside statistical comparisons to highlight possible differences in the use. RESULTS: We collected 133 answers showing a prominent use of social media in private life (t(132) = 21.1, p < 0.001), with SINdem4Juniors members showing a higher private use compared to the older SINdem colleagues. Professional use was mainly limited to passive activities such as following others' social profiles (t(132) = 11.9, p < 0.001). DISCUSSION: Overall scenario suggests that professional use of social media is very limited in both SINdem and SINdem4juniors communities. This evidence points to an urgent need for training interventions and top-down strategies aimed at improving collaboration, dissemination, and sharing through social media among individuals belonging to the same scientific-professional community.

Non-Pharmacological Treatments in Lewy Body Disease: A Systematic Review.

INTRODUCTION: Lewy body disease (LBD) is the second most common neurodegenerative disorder in patients older than 65 years. LBD is characterized by heterogeneous symptoms like fluctuation in attention, visual hallucinations, Parkinsonism, and REM sleep behaviour disorders. Considering the relevant social impact of the disease, identifying effective non-pharmacological treatments is becoming a priority. The aim of this systematic review was to provide an up-to-date literature review of the most effective non-pharmacological treatments in patients with LBD, focussing on evidence-based interventions. METHODS: Following PRISMA criteria, we carried out a systematic search through three databases (PubMed, Cochrane Libraries, and PEDro) including physical therapy (PT), cognitive rehabilitation (CR), light therapy (LT), transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), deep brain stimulation (DBS). All studies were qualitatively assessed using standardized tools (CARE and EPHPP). RESULTS: We obtained a total of 1,220 studies of which 23 original articles met eligibility criteria for inclusion. The total number of LBD patients included was 231; mean age was 69.98, predominantly men (68%). Some PT studies highlighted improvements in motor deficits. CR produced significant improvements in mood, cognition, and patient's quality of life and satisfaction. LT outlined a partial trend of improvements in mood and sleep quality. DBS, ECT, and TMS showed some partial improvements mainly on neuropsychiatric symptoms, whereas tDCS provided partial improvements in attention. CONCLUSION: This review highlights the efficacy of some evidence-based rehabilitation studies in LBD; however, further randomized controlled trials with larger samples are needed to provide definitive recommendations.

Molecular biomarkers correlate with brain grey and white matter changes in patients with mitochondrial m.3243A > G mutation.

INTRODUCTION: The mitochondrial DNA (mtDNA) m.3243A > G mutation in the MT-TL1 gene results in a multi-systemic disease, that is commonly associated with neurodegenerative changes in the brain. METHODS: Seventeen patients harboring the m3243A > G mutation were enrolled (age 43.1 ± 11.4 years, 10 M/7F). A panel of plasma biomarkers including lactate acid, alanine, L-arginine, fibroblast growth factor 21 (FGF-21), growth/differentiation factor 15 (GDF-15) and circulating cell free -mtDNA (ccf-mtDNA), as well as blood, urine and muscle mtDNA heteroplasmy were evaluated. Patients also underwent a brain standardized MR protocol that included volumetric T1-weighted images and diffusion-weighted MRI. Twenty sex- and age-matched healthy controls were included. Voxel-wise analysis was performed on T1-weighted and diffusion imaging, respectively with VBM (voxel-based morphometry) and TBSS (Tract-based Spatial Statistics). Ventricular lactate was also evaluated by 1H-MR spectroscopy. RESULTS: A widespread cortical gray matter (GM) loss was observed, more severe (p < 0.001) in the bilateral calcarine, insular, frontal and parietal cortex, along with infratentorial cerebellar cortex. High urine mtDNA mutation load, high levels of plasma lactate and alanine, low levels of plasma arginine, high levels of serum FGF-21 and ventricular lactate accumulation significantly (p < 0.05) correlated with the reduced brain GM density. Widespread microstructural alterations were highlighted in the white matter, significantly (p < 0.05) correlated with plasma alanine and arginine levels, with mtDNA mutation load in urine, with high level of serum GDF-15 and with high content of plasma ccf-mtDNA. CONCLUSIONS: Our results suggest that the synergy of two pathogenic mechanisms, mtDNA-related mitochondrial respiratory deficiency and defective nitric oxide metabolism, contributes to the brain neurodegeneration in m.3243A > G patients.

Major cerebral vessels involvement in patients with MELAS syndrome: Worth a scan? A systematic review.

Major cerebral vessels have been proposed as a target of defective mitochondrial metabolism in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS). Cerebral angiographic techniques are not routinely performed in MELAS patients. A systematic literature review was performed to identify studies describing major vessel caliber alterations in MELAS. Twenty-three studies reporting on 46 MELAS patients were included. Alterations in major caliber vessels were present in 59% (27/46) of patients. Dilation occurred in 37% (17/46) of patients, and in 88% (15/17) of them during a stroke-like episode (SLE). Stenosis was reported in 24% (11/46) of patients: 36% (4/11) related to an SLE and 64% (7/11) to dissections or degenerative changes. During an SLE, identification of intracranial vessels dilation or stenosis could be a selection tool for new treatment protocols. Outside SLE, identification of major cerebral vessels dissections and degenerative changes may help to prevent subsequent complications.

Association Between Gait, Cognition, and Gray Matter Volumes in Mild Cognitive Impairment and Healthy Controls.

AIMS: To assess the correlation between cognitive functioning and 3 gait parameters (gait speed, cadence, and stride length) in persons with mild cognitive impairment (MCI) and cognitively healthy controls and investigate linear correlations between gait and gray matter volumes. MATERIALS AND METHODS: Participants were recruited at IRCCS San Camillo Hospital, Venice, Italy (MCI=43; age-matched controls=43). Participants underwent comprehensive neuropsychological assessment. Gait speed, cadence, and stride length, were assessed with the BTS FREEMG 300 device. Three-dimensional (3D) T1-weighted MR images were acquired using a 1.5 T Philips Achieva MRI system with a Turbo Field Echo sequence. RESULTS: In MCI there was a positive correlation between gait speed and memory tests (P<0.05). In controls all 3 gait parameters correlated with executive functioning (P<0.01). Temporal and limbic areas (ie, superior temporal gyrus, thalamus and parahippocampal gyrus) were associated with gait parameters in MCI whereas in controls the associations were with frontal areas (ie, middle, inferior, and superior frontal gyrus) and in the cerebellum (anterior and posterior lobe). CONCLUSIONS: Our results highlight a distinct pattern of association between gray matter volume and gait parameters in MCI patients and controls (temporal areas in MCI and frontal areas in healthy elderly), suggesting a relationship between dementia-related pathology and gait dysfunction.

The largest caucasian kindred with dentatorubral-pallidoluysian atrophy: A founder mutation in italy.

BACKGROUND: Dentatorubral-pallidoluysian atrophy is a hereditary neurodegenerative disease prevalently reported in Japan but rare in Caucasians. The objective of this study was to reconstruct the pedigree of Italian dentatorubral-pallidoluysian atrophy familial cases describing their clinical features. METHODS: We investigated 6 apparently unrelated dentatorubral-pallidoluysian atrophy families comprising a total of 51 affected individuals: 13 patients were clinically examined, and for 38 patients clinical data were collected from clinical sources. The dentatorubral-pallidoluysian atrophy diagnosis was genetically confirmed in 18 patients. Genealogical data from historical archives were analyzed. RESULTS: All 6 families were unified in a large pedigree deriving from a founder couple originating from Monte San Giuliano (Italy) in the late 1500s, with 51 affected subjects over the last 4 generations. Wide phenotypical variability in age at onset and clinical features was confirmed. Epilepsy was more frequent in juvenile cases than in late adults, with cognitive/psychiatric and motor disorders observed regardless of age at onset. CONCLUSIONS: We have described the largest Caucasian dentatorubral-pallidoluysian atrophy pedigree from a single founder couple. The introduction of the dentatorubral-pallidoluysian atrophy gene in Italy could have arisen as a result of trade relationships between the Spanish or Portuguese and the Japanese in the 1500s. © 2019 International Parkinson and Movement Disorder Society.

Effects of Light Treatment on Sleep, Cognition, Mood, and Behavior in Alzheimer's Disease: A Systematic Review.

BACKGROUND: Bright light treatment is a therapeutic intervention mainly used to treat sleep and circadian disturbances in Alzheimer's disease (AD) patients. Recently, a handful of studies also focused on the effect on cognition and behavior. Conflicting findings are reported in the literature, and no definite conclusions have been drawn about its specific therapeutic effect. SUMMARY: The aim of this review is to provide a critical evaluation of available evidence in this field, highlighting the specific characteristics of effective bright light treatment. Eligible studies were required to assess at least one of the following outcome measures: sleep, cognition, mood, and/or behavior (e.g., depression, agitation). A total of 32 articles were included in this systematic review and identified as research intervention studies about light treatment in AD. The quality of the papers was evaluated based on the US Preventive Service Task Force guidelines. Key Messages: Overall, the current literature suggests that the effects of light treatment in AD patients are mixed and may be influenced by several factors, but with a general trend toward a positive effect. Bright light seems to be a promising intervention treatment without significant adverse effects; therefore, further well-designed randomized controlled trials are needed taking into account the highlighted recommendations.

White Matter Hyperintensity Load Modulates Brain Morphometry and Brain Connectivity in Healthy Adults: A Neuroplastic Mechanism?

White matter hyperintensities (WMHs) are acquired lesions that accumulate and disrupt neuron-to-neuron connectivity. We tested the associations between WMH load and (1) regional grey matter volumes and (2) functional connectivity of resting-state networks, in a sample of 51 healthy adults. Specifically, we focused on the positive associations (more damage, more volume/connectivity) to investigate a potential route of adaptive plasticity. WMHs were quantified with an automated procedure. Voxel-based morphometry was carried out to model grey matter. An independent component analysis was run to extract the anterior and posterior default-mode network, the salience network, the left and right frontoparietal networks, and the visual network. Each model was corrected for age, global levels of atrophy, and indices of brain and cognitive reserve. Positive associations were found with morphometry and functional connectivity of the anterior default-mode network and salience network. Within the anterior default-mode network, an association was found in the left mediotemporal-limbic complex. Within the salience network, an association was found in the right parietal cortex. The findings support the suggestion that, even in the absence of overt disease, the brain actuates a compensatory (neuroplastic) response to the accumulation of WMH, leading to increases in regional grey matter and modified functional connectivity.

How to enhance route learning and visuo-spatial working memory in aging: a training for residential care home residents.

OBJECTIVES: This study aimed to assess the efficacy of a route-learning training in a group of older adults living in a residential care home. We verified the presence of training-specific effects in tasks similar to those trained - route-learning tasks - as well as transfer effects on related cognitive processes - visuo-spatial short-term memory (VSSTM; Corsi Blocks Test (CBT), forward version), visuo-spatial working memory (VSWM; CBT, backward version; Pathway Span Tasks; Jigsaw Puzzle Test) - and in self-report measures. The maintenance of training benefits was examined after 3 months. METHOD: Thirty 70-90-year-old residential care home residents were randomly assigned to the route-learning training group or to an active control group (involved in non-visuo-spatial activities). RESULTS: The trained group performed better than the control group in the route-learning tasks, retaining this benefit 3 months later. Immediate transfer effects were also seen in visuo-spatial span tasks (i.e., CBT forward and backward version and Pathway Span Task); these benefits had been substantially maintained at the 3-month follow-up. CONCLUSION: These findings suggest that a training on route learning is a promising approach to sustain older adults' environmental learning and some related abilities (e.g., VSSTM and VSWM), even in residential care home residents.

Visual Perceptual Organization Ability in Autopsy-Verified Dementia with Lewy Bodies and Alzheimer's Disease.

OBJECTIVES: Prominent impairment of visuospatial processing is a feature of dementia with Lewy bodies (DLB), and diagnosis of this impairment may help clinically distinguish DLB from Alzheimer's disease (AD). The current study compared autopsy-confirmed DLB and AD patients on the Hooper Visual Organization Test (VOT), a test that requires perceptual and mental reorganization of parts of an object into an identifiable whole. The VOT may be particularly sensitive to DLB since it involves integration of visual information processed in separate dorsal and ventral visual "streams". METHODS: Demographically similar DLB (n=28), AD (n=115), and normal control (NC; n=85) participants were compared on the VOT and additional neuropsychological tests. Patient groups did not differ in dementia severity at time of VOT testing. High and Low AD-Braak stage DLB subgroups were compared to examine the influence of concomitant AD pathology on VOT performance. RESULTS: Both patient groups were impaired compared to NC participants. VOT scores of DLB patients were significantly lower than those of AD patients. The diagnostic sensitivity and specificity of the VOT for patients versus controls was good, but marginal for DLB versus AD. High-Braak and low-Braak DLB patients did not differ on the VOT, but High-Braak DLB performed worse than Low-Braak DLB on tests of episodic memory and language. CONCLUSIONS: Visual perceptual organization ability is more impaired in DLB than AD but not strongly diagnostic. The disproportionate severity of this visual perceptual deficit in DLB is not related to degree of concomitant AD pathology, which suggests that it might primarily reflect Lewy body pathology. (JINS, 2016, 22, 609-619).

Relationship between spatial ability, visuospatial working memory and self-assessed spatial orientation ability: a study in older adults.

This paper describes some novel spatial tasks and questionnaires designed to assess spatial and orientation abilities. The new tasks and questionnaires were administered to a sample of 90 older adults (41 males, age range 57-90), along with some other tests of spatial ability (Minnesota Paper Form Board, Mental Rotations Test, and Embedded Figures Test) and tests of visuospatial working memory (Corsi's Block Test and Visual Pattern Test). The internal reliability of the new tasks and questionnaires was analyzed, as well as their relationship with the spatial and working memory tests. The results showed that the new spatial tasks are reliable, correlate with working memory and spatial ability tests and, compared with the latters, show stronger correlations with the self-report questionnaires referring to orientation abilities. A model was also tested (with reference to Allen et al. in Intelligence 22:327-355, 1996) in which the new tasks were assumed to relate to spatial ability and predict orientation abilities as assessed by the self-report measures.

Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe.

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity--or the number of items in a set--which is thought to rely on an "approximate number sense" (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.

"Build Your Village"-Conducting the Village Test on Cognitively Impaired Patients: A First Journey into Alzheimerland.

BACKGROUND: This work aimed to study the Village Test (VT) in a group of patients with Alzheimer's disease (AD) and compare the results with those of a group of patients with mild cognitive impairment (MCI) and controls. METHODS: A total of 50 patients with AD, 28 patients with MCI, and 38 controls were evaluated. All participants underwent the VT and an extensive neuropsychological evaluation. RESULTS: The mean ages of the participants were 74.4 years for those with AD, 74 for those with MCI, and 70.2 for the controls. The AD group built smaller and essential villages with a scarce use of pieces, a poor use of dynamic pieces, and scarce use of human figures. All constructions were often concentrated in the center of the table. CONCLUSIONS: The villages built by the AD group represent a cognitive and affective coarctation and indicate a sense of existential disorientation and isolation. The VT is a useful aid for getting in touch with the inner emotional and existential states of patients with AD, and it could represent a complementary screening tool for orienting cognitive impairment diagnoses.

Sulcal Morphometry Predicts Mild Cognitive Impairment Conversion to Alzheimer's Disease.

Background: Being able to differentiate mild cognitive impairment (MCI) patients who would eventually convert (MCIc) to Alzheimer's disease (AD) from those who would not (MCInc) is a key challenge for prognosis. Objective: This study aimed to investigate the ability of sulcal morphometry to predict MCI progression to AD, dedicating special attention to an accurate identification of sulci. Methods: Twenty-five AD patients, thirty-seven MCI and twenty-five healthy controls (HC) underwent a brain-MR protocol (1.5T scanner) including a high-resolution T1-weighted sequence. MCI patients underwent a neuropsychological assessment at baseline and were clinically re-evaluated after a mean of 2.3 years. At follow-up, 12 MCI were classified as MCInc and 25 as MCIc. Sulcal morphometry was investigated using the BrainVISA framework. Consistency of sulci across subjects was ensured by visual inspection and manual correction of the automatic labelling in each subject. Sulcal surface, depth, length, and width were retrieved from 106 sulci. Features were compared across groups and their classification accuracy in predicting MCI conversion was tested. Potential relationships between sulcal features and cognitive scores were explored using Spearman's correlation. Results: The width of sulci in the temporo-occipital region strongly differentiated between each pair of groups. Comparing MCIc and MCInc, the width of several sulci in the bilateral temporo-occipital and left frontal areas was significantly altered. Higher width of frontal sulci was associated with worse performances in short-term verbal memory and phonemic fluency. Conclusions: Sulcal morphometry emerged as a strong tool for differentiating HC, MCI, and AD, demonstrating its potential prognostic value for the MCI population.

Exploring the neural and behavioral correlates of cognitive telerehabilitation in mild cognitive impairment with three distinct approaches.

Background: Currently, the impact of drug therapies on neurodegenerative conditions is limited. Therefore, there is a strong clinical interest in non-pharmacological interventions aimed at preserving functionality, delaying disease progression, reducing disability, and improving quality of life for both patients and their caregivers. This longitudinal multicenter Randomized Controlled Trial (RCT) applies three innovative cognitive telerehabilitation (TR) methods to evaluate their impact on brain functional connectivity reconfigurations and on the overall level of cognitive and everyday functions. Methods: We will include 110 participants with mild cognitive impairment (MCI). Fifty-five participants will be randomly assigned to the intervention group who will receive cognitive TR via three approaches, namely: (a) Network-based Cognitive Training (NBCT), (b) Home-based Cognitive Rehabilitation (HomeCoRe), or (c) Semantic Memory Rehabilitation Training (SMRT). The control group (n = 55) will receive an unstructured home-based cognitive stimulation. The rehabilitative program will last either 4 (NBTC) or 6 weeks (HomeCoRe and SMRT), and the control condition will be adapted to each TR intervention. The effects of TR will be tested in terms of Δ connectivity change, obtained from high-density electroencephalogram (HD-EEG) or functional magnetic resonance imaging at rest (rs-fMRI), acquired before (T0) and after (T1) the intervention. All participants will undergo a comprehensive neuropsychological assessment at four time-points: baseline (T0), within 2 weeks (T1), and after 6 (T2) and 12 months (T3) from the end of TR. Discussion: The results of this RCT will identify a potential association between improvement in performance induced by individual cognitive TR approaches and modulation of resting-state brain connectivity. The knowledge gained with this study might foster the development of novel TR approaches underpinned by established neural mechanisms to be validated and implemented in clinical practice.Clinical trial registration: [https://classic.clinicaltrials.gov/ct2/show/NCT06278818], identifier [NCT06278818].

Neurological Manifestations of Long COVID: A Single-Center One-Year Experience.

Purpose: We report our single-center experience on the neurological manifestations of long COVID. Patients and Methods: This is a retrospective observational study. All consecutive patients referred to the neurological long COVID outpatient clinic of our institute from January 21 2021 to December 9 2021 underwent a general neurological objective examination. Treatments and investigations (brain MRI, neuropsychological evaluation, or others) were prescribed on an individual basis as per standard clinical practice. A follow-up visit was performed when appropriate. Descriptive statistics were presented as absolute and relative frequencies for categorical variables and as means, median, and ranges for continuous variables. Results: One hundred and three patients were visited (mean age 50.5 ±36 years, 62 females). The average time from acute COVID-19 infection to the first visit to our outpatient clinic was 243 days. Most patients presented with a mild form of acute COVID-19, with only 24 cases requiring hospitalization. The neurological symptoms mostly (n=70/103, 68%) started during the acute phase (before a negative swab for SARS-CoV-2). The most frequent acute manifestations reported, which lately became persistent, were fatigue (n=58/103, 56%), olfactory/taste dysfunction (n=58/103, 56%), headache (n=47/103, 46%), cognitive disorders (n=46/103, 45%), sleep disorders (n=30/103, 29%), sensitivity alterations (n=29/103, 28%), and dizziness (n=7/103, 7%). Tremor was also reported (n=8/103, 7%). Neuropsychological evaluation was performed in 30 patients and revealed alterations in executive functions (n=6/30, 20%), memory (n=11/30, 37%), with pathological depressive (n=9/30, 30%) and anxiety (n=8/30, 27%) scores. Brain MRIs have been performed in 41 cases, revealing nonspecific abnormal findings only in 4 cases. Thirty-six patients underwent a follow-up, where a general improvement was observed but rarely (n=2/36) a complete recovery. Conclusion: The majority of patients presenting persistent neurological symptoms (most frequently fatigue, cognitive disorders, and olfactory dysfunctions) developed a previous mild form of COVID-19. Further studies are required to develop therapeutic strategies.

Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction.

OBJECTIVES: To explore the neuropsychological profile and the integrity of the olfactory network in patients with COVID-19-related persistent olfactory dysfunction (OD). METHODS: Patients with persistent COVID-19-related OD underwent olfactory assessment with Sniffin' Sticks and neuropsychological evaluation. Additionally, both patients and a control group underwent brain MRI, including T1-weighted and resting-state functional MRI (rs-fMRI) sequences on a 3 T scanner. Morphometrical properties were evaluated in olfaction-associated regions; the rs-fMRI data were analysed using graph theory at the whole-brain level and within a standard parcellation of the olfactory functional network. All the MR-derived quantities were compared between the two groups and their correlation with clinical scores in patients were explored. RESULTS: We included 23 patients (mean age 37 ± 14 years, 12 females) with persistent (mean duration 11 ± 5 months, range 2-19 months) COVID-19-related OD (mean score 23.63 ± 5.32/48, hyposmia cut-off: 30.75) and 26 sex- and age-matched healthy controls. Applying population-derived cut-off values, the two cognitive domains mainly impaired were visuospatial memory and executive functions (17 % and 13 % of patients). Brain MRI did not show gross morphological abnormalities. The lateral orbital cortex, hippocampus, and amygdala volumes exhibited a reduction trend in patients, not significant after the correction for multiple comparisons. The olfactory bulb volumes did not differ between patients and controls. Graph analysis of the functional olfactory network showed altered global and local properties in the patients' group (n = 19, 4 excluded due to artifacts) compared to controls. Specifically, we detected a reduction in the global modularity coefficient, positively correlated with hyposmia severity, and an increase of the degree and strength of the right thalamus functional connections, negatively correlated with short-term verbal memory scores. DISCUSSION: Patients with persistent COVID-19-related OD showed an altered olfactory network connectivity correlated with hyposmia severity and neuropsychological performance. No significant morphological alterations were found in patients compared with controls.

Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. METHODS: We included 29 mild-moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest-activity rhythm, chromatic pupillometry analyzed with a new data-fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. RESULTS: We demonstrated a significant thinning of the infero-temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian-impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil-light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. INTERPRETATION: Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

What Can Resting-State fMRI Data Analysis Explain about the Functional Brain Connectivity in Glioma Patients?

Resting-state functional MRI has been increasingly implemented in imaging protocols for the study of functional connectivity in glioma patients as a sequence able to capture the activity of brain networks and to investigate their properties without requiring the patients' cooperation. The present review aims at describing the most recent results obtained through the analysis of resting-state fMRI data in different contexts of interest for brain gliomas: the identification and localization of functional networks, the characterization of altered functional connectivity, and the evaluation of functional plasticity in relation to the resection of the glioma. An analysis of the literature showed that significant and promising results could be achieved through this technique in all the aspects under investigation. Nevertheless, there is room for improvement, especially in terms of stability and generalizability of the outcomes. Further research should be conducted on homogeneous samples of glioma patients and at fixed time points to reduce the considerable variability in the results obtained across and within studies. Future works should also aim at establishing robust metrics for the assessment of the disruption of functional connectivity and its recovery at the single-subject level.

In Vivo Parieto-Occipital White Matter Metabolism Is Correlated with Visuospatial Deficits in Adult DM1 Patients.

Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a (CTG) expansion in the DM protein kinase (DMPK) gene, representing the most common adult muscular dystrophy, characterized by a multisystem involvement with predominantly skeletal muscle and brain affection. Neuroimaging studies showed widespread white matter changes and brain atrophy in DM1, but only a few studies investigated the role of white matter metabolism in the pathophysiology of central nervous system impairment. We aim to reveal the relationship between the metabolic profile of parieto-occipital white matter (POWM) as evaluated with proton MR spectroscopy technique, with the visuoperceptual and visuoconstructional dysfunctions in DM1 patients. MR spectroscopy (3 Tesla) and neuropsychological evaluations were performed in 34 DM1 patients (19 F, age: 46.4 ± 12.1 years, disease duration: 18.7 ± 11.6 years). The content of neuro-axonal marker N-acetyl-aspartate, both relative to Creatine (NAA/Cr) and to myo-Inositol (NAA/mI) resulted significantly lower in DM1 patients compared to HC (p-values < 0.0001). NAA/Cr and NAA/mI correlated with the copy of the Rey-Osterrieth complex figure (r = 0.366, p = 0.033; r = 0.401, p = 0.019, respectively) and with Street's completion tests scores (r = 0.409, p = 0.016; r = 0.341, p = 0.048 respectively). The proportion of white matter hyperintensities within the MR spectroscopy voxel did not correlate with the metabolite content. In this study, POWM metabolic alterations in DM1 patients were not associated with the white matter morphological changes and correlated with specific neuropsychological deficits.