Increased Functional Connectivity in the Default Mode Network in Mild Cognitive Impairment: A Maladaptive Compensatory Mechanism Associated with Poor Semantic Memory Performance

Semantic memory decline and changes of default mode network (DMN) connectivity have been reported in mild cognitive impairment (MCI). Only a few studies, however, have investigated the role of changes of activity in the DMN on semantic memory in this clinical condition. The present study aimed to investigate more extensively the relationship between semantic memory impairment and DMN intrinsic connectivity in MCI. Twenty-one MCI patients and 21 healthy elderly controls matched for demographic variables took part in this study. All participants underwent a comprehensive semantic battery including tasks of category fluency, visual naming and naming from definition for objects, actions and famous people, word-association for early and late acquired words and reading. A subgroup of the original sample (16 MCI patients and 20 healthy elderly controls) was also scanned with resting state functional magnetic resonance imaging and DMN connectivity was estimated using a seed-based approach. Compared with healthy elderly, patients showed an extensive semantic memory decline in category fluency, visual naming, naming from definition, words-association, and reading tasks. Patients presented increased DMN connectivity between the medial prefrontal regions and the posterior cingulate and between the posterior cingulate and the parahippocampus and anterior hippocampus. MCI patients also showed a significant negative correlation of medial prefrontal gyrus connectivity with parahippocampus and posterior hippocampus and visual naming performance. Our findings suggest that increasing DMN connectivity may contribute to semantic memory deficits in MCI, specifically in visual naming. Increased DMN connectivity with posterior cingulate and medio-temporal regions seems to represent a maladaptive reorganization of brain functions in MCI, which detrimentally contributes to cognitive impairment in this clinical population

The NeuroDante Project: Neurometric measurements of participant’s reaction to literary auditory stimuli from dante’s “divina commedia”

Neurodante. Progetto di analisi neurometrica di alcuni brani della Commedi

Development of a psychiatric disorder linked to cerebellar lesions

Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with long-term behavioral and neuropsychiatric symptoms. A 43-year-old woman with a cerebellum arteriovenous malformation and history of behavioral dysregulation since childhood is described. After the rupture of the cerebellar malformation in adulthood, her behavior morphed into specific psychiatric symptoms and cognitive deficits occurred. The neuropsychological assessment evidenced impaired performance in attention, visuospatial, memory, and language domains. Moreover, psychiatric assessment indicated a borderline personality disorder. Brain MRI examination detected macroscopic abnormalities in the cerebellar posterior lobules VI, VIIa (Crus I), and IX, and in the posterior area of the vermis, regions usually involved in cognitive and emotional processing. The described patient suffered from cognitive and behavioral symptoms that are part of the cerebellar cognitive affective syndrome. This case supports the hypothesis of a cerebellar role in personality disorders emphasizing the importance of also examining the cerebellum in the presence of behavioral disturbances in children and adults

Alginate Formulations: Current Developments in the Race for Hydrogel-Based Cardiac Regeneration

Cardiovascular diseases, including myocardial infarction (MI), represent the main worldwide cause of mortality and morbidity. In this scenario, to contrast the irreversible damages following MI, cardiac regeneration has emerged as a novel and promising solution for in situ cellular regeneration, preserving cell behavior and tissue cytoarchitecture. Among the huge variety of natural, synthetic, and hybrid compounds used for tissue regeneration, alginate emerged as a good candidate for cellular preservation and delivery, becoming one of the first biomaterial tested in pre-clinical research and clinical trials concerning cardiovascular diseases. Although promising results have been obtained, recellularization and revascularization of the infarcted area present still major limitations. Therefore, the demand is rising for alginate functionalization and its combination with molecules, factors, and drugs capable to boost the regenerative potential of the cardiac tissue. The focus of this review is to elucidate the promising properties of alginate and to highlight its benefits in clinical trials in relation to cardiac regeneration. The definition of hydrogels, the alginate characteristics, and recent biomedical applications are herewith described. Afterward, the review examines in depth the ongoing developments to refine the material relevance in cardiac recovery and regeneration after MI and presents current clinical trials based on alginate

Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients' cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation

Associations between neuropsychiatric symptoms and Alzheimer’s disease biomarkers in people with mild cognitive impairment

Background: Neuropsychiatric symptoms (NPS) are associated with faster decline in mild cognitive impairment (MCI). This study aimed to investigate the association between NPS severity and Alzheimer’s disease (AD) biomarkers, i.e., amyloid-β (Aβ), phosphorylated tau protein (p-tau) and hippocampal volume ratio (HR), to characterise in more detail MCI patients with a poor prognosis. Methods: A total of 506 individuals with MCI and 99 cognitively unimpaired older adults were selected from the ADNI dataset. The patients were divided into three different groups based on their NPI-Q total scores: no NPS (n = 198), mild NPS (n = 160) and severe NPS (n = 148). Regression models were used to assess the association between the severity of NPS and each biomarker level and positivity status. Results: Cerebrospinal fluid Aβ levels were positively associated with older age and lower MMSE scores, while higher p-tau levels were associated with female sex and lower MMSE scores. Only patients with severe NPS had a lower HR (β = −0.18, p = 0.050), i.e., more pronounced medio-temporal atrophy, than those without NPS. Discussion: Only HR was associated with the presence of NPS, partially in line with previous evidence showing that severe NPS may be explained primarily by greater grey matter loss. Future longitudinal studies will be needed to ascertain the relevance of this finding

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

Associations between Neuropsychiatric Symptoms and Alzheimer’s Disease Biomarkers in People with Mild Cognitive Impairment

Data Availability Statement: All ADNI data are made publicly available upon request.Copyright © 2023 by the authors. Background: Neuropsychiatric symptoms (NPS) are associated with faster decline in mild cognitive impairment (MCI). This study aimed to investigate the association between NPS severity and Alzheimer’s disease (AD) biomarkers, i.e., amyloid-β (Aβ), phosphorylated tau protein (p-tau) and hippocampal volume ratio (HR), to characterise in more detail MCI patients with a poor prognosis. Methods: A total of 506 individuals with MCI and 99 cognitively unimpaired older adults were selected from the ADNI dataset. The patients were divided into three different groups based on their NPI-Q total scores: no NPS (n = 198), mild NPS (n = 160) and severe NPS (n = 148). Regression models were used to assess the association between the severity of NPS and each biomarker level and positivity status. Results: Cerebrospinal fluid Aβ levels were positively associated with older age and lower MMSE scores, while higher p-tau levels were associated with female sex and lower MMSE scores. Only patients with severe NPS had a lower HR (β = −0.18, p = 0.050), i.e., more pronounced medio-temporal atrophy, than those without NPS. Discussion: Only HR was associated with the presence of NPS, partially in line with previous evidence showing that severe NPS may be explained primarily by greater grey matter loss. Future longitudinal studies will be needed to ascertain the relevance of this finding.The data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense, award number W81XWH-12-2-0012). The ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosi-ty; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org (accessed on 10 July 2023)). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. R.M. acknowledges the support received through a research fellowship from the Alzheimer’s Association

Multiple brain networks support processing speed abilities of patients with multiple sclerosis

Objectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes. Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor. Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network. Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS