Search Results (35)

Background/Objectives: Hereditary spastic paraplegias (HSPs) comprise a heterogenous spectrum of rare neurogenetic disorders predominantly characterized by progressive spasticity and weakness of the lower extremities. Among autosomal-dominant forms of HSP, molecular defects in the SPAST gene—particularly those associated with the SPG4 subtype—represent the most frequent genetic cause. SPAST encodes spastin, a microtubule-severing ATPase, crucial for cytoskeletal remodeling, neuronal connectivity, and intracellular trafficking. Disruption of spastin function can impair neurite outgrowth and synaptic formation, processes increasingly implicated in neurodevelopmental disorders (NDDs). Methods: We conducted a comprehensive clinical, neurological, and dysmorphological evaluation of a 4-year-old male. Standardized neuropsychological assessments were administered. Whole-exome sequencing (WES) was performed to identify underlying genetic causes. EEG and 3T-brain MRI were also acquired. Results: The proband harbored two novel de novo heterozygous missense variants in cis of the SPAST gene, displaying the typical features of early-onset and complex HSP, in addition to global developmental delay and severe autism spectrum disorder (ASD), an underexplored manifestation in this rare genetic disorder. Conclusions: These findings broaden the clinical and mutational spectrum of SPG4, underscoring the importance of considering SPAST gene analysis in patients with ASD in the early years of life and early motor delay, even in the presence of only subtle pyramidal signs. We advocate for comprehensive neuropsychiatric assessment in the diagnostic pathway of early-onset complex HSP presentations and support further investigation into the role of spastin in neuronal connectivity. Full article

Background: Cognitive heterogeneity in Parkinson’s disease (PD) remains a diagnostic and prognostic challenge, particularly in early stages. In this cross-sectional study, we aimed to identify clinically relevant cognitive subtypes in early PD by integrating neuropsychological profiles with regional brain atrophy assessed via visual MRI scales. Methods: Eighty-one de novo PD patients (≤36 months from diagnosis) and twenty healthy controls underwent 3T MRI with visual atrophy ratings and completed an extensive neuropsychological battery. Results: Using a mixed a priori–a posteriori approach, we defined eight anatomocognitive subtypes reflecting distinct patterns of regional vulnerability: frontosubcortical, posterior cortical, left/right hippocampal, global, and preserved cognition. Specific MRI markers correlated with cognitive deficits in executive, visuospatial, memory, and language domains. Cluster analyses supported subtype validity (AUC range: 0.68–0.95). Conclusions: These results support a practical classification model linking cognitive performance to brain structural changes in early PD. This scalable approach may improve early patient stratification and guide personalized management strategies. Longitudinal studies are needed to assess progression patterns and therapeutic implications. Full article

Background and Objectives: Theory of mind (ToM) deficits in children with ADHD are closely related to social difficulties and problems in interpersonal interactions. Evidence suggests that these cognitive deficits negatively affect the ability to understand and respond to others’ emotions and intentions, thus contributing to social isolation and a lower quality of life. However, the findings across studies vary, indicating that ADHD subtype and comorbidities, such as anxiety and mood disorders, can significantly influence sociocognitive deficits, modulating the extent of social problems. Materials and Methods: This review examines the relationship among ADHD, ToM, and empathy, analyzing studies comparing children with ADHD with peers with typical development or other neurodevelopmental conditions. A search in PubMed, Scopus, and the Cochrane Library prior to January 10, without time restrictions, using “ADHD”, “Cognitive Empathy”, and “Theory of Mind” identified relevant studies assessing these abilities through neuropsychological tests or questionnaires. Results: Of the initial 243 studies, 23 studies met the inclusion criteria. Children with ADHD exhibited significant impairments in ToM and empathy, affecting social cognition and interpersonal understanding. Various assessment tools revealed difficulties in understanding beliefs, emotions, and intentions, with executive function deficits playing a crucial role in shaping these social challenges. Conclusions: This review highlights the need for targeted therapeutic interventions that not only address cognitive deficits but consider emotional and metacognitive aspects, such as emotion regulation and self-awareness. Future research should focus on integrating executive function training with approaches that develop metacognitive and emotional skills, thus providing more comprehensive support. Full article

Background-objectives: Multiple dynamic interacting factors contribute to the presence and progression of eating disorders (ED). Empirical research has provided mixed findings regarding the mechanisms explaining the contribution of body mass index (BMI) to the diverse ED endophenotypes. The present study aims to evaluate the underlying processes (direct and indirect effects) contributing to BMI and ED severity, considering the contribution of multiple neuropsychological constructs. Method: Path analysis, implemented through structural equation models (SEM), was applied to a sample of N = 193 ED patients, men and women, aged 17 to 50 years old, and diagnosed with bulimia nervosa, night eating syndrome, binge eating disorder, and other specified feeding. Results: BMI was directly associated with ED severity level. The ED symptom level was also a mediational link into the relationship between BMI with emotion regulation strategies, decision-making capacity, stress levels, and impulsiveness. Multigroup SEM revealed invariance of the structural coefficients by sex, but differences according to the ED subtype. Conclusions: This study provides new empirical evidence on predictors of ED severity, focusing on the role of impaired decision-making and BMI. Our results could contribute to new intervention plans with techniques specifically aimed at improving emotional regulation capacity, decreasing impulsivity levels, and improving reasoning skills. Nutrition education plans may also play a key role for preventing the onset and progression of ED, helping patients understand how food affects their physical and emotional health and how to manage anxiety and fears related to food. Full article

Background/Objectives: This systematic review of neuropsychological rehabilitation strategies for primary progressive aphasia will consider recent developments in cognitive neuroscience, especially neuroimaging techniques such as EEG and fMRI, to outline how these tools might be integrated into clinical practice to maximize treatment outcomes. Methods: A systematic search of peer-reviewed literature from the last decade was performed following the PRISMA guidelines across multiple databases. A total of 63 studies were included, guided by predefined inclusion and exclusion criteria, with a focus on cognitive and language rehabilitation in PPA, interventions guided by neuroimaging, and mechanisms of neuroplasticity. Results: Integration of neuroimaging techniques contributes to the increase in the efficacy of interventions with critical information about the neural mechanisms underlying language deficits in the aphasias. Traditional rehabilitation strategies, technology-assisted interventions, and non-invasive brain stimulation techniques hold considerable promise for language improvement. Neuroimaging was also found to be necessary in subtype-specific differentiation toward tailoring therapeutic intervention. Evidence also shows that directed and sustained interventions using neuroplasticity can have long-term effects in managing the symptoms of PPA. Conclusions: The present review underlines the necessity of including cognitive neuroscience techniques within neuropsychological rehabilitation to enhance therapeutic outcomes in PPA. In addition, neuroimaging modalities such as EEG and fMRI are also of great importance in understanding the underlying neurobiology of language disturbances and guiding tailored interventions. Long-term benefits of these approaches should be evaluated, including their applicability in routine clinical practice. Full article

Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer’s disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols. Full article

Cerebellar neurodegenerative ataxias are a group of disorders affecting the cerebellum and its pathways with different neurological structures. Transcranial sonography (TCS) has been used for the evaluation of brain parenchymal structures in various diseases because of its fast and safe utilization, especially in neuropsychiatric and neurodegenerative diseases. The aim of our study was to investigate TCS characteristics of patients with neurodegenerative cerebellar ataxias. In our study, we included 74 patients with cerebellar degenerative ataxia; 36.5% had autosomal dominant onset, while 33.8% had sporadic onset. Standardized ultrasonographic planes were used for the identification of brain structures of interest. The SARA, INAS, neuropsychological and psychiatric scales were used for the further clinical evaluation of our study participants. The brainstem raphe was discontinued in 33.8% of the patients. The substantia nigra (SN) hyperechogenicity was identified in 79.7%. The third and fourth ventricle enlargement had 79.7% and 45.9% of patients, respectively. A positive and statistically significant correlation was found between SN hyperechogenicity with dystonia (p < 0.01), rigidity and dyskinesia (p < 0.05). The higher SARA total score is statistically significantly correlated with the larger diameter of the III (r = 0.373; p = 0.001) and IV ventricles (r = 0.324; p = 0.005). In such patients, the echogenicity of substantia nigra has been linked to extrapyramidal signs, and raphe discontinuity to depression. Furthermore, ataxia and its clinical subtypes have positively correlated with the IV ventricle diameter, indicating brain atrophy and brain mass reduction. Full article

This study reports on several specific neurocognitive processes and eye-tracking predictors of reading outcomes for a sample of children with Developmental Dyslexia (DD) and At-tention-Deficit/Hyperactivity Disorder – inattentive subtype (ADHD-I) compared to typical readers. Participants included 19 typical readers, 21 children diagnosed with ADHD-I and 19 children with DD. All participants were attending 4th grade and had a mean age of 9.08 years. The psycholinguistic profile of each group was assessed using a battery of neuropsy-chological and linguistic tests. Participants were submitted to a silent reading task with lex-ical manipulation of the text. Multinomial logistic regression was conducted to evaluate the predictive capability of developing dyslexia or ADHD-I based on the following measures: (a) a linguistic model that included measures of phonological awareness, rapid naming, and reading fluency and accuracy; (b) a cognitive neuropsychological model that included measures of memory, attention, visual processes, and cognitive or intellectual functioning, and (c) an additive model of lexical word properties with manipulation of word-frequency and word-length effects through eye-tracking. The additive model in conjunction with the neuropsychological model classification improved the prediction of who develops dyslexia or ADHD-I having as baseline normal readers. Several of the neuropsychological and eye-tracking variables have power to predict the degree of reading outcomes in children with learning disabilities. Full article

This study aimed to elucidate the long-term progression of mild cognitive impairment (MCI) within a comprehensive longitudinal dataset, distinguish it from healthy aging, explore the influence of a dementia subtype on this progression, and identify potential contributing factors. Patients with prodromal and preclinical cases underwent regular neuropsychological assessments utilizing various tools. The study included a total of 140 participants with MCI, categorized into Alzheimer’s disease (AD) and non-AD subtypes. Our dataset revealed an overall progression rate of 92.8% from MCI to the clinical stage of dementia during the follow-up period, with an annual rate of 15.7%. Notably, all prodromal cases of Lewy body dementia/Parkinson’s disease (LBD/PDD) and frontotemporal dementia (FTD) advanced to clinical stages, whereas 7% of vascular dementia (VaD) cases and 8.4% of AD cases remained in the prodromal stage throughout follow-up. Furthermore, we observed a faster progression rate in MCI-AD cases compared to non-AD sufferers (53.9% vs. 35.5%, Entropy: 0.850). This study revealed significant cognitive changes in individuals with MCI over time. The mini-mental state examination (MMSE), global deterioration scale (GDS), and calculation tests were the most effective tests for evaluation of MCI. These findings may offer valuable insights for the development of personalized interventions and management strategies for individuals with MCI. Full article

In the brain, the extracellular matrix (ECM) composition shapes the neuronal microenvironment and can undergo substantial changes with cerebral pathology. Brevican is integral to the formation of the ECM’s neuroprotective perineuronal nets (PNNs). Decreased brevican levels were reported in vascular dementia (VaD) but not in Alzheimer’s disease (AD). However, the status of brevican in clinical cohorts with high concomitance of AD pathological burden and cerebrovascular disease (CeVD) is unclear. In this study, 32 non-cognitively impaired (NCI), 97 cognitively impaired no dementia (CIND), 46 AD, and 23 VaD participants recruited from memory clinics based in Singapore underwent neuropsychological and neuroimaging assessments, together with measurements of serum brevican. Association analyses were performed between serum brevican and neuroimaging measures of CeVDs, including white matter hyperintensities (WMHs), lacunes, cortical infarcts, and cerebral microbleeds. Using an aggregated score for CeVD burden, only CIND participants showed lower brevican levels with higher CeVD compared to those with lower CeVD burden (p = 0.006). Among the CeVD subtypes assessed, only elevated WMH burden was associated with lower brevican levels (OR = 2.7; 95% CI = 1.3–5.5). Our findings suggest that brevican deficits may play a role in early cerebrovascular damage in participants at risk of developing dementia. Full article

Fibromyalgia (FM) is a condition characterized by musculoskeletal pain and multiple comorbidities. Our study aimed to identify four clusters of FM patients according to their core clinical symptoms and neuropsychological comorbidities to identify possible therapeutic targets in the condition. We performed a population-based cohort study on 251 adult FM patients referred to primary care according to the 2010 ACR case criteria. Patients were aggregated in clusters by a K-medians hierarchical cluster analysis based on physical and emotional symptoms and neuropsychological variables. Four different clusters were identified in the FM population. Global cluster analysis reported a four-cluster profile (cluster 1: pain, fatigue, poorer sleep quality, stiffness, anxiety/depression and disability at work; cluster 2: injustice, catastrophizing, positive affect and negative affect; cluster 3: mindfulness and acceptance; and cluster 4: surrender). The second analysis on clinical symptoms revealed three distinct subgroups (cluster 1: fatigue, poorer sleep quality, stiffness and difficulties at work; cluster 2: pain; and cluster 3: anxiety and depression). The third analysis of neuropsychological variables provided two opposed subgroups (cluster 1: those with high scores in surrender, injustice, catastrophizing and negative affect, and cluster 2: those with high scores in acceptance, positive affect and mindfulness). These empirical results support models that assume an interaction between neurobiological, psychological and social factors beyond the classical biomedical model. A detailed assessment of such risk and protective factors is critical to differentiate FM subtypes, allowing for further identification of their specific needs and designing tailored personalized therapeutic interventions. Full article

ADHD is a neurodevelopmental disorder appearing in childhood but remaining in many cases in adults. There are both pharmacological and non-pharmacological approaches to treating ADHD, but they do not have the same efficacy in all subjects. Better knowledge of the neurophysiological basis of this disorder will allow for the design of more effective treatments. Studies performing qEEG analysis in children suggest the existence of subgroups of ADHD patients with different neurophysiological traits. There are fewer studies in adults, who might have undergone plastic changes allowing them to cope with ADHD symptoms along with brain maturation. Herein, we study cognitive performance and the theta/beta ratio in young adults with ADHD symptoms. We found that subjects with ADHD symptoms and low working memory performance (n = 30) present higher theta/beta ratios than controls (n = 40) at O2 and T6 in the eyes-closed condition, as well as a tendency toward a higher theta/beta ratio at O1 and Cz. Subjects with ADHD and high working memory performance (n = 50) do not differ from the controls in their theta/beta ratios at any derivation. Our results suggest that neuropsychological profiling could be useful for patient subgrouping. Further research will allow for the distinction of neuropsychological profiles and their neurophysiological correlates, leading to a better classification of ADHD subtypes, thus improving treatment selection. Full article

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient’s initial classification. Full article

The aim of this study was to explore, in a sample of patients with a diagnosis of AN, the ability to question their first impression and, in particular, the willingness to integrate their prior ideas and thoughts with additional progressive incoming information. A total of 45 healthy women and 103 patients with a diagnosis of AN, consecutively admitted to the Eating Disorder Padova Hospital–University Unit, underwent a broad clinical and neuropsychological assessment. All participants were administered the Bias Against Disconfirmatory Evidence (BADE) task, which specifically investigates belief integration cognitive bias. Acute AN patients showed a significantly greater bias toward disconfirming their previous judgment, in comparison to healthy women (BADE score, respectively, 2.5 ± 2.0 vs. 3.3 ± 1.6; Mann–Whitney test, p = 0.012). A binge-eating/purging subtype of AN individuals, compared to restrictive AN patients and controls, showed greater disconfirmatory bias and also a significant propensity to uncritically accept implausible interpretations (BADE score, respectively, 1.55 ± 1.6 and 2.70 ± 1.97 vs. 3.33 ± 1.63; Kruskal–Wallis test, p = 0.002 and liberal acceptance score, respectively, 1.32 ± 0.93 and 0.92 ± 1.21 vs. 0.98 ± 0.75; Kruskal–Wallis test p = 0.03). Abstract thinking skills and cognitive flexibility, as well as high central coherence, are neuropsychological aspects positively correlated with cognitive bias, in both patients and controls. Research into belief integration bias in AN population could enable us to shed light on hidden dimensional aspects, facilitating a better understanding of the psychopathology of a disorder that is so complex and difficult to treat. Full article

Developmental dyslexia can be viewed as the result of the effects of single deficits or multiple deficits. This study presents a test of the applicability of a multifactor-interactive model (MFi-M) with a preliminary set of five variables corresponding to different neuropsychological functions involved in the reading process. The model has been tested on a sample of 55 school-age children with developmental dyslexia. The results show that the data fit a model in which each variable contributes to the reading ability in a non-additive but rather interactive way. These findings constitute a preliminary validation of the plausibility of the MFi-M, and encourage further research to add relevant factors and specify their relative weights. It is further discussed how subtype-based intervention approaches can be a suitable and advantageous framework for clinical intervention in a MFi-M perspective. Full article