The theory of mind is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the study was to explore the neuropsychological correlates of theory of mind in patients affected by early Parkinson's disease (PD). Thirty-three PD patients and 33 age-, sex-, and education-matched control subjects underwent the Frontal Assessment Battery, as well as tasks assessing "cognitive" and "affective" theory of mind, and memory abilities; questionnaires evaluating behavioral disorders and quality of life were also administrated. Although the 2 groups did not differ on neuropsychological tasks, PD patients' performance on tasks assessing cognitive and affective theory of mind was significantly worse than controls. Moreover, PD patients had more behavioral disorders and worse quality of life than controls. After covarying for behavioral and quality of life scores, the differences between patients and controls on theory of mind tasks remained significant. "Cognitive" theory of mind was associated with Frontal Assessment Battery score and 2 domains of quality of life scale, whereas "affective" theory of mind scores correlated only with behavioral scales such as the Frontal Behavioral Inventory and Apathy Evaluation Scale. The results demonstrate that both affective and cognitive aspects of theory of mind are simultaneously impaired in early PD and suggest that deficits in the 2 subcomponents of theory of mind may be linked to dysfunction of different frontosubcortical circuitries in early PD.

Patients with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) may present anosognosia for their cognitive deficits. Three different methods have been usually used to measure anosognosia in patients with AD and MCI, but no studies have established if they share similar neuroanatomical correlates. The purpose of this study was to investigate if anosognosia scores obtained with the three most commonly used methods to assess anosognosia relate to focal atrophy in AD and MCI patients, in order to improve understanding of the neural basis of anosognosia in dementia. Anosognosia was evaluated in 27 patients (15 MCI and 12 AD) through clinical rating (Clinical Insight Rating Scale, CIRS), patient-informant discrepancy (Anosognosia Questionnaire Dementia, AQ-D), and performance discrepancy on different cognitive domains (self-appraisal discrepancies, SADs). Voxel-based morphometry correlational analyses were performed on magnetic resonance imaging (MRI) data with each anosognosia score. Increasing anosognosia on any anosognosia measurement (CIRS, AQ-D, SADs) was associated with increasing gray matter atrophy in the medial temporal lobe including the right hippocampus. Our results support a unitary mechanism of anosognosia in AD and MCI, in which medial temporal lobes play a key role, irrespectively of the assessment method used. This is in accordance with models suggesting that anosognosia in AD is primarily caused by a decline in mnemonic processes.

The use of brief neuropsychological tests leads to a more accurate CFS assessment in two-thirds of MS patients, and a more accurate EDSS calculation in 25% of patients with a score ⩽4.0. This may help clinicians to better recognize cognitive impairment in everyday clinical practice, especially in the case of isolated cognitive worsening.

The aim of the present study was to verify whether duration, order and space representations share common mechanisms. A two-alternative time estimation paradigm was implemented in two experiments in which subjects had to judge whether the first or the second tone in a pair was shorter (or longer) and to respond by pressing a left or a right key. In Experiment 1, subjects were more accurate in conditions where the first tone was shorter or the second tone was longer, with no effects of spatial information. In Experiment 2, a modification of the paradigm allowed us to demonstrate the presence of a SNARC-like effect, as evidenced by the interaction between order and response key, and of a second-order interaction among duration, order and space. These findings seem consistent with the hypothesis that processing of these three mental categories is subserved by a common mechanism, representing duration and order information according to a spatially-defined magnitude system.

Differently from the adult multiple sclerosis (MS) population, the predictive value of cognitive impairment in early-onset MS is still unknown. We aim to evaluate whether cognitive performances at disease onset predict disease progression in young people with MS. This is a retrospective study on early onset (<25 years) MS patients, who had a baseline cognitive evaluation at disease onset. Demographic and longitudinal clinical data were collected up to 7 years follow up. Cognitive abilities were assessed at baseline through the Brief Repeatable Battery. Associations between cognitive abilities and clinical outcomes (occurrence of a relapse, and 1-point EDSS progression) were evaluated with stepwise logistic and Cox regression models. We included 51 patients (26 females), with a mean age at MS onset of 17.2 ± 3.9 years, and an EDSS of 2.5 (1.0–6.0). Over the follow-up, twenty-five patients had at least one relapse, and 7 patients had 1-point EDSS progression. Relapse occurrence was associated with lower 10/36 SPART scores (HR = 0.92; p = 0.002) and higher WLG scores (HR = 1.05; p = 0.01). EDSS progression was associated with lower SDMT score (OR: 0.70; p = 0.04). Worse visual memory and attention/information processing were associated with relapses and with increased motor disability after up to 7-years follow-up. Therefor, specific cognitive subdomains might better predict clinical outcomes than the overall cognitive impairment in early-onset MS.

BackgroundInherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes.MethodsAn integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction.ResultsThis study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function.ConclusionThis study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

Abstract. Apathy is defined as a lack of motivation and has been reported to be common in Alzheimer's disease (AD) and Parkinson's disease (PD). To explore the neuropsychological correlates of apathy in patients with PD related dementia (PDD) and AD and to identify the specific cognitive profile of apathy in the two forms of neurodegenerative disease, 61 non-depressed patients (29 PDD and 32 AD) were selected. Out of these, 29 patients (47.5%) were detected as apathetic (14 PDD-A+ and 15 AD-A+), and 32 patients as non-apathetic (15 PDD-A-and 17 AD-A-). All patients underwent cognitive tasks tapping memory, visuospatial and executive functions, behavioral rating scales and Clinical Judgment for Apathy Syndrome (CJ-AS), an inventory developed to measure severity of apathy. The four subgroups differed significantly on memory and frontal tasks. The PDD-A+ performed significantly worse than PDD-Aon frontal tasks. The AD-A+ had poorer performance than AD-A-on frontal tasks. Last, PDD-A+ achieved significantly higher scores than AD-A+ on memory tasks. The four groups differed significantly on CJ-AS and behavioral rating scales. The results showed that apathetic patients with both forms of dementia showed a common neuropsychological and behavioral picture, characterized by defects on frontal tasks, thus strongly supporting the existence of an 'apathetic syndrome', characterized by specific cognitive and psychological symptoms.

Background: Few studies examined the effects of combined motor and cognitive rehabilitation in patients with multiple sclerosis (MS). The present prospective, multicenter, observational study aimed to determine the efficacy of an integrated cognitive and neuromotor rehabilitation program versus a traditional neuromotor training on walking, balance, cognition and emotional functioning in MS patients.Methods: Sixty three MS patients were selected and assigned either to the Integrated Treatment Group (ITG; n = 32), receiving neuropsychological treatment (performed by ERICA software and paper–pencil tasks) complemented by conventional neuromotor rehabilitation, or to the Motor Treatment Group (n = 31) receiving neuromotor rehabilitation only. The intervention included two 60-min sessions per week for 24 weeks. At baseline and at end of the training all patients underwent a wide-range neuropsychological, psychological/emotional, and motor assessment.Results: At baseline the two groups did not differ for demographic, neuropsychological, psychological/emotional, and motor features significantly. After rehabilitation, only ITG group significantly (p-corrected for False Discovery Rate) improved on test tapping spatial memory, attention and cognitive flexibility, as well as on scales assessing depression and motor performance (balance and gait). A regression analysis showed that neuropsychological and motor improvement was not related to improvements in fatigue and depression.Conclusion: The present study demonstrated positive effects in emotional, motor, and cognitive aspects in MS patients who received an integrated cognitive and neuromotor training. Overall, results are supportive of interventions combining motor and cognitive training for MS.