Neurocognitive assessment and DNA sequencing expand the phenotype and genotype spectrum of Alström syndrome.

Alström syndrome (OMIM#203800) is an ultra-rare autosomal recessive monogenic disease presenting pathogenic variants in ALMS1 (chromosome 2p13). It is characterized by early onset of blindness, hearing loss and systemic comorbidities, with delayed development without cognitive impairment. We aimed to investigate the cognitive functions and describe new pathogenic variants in Alström syndrome patients. Nineteen patients (13 adults, 6 children) underwent a thorough clinical, genetic, laboratory, instrumental, and neurocognitive assessment. Six new pathogenic variants in ALMS1 including the first described in exon 6 were identified. Four patients displayed a "mild phenotype" characterized by slow disease onset or absence of complications, including childhood obesity and association with at least one pathogenic variant in exon 5 or 6. At neurocognitive testing, a significant proportion of patients had deficits in three neurocognitive domains: similarities, phonological memory, and apraxia. In particular, 53% of patients showed difficulties in the auditory working memory test. We found ideomotor and buccofacial apraxia in 74% of patients. "Mild phenotype" patients performed better on auditory working memory and ideomotor apraxia test than "typical phenotype" ones (91.9 + 16.3% vs. 41.7 + 34.5% of correct answers, Z = 64.5, p < .01 and 92.5 + 9.6 vs. 61.7 + 26.3, Z = 61, p < .05, respectively). Deficits in auditory working memory, ideomotor, and buccofacial apraxia were found in these patients and fewer neuropsychological deficits were found in the "mild" phenotype group. Furthermore, in the "mild" phenotype group, it was found that all pathogenic variants are localized before exon 8.

Cumulative semantic cost without successful naming.

Accessing semantic information has negative consequences for successive recovering attempts of similar information. For instance, in the course of picture-naming tasks, the time required to name an object is determined by the total number of items from the same category that have already been named; naming latencies increase proportionally to the total number of semantically related words named previously. This phenomenon is called cumulative semantic cost (or interference). Two picture-naming experiments with children (4-11 years old, 229 participants) investigate whether having successfully named the previous within-category items is a necessary condition for the cumulative semantic cost to appear. We anticipated that younger children would have a larger rate of nonresponses compared with older children, reflecting the fact that younger children have not yet consolidated many lexical representations. Our results confirmed this prediction. Critically, we also observed that cumulative semantic cost was independent of having successfully retrieved previous within-category lexical items. Furthermore, picture trials for which the previous within-category item elicited a nonresponse showed the same amount of cost as those picture trials for which the previous within-category item elicited a correct naming event. Our findings indicate that it is the attempt to retrieve a lexical unit, and not the successful retrieval of a specific lexical unit, that causes semantic cost in picture naming. This cost can be explained by a mechanism of weakening the semantic-to-lexical mappings of semantic coordinate words. The findings are also discussed in the context of retrieval-induced forgetting effects in memory recall research.

Mathematical skills in children with pilocytic astrocytoma.

BACKGROUND: Pediatric patients with circumscribed cerebellar pilocytic astrocytoma (PA) tumors generally perform within the normal range on neuropsychological tests after a complete tumor resection. The outcome in academically relevant abilities such as mathematics, which in adults involve some cerebellar functions, is however much less understood. The aim of this study is to retrospectively investigate the neuroplasticity of mathematical skills and associated cognitive functions following cerebellar resection of PA in pediatric patients. METHODS: Twenty-two children (mean age = 11.2 + 1.8), including 11 PA patients (females = 6) and 11 healthy controls (females = 6), were administered a battery of mathematical (MaT) and neuropsychological tests. Single-case statistical analyses were carried out (Crawford's t) as well as between-group comparisons (Wilcoxon test). Spearman correlations between MaT and neuropsychological tests were calculated. RESULTS: Thirty-six percent of the patients showed difficulties in some mathematical tasks, 50% of them within a broader cognitive deficit. Verbal working memory was associated with MaT performance both in patients and controls while, crucially, visuospatial memory, and visual-motor integration were associated with MaT in patients only. Among patients, MaT correlated negatively with tumor size and positively with the interval surgery test. CONCLUSIONS: The results evince an overall recovery of mathematical abilities despite PA in the majority of patients. This functional reestablishment is supported by visuospatial and visuomotor integration functions that contribute to set up emerging mathematical skills in these patients. Higher levels of compensation are found in more developed tumors as compared to smaller ones.

Global psychological assessment with the evaluation of life and sleep quality and sexual and cognitive function in a large number of patients with acromegaly: a cross-sectional study.

Objective: Acromegaly is associated with somatic disfigurements which impair self-perception of well-being and quality of life. Nowadays, limited data are available on the interplay between hormonal excess and psychological discomfort. The study aimed at investigating the psychological profile, sleep quality, sexual function, cognitive functions, and quality of life in patients with acromegaly. Methods: In 223 acromegaly patients from 5 referral centres, global psychological profile, sleep quality, sexual function, cognitive function, and quality of life were investigated. Results: Depression was found in ~30% of patients, and anxiety in two-thirds, together with severe discomfort in body image mainly in women. Obstructive sleep apnoea syndrome risk and sleep disorders were found in >50% of patients and daily sleepiness in ~20%. Sexual dysfunction was reported in most of the patients, with the most severe impairment in women. Cognitive functions were compromised in ~10% of cases. Disease duration and patient's age and gender were the main determinants of these psychopathological conditions. Depression (P = 0.047), somatic-affective mood lowering (P = 0.021), state (P < 0.001) and trait (P = 0.013) anxiety, and body image distortion in body uneasiness test A (P < 0.001) and B (P = 0.006) were significantly worsened in patients <45 years and slightly worsened in those with disease duration less than 2 years. Male (P < 0.001) and female (P < 0.001) sexual function scores were significantly worsened in patients aged >64 years and slightly worsened in those with disease duration for more than 10 years, particularly in presence of cardiometabolic and respiratory complications. Cognitive symptoms were slightly worsened in older patients and in those with long disease duration. Conclusions: Acromegaly is associated with a relevant impairment of psychological profile persisting despite remission and long-term medical treatment.

Mass is more: The conceiving of (un)countability and its encoding into language in 5-year-old-children.

Is the mass-count distinction merely a linguistic issue, or is it coded in representations other than language? We hypothesized that a difference between mass and count properties should be observed even in absence of linguistic distinctions driven by the morphosyntactic context. We tested 5-6-year-old children's ability to judge sentences with mass nouns (sand), count nouns (ring), and neutral nouns (i.e., those that appear in mass and count contexts with similar frequency; cake). Children refused neutral nouns embedded in uncountable morphosyntactic contexts, showing a preference for a count interpretation. This suggests that linguistic features alone are not sufficient to define the mass-count distinction. Additional analyses showed that children's performance with mass-but not count-morphosyntax correlated with their performance in tasks concerning logical and conservation operations. Altogether, these results suggest that the processing of mass features is not more demanding than count features from a linguistic point of view; rather, mass features entail additional abstraction abilities.