Validity, diagnostics and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

BACKGROUND: This study is aimed at assessing the clinimetric properties and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in patients with Huntington's disease (HD). METHODS: N = 39 motor-manifest HD patients, N = 74 Parkinson's disease (PD) patients and N = 92 matched HCs were administered the MoCA. HD patients further underwent the Unified Huntington's Disease Rating Scale (UHDRS), self-report questionnaires for anxiety and depression and a battery of first- and second-level cognitive tests. Construct validity was tested against cognitive and behavioural/psychiatric measures, whereas ecological validity against motor-functional subscales of the UHDRS. Sensitivity to disease severity was tested, via a logistic regression, by exploring whether the MoCA discriminated between patients in Shoulson-Fahn stage ≤ 2 vs. > 2. The same analysis was employed to test its ability to discriminate HD patients from HCs and PD patients. RESULTS: The MoCA converged towards cognitive and behavioural measures but diverged from psychiatric ones, being also associated with motor/functional measures from the UHDRS. In identifying patients with cognitive impairment, adjusted MoCA scores were highly accurate (AUC = .92), yielding optimal diagnostics at the cut-off of < 19.945 (J = .78). The MoCA was able to discriminate patients in the middle-to-advanced from those in the early-to-middle stages of the disease (p = .037), as well as to differentiate HD patients from both HCs (p < .001) and PD patients (p < .001). CONCLUSIONS: The MoCA is a valid, diagnostically sound and feasible cognitive screener in motor-manifest HD patients, whose adoption is thus encouraged in clinical practice and research.

Economic burden of Huntington disease in Europe and the USA: Results from the Huntington's Disease Burden of Illness study.

BACKGROUND AND PURPOSE: The prevalence of Huntington disease (HD) has increased over time; however, there is a lack of up-to-date evidence documenting the economic burden of HD by disease stage. This study provides an estimate of the annual direct medical, nonmedical, and indirect costs associated with HD from participants in the Huntington's Disease Burden of Illness (HDBOI) study in five European countries and the USA. METHODS: The HDBOI is a retrospective, cross-sectional study. Data collection was conducted between September 2020 and May 2021. Participants were recruited by their HD-treating physicians and categorized as early stage (ES), mid stage (MS), or advanced stage (AS) HD. Data were collected via three questionnaires: a case report form, completed by physicians who collected health care resource use associated with HD to compute direct medical cost, and optional patient and caregiver questionnaires, which included information used to compute nondirect medical and indirect costs. Country-specific unit cost sources were used. RESULTS: HDBOI cost estimates were €12,663 (n = 2094) for direct medical costs, €2984 (n = 359) for nondirect medical costs, and €47,576 (n = 436) for indirect costs. Costs are higher in patients who are at later stages of disease; for example, direct medical costs estimates were €9220 (n = 846), €11,885 (n = 701), and €18,985 (n = 547) for ES, MS, and AS, respectively. Similar trends were observed for nondirect and indirect costs. Costs show large variations between patients and countries. CONCLUSIONS: Cost estimates from the HDBOI study show that people with HD and their caregivers bear a large economic burden that increases as disease progresses.

Polyglutamine tracts regulate beclin 1-dependent autophagy.

Nine neurodegenerative diseases are caused by expanded polyglutamine (polyQ) tracts in different proteins, such as huntingtin in Huntington's disease and ataxin 3 in spinocerebellar ataxia type 3 (SCA3). Age at onset of disease decreases with increasing polyglutamine length in these proteins and the normal length also varies. PolyQ expansions drive pathogenesis in these diseases, as isolated polyQ tracts are toxic, and an N-terminal huntingtin fragment comprising exon 1, which occurs in vivo as a result of alternative splicing, causes toxicity. Although such mutant proteins are prone to aggregation, toxicity is also associated with soluble forms of the proteins. The function of the polyQ tracts in many normal cytoplasmic proteins is unclear. One such protein is the deubiquitinating enzyme ataxin 3 (refs 7, 8), which is widely expressed in the brain. Here we show that the polyQ domain enables wild-type ataxin 3 to interact with beclin 1, a key initiator of autophagy. This interaction allows the deubiquitinase activity of ataxin 3 to protect beclin 1 from proteasome-mediated degradation and thereby enables autophagy. Starvation-induced autophagy, which is regulated by beclin 1, was particularly inhibited in ataxin-3-depleted human cell lines and mouse primary neurons, and in vivo in mice. This activity of ataxin 3 and its polyQ-mediated interaction with beclin 1 was competed for by other soluble proteins with polyQ tracts in a length-dependent fashion. This competition resulted in impairment of starvation-induced autophagy in cells expressing mutant huntingtin exon 1, and this impairment was recapitulated in the brains of a mouse model of Huntington's disease and in cells from patients. A similar phenomenon was also seen with other polyQ disease proteins, including mutant ataxin 3 itself. Our data thus describe a specific function for a wild-type polyQ tract that is abrogated by a competing longer polyQ mutation in a disease protein, and identify a deleterious function of such mutations distinct from their propensity to aggregate.

The validation of the Italian version of multiple sclerosis neuropsychological screening questionnaire in Huntington's disease.

INTRODUCTION: Multiple sclerosis neuropsychological questionnaire (MSNQ) is a brief questionnaire useful for screening patient's and informant's self-perception of cognitive dysfunctions in daily life activities. Our study aims to evaluate the MSNQ validity in Huntington's disease (HD) mutation carriers and to correlate MSNQ scores with neurological, cognitive, and behavioral variables. METHODS: The study was conducted on a sample of 107 subjects from presymptomatic to the middle stage of HD recruited at LIRH Foundation and C.S.S. Mendel Institute in Rome. Unified Huntington's Disease Rating Scale (UHDRS), an internationally standardized and validated scale, was used to evaluate motor, functional cognitive, and behavioral domains. RESULTS: Our results showed that in HD subjects, MSNQ has a unidimensional factor structure. Correlational analyses indicated a good correlation between the MSNQ-patient version (MSNQ-p) and clinical variables, specifically with cognitive dysfunction and behavioral alterations. Moreover, higher scores in MSNQ-p were associated with higher motor disease and functional impairment showing that patients in advanced stage of HD perceive a greater cognitive impairment. These results confirm the questionnaire's reliability. CONCLUSIONS: The present study demonstrates the validity and adaptability of MSNQ in the HD population proposing it as a cognitive tool during routine clinical follow-ups, although further research is needed to determine an optimal cut-off score for this measure.

A Comprehensive Haplotype-Targeting Strategy for Allele-Specific HTT Suppression in Huntington Disease.

Huntington disease (HD) is a fatal neurodegenerative disorder caused by a gain-of-function mutation in HTT. Suppression of mutant HTT has emerged as a leading therapeutic strategy for HD, with allele-selective approaches targeting HTT SNPs now in clinical trials. Haplotypes associated with the HD mutation (A1, A2, A3a) represent panels of allele-specific gene silencing targets for efficient treatment of individuals with HD of Northern European and indigenous South American ancestry. Here we extend comprehensive haplotype analysis of the HD mutation to key populations of Southern European, South Asian, Middle Eastern, and admixed African ancestry. In each of these populations, the HD mutation occurs predominantly on the A2 HTT haplotype. Analysis of HD haplotypes across all affected population groups enables rational selection of candidate target SNPs for development of allele-selective gene silencing therapeutics worldwide. Targeting SNPs on the A1 and A2 haplotypes in parallel is essential to achieve treatment of the most HD-affected subjects in populations where HD is most prevalent. Current allele-specific approaches will leave a majority of individuals with HD untreated in populations where the HD mutation occurs most frequently on the A2 haplotype. We further demonstrate preclinical development of potent and selective ASOs targeting SNPs on the A2 HTT haplotype, representing an allele-specific treatment strategy for these individuals. On the basis of comprehensive haplotype analysis, we show the maximum proportion of HD-affected subjects that may be treated with three or four allele targets in different populations worldwide, informing current allele-specific HTT silencing strategies.

Length of Uninterrupted CAG, Independent of Polyglutamine Size, Results in Increased Somatic Instability, Hastening Onset of Huntington Disease.

Huntington disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Although the length of this repeat is inversely correlated with age of onset (AOO), it does not fully explain the variability in AOO. We assessed the sequence downstream of the CAG repeat in HTT [reference: (CAG)n-CAA-CAG], since variants within this region have been previously described, but no study of AOO has been performed. These analyses identified a variant that results in complete loss of interrupting (LOI) adenine nucleotides in this region [(CAG)n-CAG-CAG]. Analysis of multiple HD pedigrees showed that this LOI variant is associated with dramatically earlier AOO (average of 25 years) despite the same polyglutamine length as in individuals with the interrupting penultimate CAA codon. This LOI allele is particularly frequent in persons with reduced penetrance alleles who manifest with HD and increases the likelihood of presenting clinically with HD with a CAG of 36-39 repeats. Further, we show that the LOI variant is associated with increased somatic repeat instability, highlighting this as a significant driver of this effect. These findings indicate that the number of uninterrupted CAG repeats, which is lengthened by the LOI, is the most significant contributor to AOO of HD and is more significant than polyglutamine length, which is not altered in these individuals. In addition, we identified another variant in this region, where the CAA-CAG sequence is duplicated, which was associated with later AOO. Identification of these cis-acting modifiers have potentially important implications for genetic counselling in HD-affected families.

Modeling Manifest Huntington's Disease Prevalence Using Diagnosed Incidence and Survival Time.

INTRODUCTION: Understanding the epidemiology of Huntington's disease (HD) is key to assessing disease burden and the healthcare resources required to meet patients' needs. We aimed to develop and validate a model to estimate the diagnosed prevalence of manifest HD by the Shoulson-Fahn stage. METHODS: A literature review identified epidemiological data from Brazil, Canada, France, Germany, Italy, Spain, the UK, and the USA. Data on staging distribution at diagnosis, progression, and mortality were derived from Enroll-HD. Newly diagnosed patients with manifest HD were simulated by applying annual diagnosed incidence rates to the total population in each country, each year from 1950 onwards. The number of diagnosed prevalent patients from the previous year who remained in each stage was estimated in line with the probability of death or progression. Diagnosed prevalence in 2020 was estimated as the sum of simulated patients, from all the incident cohorts, still alive. RESULTS: The model estimates that in 2020, there were 66,787 individuals diagnosed with HD in the 8 included countries, of whom 62-63% were in Shoulson-Fahn stages 1 and 2 (with less severely limited functional capacity than those in stages 3-5). Diagnosed prevalence is estimated to be 8.2-9.0 per 100,000 in the USA, Canada, and the 5 included European countries and 3.5 per 100,000 in Brazil. CONCLUSION: The modeled estimates generally accord with the previously published data. This analysis contributes to better understanding of the epidemiology of HD and highlights areas of uncertainty.

Abnormal visual scanning and impaired mental state recognition in pre-manifest Huntington disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder that affects not only the motor but also the cognitive and the neuropsychiatric domain. In particular, deficits in mental state recognition may emerge already at early pre-manifest stages of the disease. The aim of this research was to explore the relation between visual scanning behavior and complex mental state recognition in individuals with pre-manifest HD (preHD). Eighteen preHD and eighteen age- and gender-matched healthy controls took the revised "Reading the Mind in the Eyes" test while their eye-movements were tracked. In addition to the expected deficits in mental state recognition, preHD showed abnormalities concerning all three scanning variables we considered, namely the absolute number of fixations (FC), the average fixation duration (AFD), and the percentage of time spent fixating (FTR). In preHD, FC and FTR but not AFD predicted mental state recognition over and beyond general disease-related declines in cognition and motor functioning. Notably, preHD showed abnormal vertical and horizontal fixation patterns, and these patterns predicted mental state recognition, suggesting the involvement of mechanisms related to the embodied processing of emotional stimuli. Overall, our results suggest that impaired facial mental state recognition in pre-manifest HD is partly due to emotional-motivational factors affecting the visual scanning of facial expressions.

Validity of the Italian multiple sclerosis neuropsychological screening questionnaire.

The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is a brief questionnaire useful for screening patients with multiple sclerosis (MS) at risk for cognitive impairment. It includes a patient self-assessment (MSNQ-p) and a section for the caregiver (informant) (MSNQ-i). This study's aim was to validate the Italian version of MSNQ and to compare MSNQ scores with Symbol Digit Modality Test (SDMT), Beck Depression Inventory (BDI), and Expanded Disability Status Scale (EDSS) score, measuring cognitive skills, mood status, and physical disability respectively. We enrolled 122 MS patients (and related caregivers) at MS center of Tor Vergata University Hospital of Rome. The final study sample consisted of 122 patients with MS (90 relapsing-remitting, 24 secondary progressive, and 8 primary progressive). Our results highlighted that MSNQ has a unidimensional factor structure. Correlational analyses found a good correlation between both versions (MSNQ-p and MSNQ-i) of the questionnaire. Both MSNQ-p and MSNQ-i were correlated with clinical variables, specifically with cognitive impairment, mood disorder, and with disability. The Italian version of MSNQ is reliable and useful as screening tool to identify MS patients at high risk of cognitive impairment.

Compensating for verbal-motor deficits in neuropsychological assessment in movement disorders: sensitivity and specificity of the ECAS in Parkinson's and Huntington's diseases.

INTRODUCTION: The study aims at investigating psychometric properties of the Edinburgh cognitive and behavioural ALS screen (ECAS) in Parkinson's (PD) and Huntington's (HD) diseases. The sensitivity and specificity of the ECAS in highlighting HD and PD cognitive-behavioural features and in differentiating between these two populations and from healthy controls (HC) were evaluated. Moreover, correlations between the ECAS and traditional cognitive measures, together with core clinical features, were analysed. METHODS: Seventy-three PD patients, 38 HD patients, and 49 education-matched healthy participants were enrolled. Participants were administered the ECAS, together with other cognitive screening tools and psychological questionnaires. Patients' behavioural assessment was also carried out with carers. RESULTS: The ECAS distinguished between HD patients and HC and between the two clinical syndromes with high sensitivity and specificity. Even if the diagnostic accuracy of the ECAS in distinguishing between PD and HC was low, the PD cognitive phenotype was very well described by the ECAS performances. Convergent validity of the ECAS against other traditional cognitive screening was observed, as well as correlations with psychological aspects and typical clinical features, especially for the HD group. CONCLUSIONS: The ECAS represents a rapid and feasible tool, useful also in other neurodegenerative disorders affecting verbal-motor abilities than the amyotrophic lateral sclerosis such as PD and HD. Clinical applications in these neurodegenerative conditions require further investigations and, probably, some adaptations of the original test.

A Novel Triplet-Primed PCR Assay to Detect the Full Range of Trinucleotide CAG Repeats in the Huntingtin Gene (HTT).

The expanded CAG repeat number in HTT gene causes Huntington disease (HD), which is a severe, dominant neurodegenerative illness. The accurate determination of the expanded allele size is crucial to confirm the genetic status in symptomatic and presymptomatic at-risk subjects and avoid genetic polymorphism-related false-negative diagnoses. Precise CAG repeat number determination is critical to discriminate the cutoff between unexpanded and intermediate mutable alleles (IAs, 27-35 CAG) as well as between IAs and pathological, low-penetrance alleles (i.e., 36-39 CAG repeats), and it is also critical to detect large repeat expansions causing pediatric HD variants. We analyzed the HTT-CAG repeat number of 14 DNA reference materials and of a DNA collection of 43 additional samples carrying unexpanded, IAs, low and complete penetrance alleles, including large (>60 repeats) and very large (>100 repeats) expansions using a novel triplet-primed PCR-based assay, the AmplideX PCR/CE HTT Kit. The results demonstrate that the method accurately genotypes both normal and expanded HTT-CAG repeat numbers and reveals previously undisclosed and very large CAG expansions >200 repeats. We also show that this technique can improve genetic test reliability and accuracy by detecting CAG expansions in samples with sequence variations within or adjacent to the repeat tract that cause allele drop-outs or inaccuracies using other PCR methods.

Known Drugs Identified by Structure-Based Virtual Screening Are Able to Bind Sigma-1 Receptor and Increase Growth of Huntington Disease Patient-Derived Cells.

Huntington disease (HD) is a devastating and presently untreatable neurodegenerative disease characterized by progressively disabling motor and mental manifestations. The sigma-1 receptor (σ1R) is a protein expressed in the central nervous system, whose 3D structure has been recently determined by X-ray crystallography and whose agonists have been shown to have neuroprotective activity in neurodegenerative diseases. To identify therapeutic agents against HD, we have implemented a drug repositioning strategy consisting of: (i) Prediction of the ability of the FDA-approved drugs publicly available through the ZINC database to interact with σ1R by virtual screening, followed by computational docking and visual examination of the 20 highest scoring drugs; and (ii) Assessment of the ability of the six drugs selected by computational analyses to directly bind purified σ1R in vitro by Surface Plasmon Resonance and improve the growth of fibroblasts obtained from HD patients, which is significantly impaired with respect to control cells. All six of the selected drugs proved able to directly bind purified σ1R in vitro and improve the growth of HD cells from both or one HD patient. These results support the validity of the drug repositioning procedure implemented herein for the identification of new therapeutic tools against HD.

Frequency of the loss of CAA interruption in the HTT CAG tract and implications for Huntington disease in the reduced penetrance range.

PURPOSE: In some Huntington disease (HD) patients, the "loss of interruption" (LOI) variant eliminates an interrupting codon in the HTT CAG-repeat tract, which causes earlier age of onset (AOO). The magnitude of this effect is uncertain, since previous studies included few LOI carriers, and the variant also causes CAG size misestimation. We developed a rapid LOI detection screen, enabling unbiased frequency estimation among manifest HD patients. Additionally, we combined published data with clinical data from newly identified patients to accurately characterize the LOI's effect on AOO. METHODS: We developed a LOI detection polymerase chain reaction (PCR) assay, and screened patients to estimate the frequency of the LOI variant and its effect on AOO. RESULTS: Mean onset for LOI carriers (n = 49) is 20.4 years earlier than expected based on diagnosed CAG size. After correcting for CAG size underestimation, the variant is still associated with onset 9.5 years earlier. The LOI is present in 1.02% of symptomatic HD patients, and in 32.2% of symptomatic reduced penetrance (RP) range patients (36-39 CAGs). CONCLUSION: The LOI causes significantly earlier onset, greater than expected by CAG length, particularly in persons with 36-39 CAG repeats. Detection of this variant has implications for HD families, especially for those in the RP range.

Tracing the mutated HTT and haplotype of the African ancestor who spread Huntington disease into the Middle East.

PURPOSE: We aimed to determine the origin and genetic characteristics of Huntington disease (HD) in the Middle East. METHODS: We performed genetic and genealogical analyses to establish the ancestral origin of the HTT pathgenic variant from a large kindred from Oman (hereafter called the OM-HD-01 pedigree) by single-nucleotide polymorphism and dense haplotype analysis genotyping. RESULTS: We traced the oldest ancestry of the largest, eight-generation, OM-HD-01 pedigree (n = 302 subjects, with 54 showing manifest HD) back to sub-Saharan Africa and identified a unique HD haplotype carried by all pedigree members, which consisted of portions of the C6 and C9 haplotypes and was carried by all affected members. Such a unique HD haplotype was of African origin and appeared to be associated with large CAG repeat expansions on average and high frequency of juvenile-onset HD. Three other families from the same area were also identified and found carrying a Caucasian HD haplotype A, also shared by most families of Arab ancestry. CONCLUSION: Mutated HTT spread into Middle East with a unique haplotype of African origin, appeared to be associated with juvenile-onset, a HD condition frequently occurring in Black Africans, and may have a significant impact on further development of novel targeted genetic therapies.

DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease.

Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1-6 ANN NEUROL 2019;85:296-301.

Phosphorylation of huntingtin at residue T3 is decreased in Huntington's disease and modulates mutant huntingtin protein conformation.

Posttranslational modifications can have profound effects on the biological and biophysical properties of proteins associated with misfolding and aggregation. However, their detection and quantification in clinical samples and an understanding of the mechanisms underlying the pathological properties of misfolding- and aggregation-prone proteins remain a challenge for diagnostics and therapeutics development. We have applied an ultrasensitive immunoassay platform to develop and validate a quantitative assay for detecting a posttranslational modification (phosphorylation at residue T3) of a protein associated with polyglutamine repeat expansion, namely Huntingtin, and characterized its presence in a variety of preclinical and clinical samples. We find that T3 phosphorylation is greatly reduced in samples from Huntington's disease models and in Huntington's disease patients, and we provide evidence that bona-fide T3 phosphorylation alters Huntingtin exon 1 protein conformation and aggregation properties. These findings have significant implications for both mechanisms of disease pathogenesis and the development of therapeutics and diagnostics for Huntington's disease.

Mitochondrial Respiration Changes in R6/2 Huntington's Disease Model Mice during Aging in a Brain Region Specific Manner.

Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington's Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we investigate whether oxidative phosphorylation (OXPHOS) differs across brain regions in juvenile as compared to adult mice and whether such developmental changes might be compromised in the R6/2 mouse model of HD. We study OXPHOS in the striatum, hippocampus, and motor cortex by high resolution respirometry in female wild-type and R6/2 mice of ages corresponding to pre-symptomatic and symptomatic R6/2 mice. We observe a developmental shift in OXPHOS-control parameters that was similar in R6/2 mice, except for cortical succinate-driven respiration. While the LEAK state relative to maximal respiratory capacity was reduced in adult mice in all analyzed brain regions, succinate-driven respiration was reduced only in the striatum and cortex, and NADH-driven respiration was higher as compared to juvenile mice only in the striatum. We demonstrate age-related changes in respirational capacities of different brain regions with subtle deviations in R6/2 mice. Uncovering in situ oxygen conditions and potential substrate limitations during aging and HD disease progression are interesting avenues for future research to understand brain-regional vulnerability in HD.

Effects of stimulus-related variables on mental states recognition in Huntington's disease.

BACKGROUND: Cognitive abnormalities in Huntington's Disease (HD) can involve the specific impairment of the social perspective taking as well as difficulties in recognizing others' mental state many years before the onset of motor symptoms. AIMS: At the scope of assessing how the difficulties in mental state recognition might be an HD early sign before motor symptoms appear, our study was aimed to investigate how the recognition of others' mental states in HD subjects is moderated by different stimulus related features (gender, difficulty (low, medium, high), and valence (positive, negative, neutral) of the mental states that are to be recognized). METHODS: Subjects with premanifest (n = 20) and manifest (n = 40) HD performed the revised 'Reading the Mind in the Eyes Test' and were compared with age-matched healthy controls (HC, 40 subjects per cohort). RESULTS: Our results highlight an early impairment in mental state recognition preceding manifest HD symptoms and a deterioration of these abilities with HD progression. Moreover, we found in HD premanifest subjects an impairment concerning the recognition of negative and neutral mental states, as well as of mental states with moderate recognition difficulty. Finally, we found that participant gender did not influence the performance in recognizing others' mental states, while all participants recognized mental states displayed by females more accurately than those displayed by males. CONCLUSIONS: We conclude that difficulties in the recognition of complex mental states can be considered as an early sign of HD, before evident behavioral manifestations, and peculiar features of the stimulus influence it.

Executive functioning in relapsing-remitting multiple sclerosis patients without cognitive impairment: A task-switching protocol.

BACKGROUND: Cognitive dysfunction affects 40%-65% of multiple sclerosis (MS) patients, most often affecting information processing speed and working memory, mediated by the pre-frontal cortex (PFC). OBJECTIVE: Our study aimed to investigate PFC functioning through a task-switching protocol in relapsing-remitting multiple sclerosis (RRMS) patients without cognitive impairment. METHODS: A total of 24 RRMS patients and 25 controls were enrolled. Two different tasks were performed in rapid and random succession, so that the task was either changed from one trial to the next one (switch trials) or repeated (repetition trials). Switch trials are usually slower than repetitions, causing a so-called switch cost (SC). RESULTS: Patients had worse performance than controls only in the switch trials, as indicated by increased SC and reaction times. Moreover, patients showed a reduced ability to reconfigure the task-set for the execution of a new task and to disengage from the previous one. CONCLUSION: Our results showed a primary deficit in executive control processes involved in the task-switching performance in RRMS patients without cognitive impairment. This deficit may depend on the functional impairment of the PFC, which is essential to adjust behaviour rapidly and flexibly in response to environmental changes, representing one of the most sophisticated human abilities.

Optical coherence tomography (OCT) study in Argentinean Huntington's disease patients.

BACKGROUND: Huntington's disease (HD) is a genetic, rare and progressive neurodegenerative disorder that causes motor and cognitive impairment in midlife patients. Although retinal damage was observed in animal HD models and in patients with other neurodegenerative diseases, we still need confirmation of impairment in HD patients. Optical coherence tomography (OCT) is a non-invasive methodology that analyses the retinal nerve fibre layers (RNFL) and could reflect processes of neurodegeneration. METHODS: A cross-sectional study with 14 HD patients who underwent a spectral domain OCT. Results were compared with a control group. Demographic data were also obtained. RESULTS: Temporal and superior RNFL sectors in HD showed a significant RNFL thinning compared with a control group. However, no differences were identified in mean total RNFL thickness between HD patients and controls. CONCLUSIONS: OCT is a rapid and non-invasive technique that can be investigated in larger cohorts of patients to assess its potential role as a biomarker in HD patients.