Family Functioning, Maternal Depression, and Adolescent Cognitive Flexibility and Its Associations with Adolescent Depression: A Cross-Sectional Study.

BACKGROUND: This study explores family functioning and its associations with adolescent major depressive disorder (MDD), comparing its dynamics with healthy counterparts. Family functioning (cohesion, flexibility, communication, and satisfaction), maternal depressive symptoms, postpartum depression history, parental divorce, parental alcohol abuse, and the adolescents' cognitive flexibility, are examined. The research incorporates the perspectives of both adolescents and mothers. METHODS: The sample includes 63 mother-teenager dyads in the clinical group and 43 in the control group. Instruments encompass the Family Adaptability and Cohesion Evaluation Scales (FACES IV), Children's Depression Inventory (CDI-2), Beck Depression Inventory (BDI-II), The Brixton Spatial Anticipation Test, and structured interviews. RESULTS: Families of adolescents with MDD exhibit lower flexibility, cohesion, communication, and overall satisfaction. Depressed adolescents display reduced cognitive flexibility. Discrepancies were observed between adolescents' and mothers' perspectives as associated with adolescents' MDD. Teenagers emphasized the severity of maternal depressive symptoms, while mothers highlighted the importance of family cohesion and flexibility. CONCLUSIONS: This study emphasizes a holistic strategy in addressing adolescent depression, including family-based assessment and therapy. Screening for maternal depressive symptoms is identified as valuable. Cognitive flexibility also needs to be addressed during therapy for depression in adolescence.

The misidentification syndromes and source memory deficits with their neuroanatomical correlates from neuropsychological perspective.

The suggested model is discussed with reference to two clinical populations with memory disorders - patients with misidentification syndromes and those with source memory impairment, both of whom may present with (broadly conceived) déjà vu phenomenon, without insight into false feeling of familiarity. The role of the anterior thalamic nucleus and retrosplenial cortex for autobiographical memory and familiarity is highlighted.

Is there sufficient evidence for the association between executive dysfunction and academic performance in adolescents with major depressive disorder?: a systematic review.

Adult depression, undoubtedly associated with executive dysfunction, leads to poor work performance. As depression in adolescents may have a negative impact on school performance, we aimed to analyse the possible relationship between selected executive deficits and academic performance. Executive dysfunctions may have more severe consequences on school performance at high school, as this stage of education requires engagement in long-term goals, whether writing an essay or preparing for an exam. Whilst inhibitory control is necessary at all educational stages, it seems that planning and decision-making play a greater role in high school than in primary school. We reviewed studies on executive functions conducted in adolescents diagnosed with major depressive disorder (MDD) to establish the possible relationship between executive processes and school performance in depressed adolescents. The search identified 5 studies addressing planning and decision-making in adolescents with MDD, but none of those studies reported educational achievement. We identified a considerable gap in the research on the functional impact of depression in adolescents. Identifying the link between specific executive deficits and school performance could guide tailored therapeutic interventions.

Perry Disease: Expanding the Genetic Basis.

Background: Perry disease (or Perry syndrome [PS]) is a hereditary neurodegenerative disorder inevitably leading to death within few years from onset. All previous cases with pathological confirmation were caused by mutations within the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of the DCTN1 gene. Objectives: This paper presents the first clinicopathological report of PS due to a novel DCTN1 mutation outside the CAP-Gly domain. Methods: Clinical and pathological features of the new variant carrier are compared with another recently deceased PS case with a well-known pathogenic DCTN1 mutation and other reported cases. Results and Conclusions: We report a novel DCTN1 mutation outside the CAP-Gly domain that we demonstrated to be pathogenic based on clinical and autopsy findings.

Measuring cognitive impairment and monitoring cognitive decline in Huntington's disease: a comparison of assessment instruments.

BACKGROUND: Progressive cognitive decline is an inevitable feature of Huntington's disease (HD) but specific criteria and instruments are still insufficiently developed to reliably classify patients into categories of cognitive severity and to monitor the progression of cognitive impairment. METHODS: We collected data from a cohort of 180 positive gene-carriers: 33 with premanifest HD and 147 with manifest HD. Using a specifically developed gold-standard for cognitive status we classified participants into those with normal cognition, those with mild cognitive impairment, and those with dementia. We administered the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), the MMSE and the UHDRS cogscore at baseline, and at 6-month and 12-month follow-up visits. Cutoff scores discriminating between the three cognitive categories were calculated for each instrument. For each cognitive group and instrument we addressed cognitive progression, sensitivity to change, and the minimally clinical important difference corresponding to conversion from one category to another. RESULTS: The PD-CRS cutoff scores for MCI and dementia showed excellent sensitivity and specificity ratios that were not achieved with the other instruments. Throughout follow-up, in all cognitive groups, PD-CRS captured the rate of conversion from one cognitive category to another and also the different patterns in terms of cognitive trajectories. CONCLUSION: The PD-CRS is a valid and reliable instrument to capture MCI and dementia syndromes in HD. It captures the different trajectories of cognitive progression as a function of cognitive status and shows sensitivity to change in MCI and dementia.

A Patient with Corticobasal Syndrome and Progressive Non-Fluent Aphasia (CBS-PNFA), with Variants in ATP7B, SETX, SORL1, and FOXP1 Genes.

Our aim was to analyze the phenotypic-genetic correlations in a patient diagnosed with early onset corticobasal syndrome with progressive non-fluent aphasia (CBS-PNFA), characterized by predominant apraxia of speech, accompanied by prominent right-sided upper-limb limb-kinetic apraxia, alien limb phenomenon, synkinesis, myoclonus, mild cortical sensory loss, and right-sided hemispatial neglect. Whole-exome sequencing (WES) identified rare single heterozygous variants in ATP7B (c.3207C>A), SORL1 (c.352G>A), SETX (c.2385_2387delAAA), and FOXP1 (c.1762G>A) genes. The functional analysis revealed that the deletion in the SETX gene changed the splicing pattern, which was accompanied by lower SETX mRNA levels in the patient's fibroblasts, suggesting loss-of-function as the underlying mechanism. In addition, the patient's fibroblasts demonstrated altered mitochondrial architecture with decreased connectivity, compared to the control individuals. This is the first association of the CBS-PNFA phenotype with the most common ATP7B pathogenic variant p.H1069Q, previously linked to Wilson's disease, and early onset Parkinson's disease. This study expands the complex clinical spectrum related to variants in well-known disease genes, such as ATP7B, SORL1, SETX, and FOXP1, corroborating the hypothesis of oligogenic inheritance. To date, the FOXP1 gene has been linked exclusively to neurodevelopmental speech disorders, while our study highlights its possible relevance for adult-onset progressive apraxia of speech, which guarantees further study.

Does progressive aphantasia exist? The hypothetical role of aphantasia in the diagnosis of neurodegenerative diseases.

Aphantasia is a heterogeneous neuropsychological syndrome consisting of the inability to create mental images. We argue that its progressive form may be a harbinger of dementia. Aphantasia may manifest as the inability to create any mental images or to create complex scenes, inability to spontaneously initiate generation of mental images, and/or inability to visualize a sequence of events.

Is deep brain stimulation effective in Huntington's Disease? - a systematic literature review.

INTRODUCTION: Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder. Substantial for a diagnosis of the disease are motor disorders, with chorea as a hallmark symptom. Other disease manifestations include cognitive dysfunction and psychiatric disorders. Currently, pharmacological treatment plays the most important role in the therapy of HD patients. However, deep brain stimulation (DBS) is considered a potential therapeutic option. AIM OF THE STUDY: Systematic review of current literature on DBS efficacy and safety in the management of motor, behavioural and cognitive functions in patients with HD. MATERIAL AND METHODS: A systematic review was conducted with the use of the Scopus database and the following search criteria: TITLE (huntington*) AND TITLE-ABS-KEY ('deep brain stimulation' OR 'neuromodulation'). Our search criteria included original studies with at least five patients, reporting any motor, cognitive and/or behavioural, and functional assessment data with at least a 6-month follow-up. Finally, four selected publications were analysed. RESULTS: In all analysed publications, we found a statistically significant improvement of Unified Huntington's Disease Rating Scale (UHDRS) chorea subscore by an average of 40, to over 60% after DBS implantation. Heterogeneous results were obtained for UHDRS total motor score. DBS did not improve functional capacity of HD patients in the analysed studies. We found no systematic assessment concerning the effect of DBS in HD on behaviour, cognition or speech. CONCLUSIONS: DBS implantation could be considered as a therapeutic option for patients with severe, drug-resistant chorea. However, the evidence for this is limited. To date, no high-quality data based on randomised controlled trials supports the long-term safety and efficacy of DBS in HD. This treatment option should therefore currently be considered as investigational.

Computer Aided Written Character Feature Extraction in Progressive Supranuclear Palsy and Parkinson's Disease.

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) are neurodegenerative movement disorders associated with cognitive dysfunction. The Luria's Alternating Series Test (LAST) is a clinical tool sensitive to both graphomotor problems and perseverative tendencies that may suggest the dysfunction of prefrontal and/or frontostriatal areas and may be used in PD and PSP assessment. It requires the participant to draw a series of alternating triangles and rectangles. In the study, two clinical groups-51 patients with PD and 22 patients with PSP-were compared to 32 neurologically intact seniors. Participants underwent neuropsychological assessment. The LAST was administered in a paper and pencil version, then scanned and preprocessed. The series was automatically divided into characters, and the shapes were recognized as rectangles or triangles. In the feature extraction step, each rectangle and triangle was regarded both as an image and a two-dimensional signal, separately and as a part of the series. Standard and novel features were extracted and normalized using characters written by the examiner. Out of 71 proposed features, 51 differentiated the groups (p < 0.05). A classifier showed an accuracy of 70.5% for distinguishing three groups.

The Impact of Subthalamic Deep Brain Stimulation on Restless Legs Syndrome in Parkinson's Disease.

INTRODUCTION: The study aimed at evaluating the effect of subthalamic deep brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) patients. MATERIALS AND METHODS: We assessed the presence of RLS before and 6 and 12 months after surgery in 36 patients. Differences between patients with RLS, without RLS, and with remission of RLS in terms of sleep measures (interview and validated questionnaires) and nonmotor symptoms (NMS). Polysomnography (PSG) was performed in 24 patients. Simple and multiple regression models were used to identify potential predictors of RLS outcome after DBS-STN. RESULTS: Before DBS-STN 14 of the 36 patients (39%) were diagnosed with RLS. DBS-STN resulted in the resolution of RLS in 43% (n = 6) and the emergence of RLS in 2 (9%) patients. During the study, 20 patients remained without RLS and the patients with unremitting RLS (n = 8) experienced alleviation of symptoms. At baseline patients with RLS had higher Non-Motor Symptoms Scale (NMSS) total and sleep domain, Unified Parkinson's Disease Rating Scale (UPDRS) part IV and lower Parkinson's Disease Sleep Scale (PDSS) scores. There were no differences between the groups without and with RLS in terms of PSG recordings. CONCLUSION: DBS-STN provided relief of symptoms in most of the patients with PD and RLS. We found that RLS was associated with worse subjective sleep quality, more severe NMS, and complications of levodopa therapy. DBS-STN may have direct impact on RLS rather than related indirectly through post-surgery change in medications.

Two Rare Variants in PLAU and BACE1 Genes-Do They Contribute to Semantic Dementia Clinical Phenotype?

We have performed whole-genome sequencing to identify the genetic variants potentially contributing to the early-onset semantic dementia phenotype in a patient with family history of dementia and episodic memory deficit accompanied with profound semantic loss. Only very rare variants of unknown significance (VUS) have been identified: a nonsense variant c.366C>A/p.Cys122* in plasminogen activator, urokinase (PLAU) and a missense variant c.944C>T/p.Thr315Met in ß-site APP-cleaving enzyme 1 (BACE1)-along with known disease-modifying variants of moderate penetrance. Patient-derived fibroblasts showed reduced PLAU and elevated BACE1 mRNA and protein levels compared to control fibroblasts. Successful rescue of PLAU mRNA levels by nonsense-mediated mRNA decay (NMD) inhibitor (puromycin) confirmed NMD as the underlying mechanism. This is the first report of the PLAU variant with the confirmed haploinsufficiency, associated with semantic dementia phenotype. Our results suggest that rare variants in the PLAU and BACE1 genes should be considered in future studies on early-onset dementias.

Arithmetic Word-Problem Solving as Cognitive Marker of Progression in Pre-Manifest and Manifest Huntington's Disease.

BACKGROUND: Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington's disease (HD). OBJECTIVE: Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations between arithmetic task performance and other neuropsychological tasks. METHODS: We collected data from a multicenter cohort of 165 HD gene-mutation carriers. The sample consisted of 31 premanifest participants: 16 far-from (>12 years estimated time to diagnosis; preHD-A) and 15 close-to (≤12 years estimated time to diagnosis; preHD-B), 134 symptomatic patients (early-mild HD), and 37 healthy controls (HC). We compared performance between groups and explored the associations between arithmetic word-problem solving and neuropsychological and clinical variables. RESULTS: Total arithmetic word-problem solving scores were lower in preHD-B patients than in preHD-A (p < 0.05) patients and HC (p < 0.01). Early-mild HD patients had lower scores than preHD patients (p < 0.001) and HC (p < 0.001). Compared to HC, preHD and early-mild HD participants made more errors as trial complexity increased. Moreover, arithmetic word-problem solving scores were significantly associated with measures of global cognition (p < 0.001), frontal-executive functions (p < 0.001), attention (p < 0.001) visual working memory (p < 0.001), mental rotation (p < 0.001), and confrontation naming (p < 0.05). CONCLUSION: Arithmetic word-problem solving is affected early in the course of HD and is related to deficient processes in frontal-executive and mentalizing-related processes.

Clinical, pathological and genetic characteristics of Perry disease-new cases and literature review.

BACKGROUND AND PURPOSE: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease. METHODS: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed. RESULTS: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play. CONCLUSIONS: Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.

The assessment of cognitive and behavioural disturbances in vascular cognitive impairment (VCI) - recommendations of an expert working group.

With newer research-based classification systems, the term Vascular Cognitive Impairment (VCI) is now preferred to vascular dementia. VCI is an umbrella term that includes all forms of cognitive deficits ranging from mild cognitive impairment of vascular origin (VaMCI) to vascular dementia (VaD). The new VCI construct takes into account the fact that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease such as chronic hypoperfusion that might account for the pattern of cognitive deficits associated with vascular dementia. The key to defining the spectrum of VCI is neuropsychological testing, bedside or office-based clinical examination, and neuroimaging. The lack of specific cognitive tools that are sufficiently sensitive to detect subtle deficits makes the assessment of cognitive impairment difficult. Prospective cross-sectional and longitudinal studies of VCI from different settings are therefore required. Although there have been few published reports, behavioural and psychological symptoms (BPS) are inherently present in VCI from the onset and during the course of the disease. Besides the type of population (i.e. clinical, community or nursing-home settings), the definition of VCI/VaD and the instruments used, and differences in the prevalence and pattern of BPS between various studies, could be due to other, often unconsidered, factors such as gender, age, education, use of medication and VCI/VaD severity.

Cognitive and behavioral profile of Perry syndrome in two families.

OBJECTIVE: Perry syndrome (PS) is a rare neurodegenerative disorder with autosomal dominant inheritance caused by point mutations in DCTN1 and characterized by parkinsonism, hypoventilation, weight loss, and psychiatric symptoms. Even though behavioral manifestation is a main feature of PS, detailed neuropsychological assessment was not performed in this cohort. In this study, the neuropsychological profile of individuals from one Polish and one Colombian family are presented. METHODS: Detailed clinical and neuropsychological data were obtained from Polish and Colombian families. Clinical and neuropsychological examinations on the proband from the Polish family were performed 6 times over 11 years. Each of 3 individuals from the Colombian family received a clinical and neuropsychological assessment. RESULTS: The neurologic examination showed severe parkinsonism, levodopa-induced motor fluctuations, and dyskinesias in all cases. Respiratory insufficiency was observed in 2 patients and weight loss in 1 individual. Neuropsychological assessment revealed predominant deterioration of working memory and learning capacity in the Polish patient. He also demonstrated compulsive behaviors, such as excessive shopping and eating, but only in the "on" phase. In the Colombian family, attentional deficits were present in 2 out of 3 cases. Out of 4 reported cases apathy and depressed mood were present in 2 individuals. Two cases demonstrated impulsivity and one had episodes of hypomania. CONCLUSIONS: Both of these families revealed relatively similar neurologic and neuropsychological profiles. The Polish patient's behavioral and neuropsychological profile was mostly compatible with a behavioral variant of frontotemporal dementia. Of note, not only depression and apathy, but also impulsivity can occur in PS.

Utility of the Parkinson's disease-Cognitive Rating Scale for the screening of global cognitive status in Huntington's disease.

BACKGROUND: Cognitive impairment is an essential feature of Huntington's disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking. OBJECTIVES: We aimed to explore the utility of the Parkinson's disease-Cognitive Rating Scale (PD-CRS) for the screening of global cognition in HD. METHODS: A multicenter cohort of 132 HD patients at different disease stages and 33 matched healthy controls were classified as having preserved cognition, mild cognitive impairment (HD-MCI) or dementia (HD-Dem) according to the Clinical Dementia Rating and Functional Independence Score. The PD-CRS and the Mini-Mental State Examination were administered. Receiver operating characteristic curve analysis was used to determine optimal cutoffs to differentiate patients according to their cognitive status. RESULTS: A PD-CRS cutoff score ≤ 81/82 was optimal to detect HD-MCI (sensitivity = 93%; specificity = 80%; area under the curve (AUC) = 0.940), and ≤ 63/64 was optimal to detect HD-Dem (sensitivity = 90%; specificity = 87%; AUC = 0.933). MMSE scores failed to show robust psychometric properties in this context. DISCUSSION: The PD-CRS is a valid and reliable instrument to assess global cognition in HD in routine clinical care and clinical trials.

Prevalence and predictors of post-stroke spasticity and its impact on daily living and quality of life.

BACKGROUND AND AIMS: The present study aimed to assess the frequency of spasticity in a single-centre cohort of stroke patients in a one-year follow-up, its predictors, and its impact on the activities of daily living (ADL) and health-related quality of life (HRQoL). MATERIAL AND METHODS: A group of 121 consecutive patients with hemiparesis (aged 73 ± 11 years) was selected for further observation, out of 381 Stroke Department patients during one year. At three follow-up assessments three, six and 12 months after stroke, muscle tone and muscle weakness were rated using Modified Ashworth Scale (MAS) and Medical Research Council (MRC); Activities of Daily Living (ADL) and Health Related Quality of Life (HRQoL) were evaluated using the Barthel Index (BI), Modified Rankin Scale (mRS) and an SF-36 questionnaire. RESULTS: Fifty five of 121 (45%) patients after three months had developed spasticity (MAS ≥ 1), and in 19 of the 121 (15%) this spasticity was severe. After one year, 33/94 (35%) patients showed spasticity, and in 19/94 (20%) it was severe. Baseline muscle weakness (MRC), stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS), and greater disability (BI), were the most significant predictors of persistent post-stroke spasticity. Patients with spasticity had worse HRQoL in terms of their physical functioning, role limitations, physical pain, and vitality. CONCLUSION: Spasticity, which affects a significant proportion of stroke survivors, was present in 35% of our patients at 12 months after stroke. It has a major impact on both ADL and HRQoL. Severe disability and muscle weakness are the most important predictors of persistent post-stroke spasticity.

The impact of subthalamic deep brain stimulation on sleep and other non-motor symptoms in Parkinson's disease.

INTRODUCTION: The non-motor symptoms have a major impact on quality of life in patients with Parkinson Disease (PD). We present results of the study on the impact of subthalamic deep brain stimulation (DBS-STN) on sleep and other non-motor symptoms in PD patients. MATERIALS AND METHODS: Thirty-six patients with advanced PD were included into the study. Twenty four were evaluated with two-night polysomnography (PSG) before surgery and at 6 months after DBS programming. The whole group (n = 36) was assessed using motor, non-motor symptoms (sleep disturbances in particular) and quality of life measures (QoL), before surgery, 6 and 12 months after DBS programming. RESULTS: DBS-STN resulted in the significant deterioration of objective sleep parameters, as assessed by PSG, mostly in terms of total sleep time, sleep efficiency, duration of N1 and N2 sleep, wakefulness after sleep onset and sleep latency. At the same time, improvement in the subjective sleep measures, other non-motor symptoms (particularly fatigue, cardiovascular, gastrointestinal, and sexual symptoms) and QoL was identified. The subjective improvement of sleep, other non-motor symptoms and QoL was most prominent in the first 6 months after DBS-STN, diminished slightly (being still better than before surgery) after 12 months, in parallel to mood deterioration. CONCLUSION: DBS-STN resulted in the subjective sleep quality improvement with worsening of objective (PSG) sleep parameters after 6 months. After 12 months all sleep clinical outcome measures were still better than before surgery, albeit worse when compared to the first follow-up visit. Subjective sleep quality correlated positively with mood.