Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: the CADDementia challenge.

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n=30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

Correction: The psychological impact of the COVID-19 pandemic in Portugal: The role of personality traits and emotion regulation strategies.

[This corrects the article DOI: 10.1371/journal.pone.0269496.].

The psychological impact of the COVID-19 pandemic in Portugal: The role of personality traits and emotion regulation strategies.

Recent evidence suggests that both personality traits (PT) and emotion regulation (ER) strategies play an important role in the way people cope with the COVID-19 pandemic. The aim of this study was two folded. First, to longitudinally investigate the psychological distress (depression, anxiety, and stress levels) taking in consideration PT and ER strategies in 3 different moments: during the first lockdown period (April/20), at the first deconfinement (May/20) and 1-month after the first deconfinement (Jun/20)-Experiment I. Second, to cross-sectionally evaluate the impact of the pandemic in psychological distress and the correlates with PT and ER 6-months after the first deconfinement November/20 to February/21 -Experiment II. A total of 722 volunteers (Experiment I = 180; Experiment II = 542) aged 18 years or older participated in this online survey. The findings from Experiment I show that psychological distress decreased after the lockdown period, however, neuroticism traits predicted higher levels of depression, anxiety and stress symptoms, while difficulties in ER strategies were identified as a risk factor for depression and stress. For experiment II, neuroticism traits and being infected with COVID-19 were associated to higher levels of symptomatology, while unemployment and the use of emotional suppression strategies to cope with emotional situations were associated to depressive and anxiety symptoms. Although the psychological impact of the COVID-19 outbreak decreased over time in our sample, the current findings suggest that difficulties in emotional regulation and high levels of neuroticism traits might be potential risk factors for psychiatric symptomatology during the COVID-19 pandemic. Thus, people with difficulties in ER and neuroticism traits would benefit from psychological interventions that provide personality-appropriate support and promote emotion regulation skills during stressful events, such as the case of the global pandemic.

Feasibility and Impact of a Multicomponent Exercise Intervention in Patients With Alzheimer's Disease: A Pilot Study.

This quasi-experimental, nonrandomized study examined the feasibility and impact of a multicomponent (MT) intervention on 7 community-dwelling individuals diagnosed with probable Alzheimer's disease (AD) at mild to moderate stage. During 6 months, patients with AD and their caregivers were submitted to a biweekly exercise program, including muscle strengthening, aerobics, balance, and postural exercises. The following tests were used: Senior Fitness Test and Incremental Treadmill Test, Disability Assessment for Dementia Scale, Alzheimer Disease Assessment Scale-Cognitive, and Quality of Life-Alzheimer's. Attendance and retention mean rates were high (86% and 78%, respectively). No adverse events occurred. Results revealed a significant beneficial effect on cardiorespiratory fitness ( P = .028), upper ( P = .018) and lower ( P = .026) body muscle strength, agility ( P = .018), and ability to perform daily activities ( P = .018). Data suggest that a biweekly MT intervention is feasible to conduct in patients with AD. Findings also suggest a potential positive effect on mitigating cognitive decline and in positively influencing quality of life.

Difficult case of a rare form of familial Alzheimer's disease with PSEN1 P117L mutation.

Less than 10% of Alzheimer's disease (AD) cases are familial. Presenilin-1 (PSEN1) mutations are the most frequent aetiology and may be associated to atypical neurological manifestations. We report the case of a 27-year-old right-handed man, ensuing with mild cognitive impairment, motor discoordination and axial myoclonus after a parachute accident. At age 32 he was referred to our neurology clinic, presenting cognitive impairment, cerebellar syndrome, axial myoclonus and hypomimia, without other signs of parkinsonism. Because of absence of family history, he was worked up along the line of spinal ataxic disorders. Later, he developed pseudobulbar affect, cognitive deterioration, right upper limb paresis and spastic paraparesis. Subsequent investigation identified a PSEN1 P117L mutation and the diagnosis of autosomal dominant AD was made. This case illustrates the diagnostic challenge imposed by atypical presentation of de novo PSEN1 mutation, leading to unnecessary investigation. Genetic study might be essential for defining the diagnosis.

"Living together with dementia": Training programme for family caregivers - A study protocol.

HIGHLIGHTS: The increased incidence of dementia places the family in the role of caregiver.It is important to create, to implement and to validate training programmes for family caregivers of people with dementia living at home.The programme "Living together with dementia" addressed in this protocol seeks to be a response to empower these caregivers. INTRODUCTION: Due the increase incidence of Dementia, the creation, implementation and evaluation of the effectiveness of training programmes for family caregivers of people with dementia living at home should be a goal of health professionals. The aim of this paper is to describe the randomised control trial protocol that will assess the effectiveness of the training programme for family caregivers who care for people with dementia at home "Living together with Dementia". METHODS: Randomised control trial. Family caregivers of people with dementia in early and moderate stages will be recruited through a neurology appointment at the São João Hospital Centre, Porto-Portugal. The inclusion criteria employed will be as follows: to be the main caregiver of the person with dementia; to be literate; the care target has dementia in early or moderate stage; the person with dementia does not suffer from any other severe mental pathology. Caregivers will be randomised and assigned to control and experimental groups. 3 assessment moments will take place: initial, after the intervention and a follow up of 3 to 6 months. The assessment instruments include a survey containing sociodemographic data, Caregiver Burden Scale, Caregiver Assessment Satisfaction Index and Caregiver Assessment Difficulties Index. The participants of the experimental group will be submitted to a 7-week individual psychoeducational programme. The study was approved by the Health Ethics Committee of the São João Hospital Centre in September 2015. DISCUSSION: This programme might prove an asset to family caregivers of people with dementia living at home, since it pinpoints understanding and preparation of their role. It also facilitates the intervention of health professional, as it features as a guideline for their performance with this target population.

Pediatric Multiple Sclerosis in Portugal: A Multicentre Study.

INTRODUCTION: Multiple sclerosis is most often diagnosed among young adults but less frequently it may present during childhood or adolescence. In Portugal, there has been only one previous single-center, pediatric multiple sclerosis study. The main objective was the evaluation of the demographic, clinical, laboratorial and neuroradiological characteristics of patients with pediatric-onset multiple sclerosis in Portugal. The secondary objectives were to compare the characteristics of childhood-onset multiple sclerosis and adolescent-onset multiple sclerosis and to characterize the treatments prescribed. MATERIAL AND METHODS: We performed a retrospective observational, multicentric study. We reviewed data of all patients with multiple sclerosis younger than 18 years at the onset of their first multiple sclerosis symptoms. RESULTS: There were 46 patients (72% female) included with a mean age at diagnosis of 16.1 years. Six cases had childhood-onset and 40 cases had adolescence-onset. The median value of Expanded Disability Status Scale was two. Relapsing-remitting multiple sclerosis was most prevalent (98% of cases). In the cerebrospinal fluid study, 74% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (98% of cases), whereas the cervical segment was the most frequently affected in the spinal cord. All the patients enrolled in the study underwent immunomodulatory therapy, 75% ofpatients with beta-interferon. Concerning differences between the childhood and the adolescent groups, we found a greater proportion of male patients and of individuals with cerebrospinal fluid pleocytosis among the childhood-onset group. DISCUSSION: This study provides new data on pediatric multiple sclerosis characteristics in Portugal and our results are similar to previously reported data in other parts of the worldConclusion: This is the first multicentric study characterizing pediatric multiple sclerosis in Portugal. The mechanisms underlying the particularities of pediatric multiple sclerosis remain largely unknown and further studies are required.

Introdução: A esclerose múltipla é habitualmente diagnosticada em adultos jovens mas, mais raramente, pode manifestar-se durante a infância ou adolescência. Os dados sobre a esclerose múltipla pediátrica em Portugal são escassos. O objectivo principal deste estudo é a avaliação das características demográficas, clínicas, laboratoriais e neurorradiológicas da esclerose múltipla de início em idade pediátrica em Portugal. Os objetivos secundários consistem na comparação entre a esclerose múltipla de início na infância e a esclerose múltipla de início na adolescência e na caracterização dos tratamentos prescritos. Material e Métodos: Realizou-se um estudo retrospectivo, observacional e multicêntrico, que consistiu na análise dos dados de todos os doentes com apresentação da EM antes dos 18 anos. Resultados: Incluíram-se 46 doentes (72% do sexo feminino), com uma idade média de diagnóstico de 16,1 anos. Seis casos tiveram início na infância, 40 na adolescência. A esclerose múltipla apresentou-se em 98% dos casos com a forma surto-remissão. O estudo do líquor revelou bandas oligoclonais em 74% dos doentes. A ressonância magnética encefálica mostrou predominantemente lesões supratentoriais (98% dos casos), enquanto que a ressonância medular revelou que o segmento cervical foi o mais frequentemente afectado. Todos os doentes iniciaram terapêutica imunomoduladora (75% com interferão ß). Relativamente às diferenças entre os dois grupos etários, encontrámos uma maior proporção de doentes do sexo masculino e com pleocitose no grupo com apresentação na infância. Discussão: Este trabalho fornece novos dados sobre as características da esclerose múltipla pediátrica em Portugal e os resultados são semelhantes aos reportados em outras partes do mundo. Conclusão: Este é o primeiro estudo multicêntrico português sobre a esclerose múltipla com apresentação na infância e adolescência. Mais estudos são necessários para clarificar os mecanismos subjacentes às particularidades da esclerose múltipla pediátrica.

Determination of bopindolol using the flow injection technique coupled with solid phase extraction.

In the proposed procedure, the determination of bopindolol using a flow injection analysis (FIA) technique, with spectrophotometric detection at 635 nm, is described. The method is based on the production of a green, water-soluble complex with ferric ions in acid medium. The automated lab-made FIA system was used for the direct determination of bopindolol in tablets. Bopindolol was adsorbed onto the solid phase in a mini-column, which was integrated directly into the flow system. The positive feature of the use of solid phase extraction (SPE) was the pre-concentration of bopindolol (seven times). The sample throughput was 50 samples per hour. Using the SPE method, bopindolol was determined with a linear range from 125 to 1000 microg ml(-1) (Relative standard deviation (R.S.D.)=1.87%), with a detection limit (3sigma) of 70 microg ml(-1). The method was applied to the determination of bopindolol in Sandonorm tablets. The results obtained were compared with a conventional HPLC method, both analytical techniques were in good agreement.

Isolated III cranial nerve palsy: a Hodgkin's lymphoma?

A 69-year-old woman developed ptosis and diplopia due to an isolated pupil-involving left oculomotor nerve palsy. General examination was unremarkable. Initial workup showed a mild increase in cerebrospinal fluid proteins. Imaging studies were remarkable for a left oculomotor nerve enhancement in brain MRI and hyperfixation along the nerve's pathway in full body single-photon emission CT. Assuming the possible diagnosis of neurosarcoidosis, the patient was started on high-dose methylprednisolone. Three months later she developed pancytopenia. A bone marrow biopsy was performed and histopathology revealed infiltration by Hodgkin's lymphoma. Adriamycin, bleomycin, vinblastine, dacarbazine protocol chemotherapy was started and full haematological remission obtained after four cycles, despite mild oculomotor nerve palsy persisted. Isolated oculomotor palsy as the first presenting manifestation of a lymphoma is rare and alternative differential diagnosis must be considered in the absence of other lymphoma manifestations. In this case as with many rare initial manifestations of common diseases watchful waiting was crucial to the correct diagnosis and treatment strategy.

Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL): a pediatric case report.

The syndrome of transient headache and neurologic deficits associated with cerebrospinal fluid lymphocytosis (HaNDL) is characterized by 1 or more episodes of severe headache, transient neurologic deficits, and lymphocytic pleocytosis in the cerebrospinal fluid. It is a benign and self limited disorder seldom reported in pediatric age. We report the case of a 14-year-old girl who suffered from 2 episodes of headache with transient focal neurologic deficits and pleocytosis consistent with the syndrome of HaNDL. This entity should be taken into account as a differential diagnosis in otherwise healthy children presenting with recurrent headache and acute neurologic deficits. Repeated use of invasive and expensive laboratory and imaging investigations can be avoided when the diagnosis of the syndrome of HaNDL is correctly established.

Cognitive impairment and dementia in Parkinson's disease: clinical features, diagnosis, and management.

Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. In addition to classical motor symptoms, non-motor features are now widely accepted as part of the clinical picture, and cognitive decline is a very important aspect of the disease, as it brings an additional significant burden for the patient and caregivers. The diagnosis of cognitive decline in PD, namely mild cognitive impairment (MCI) and dementia, can be extremely challenging, remaining largely based on clinical and cognitive assessments. Diagnostic criteria and methods for PD dementia and MCI have been recently issued by expert work groups. This manuscript has synthesized relevant data in order to obtain a pragmatic and updated review regarding cognitive decline in PD, from milder stages to dementia. This text will summarize clinical features, diagnostic methodology, and therapeutic issues of clinical decline in PD. Relevant clinical genetic issues, including recent advances, will also be approached.