Decision Making and the Brain: Neurologists' View

The article reflects the fact, that concepts like decision making and free will have entered the field of cognitive neuroscience towards the end of 20th century. It gives an overview of brain structures involved in decision making and the concept of free will; and presenting the results of clinical observations and new methods (functional neuroimaging, electrophysiology) it postulates possible mechanisms of these processes. We give a review of the neuroanatomy, specially discussing those parts of the brain important to the present topic, because the process of decision making is dependent on deep subcortical as well as superficial cortical structures. Dopamine has a central role in the in process of reward related behaviour and hedonism. A list of brain structures, related to dopamine action, is also given. The article especially concentrates on the Single Photon Emission Computer Tomography studies in patients with Parkinson's disease (neuroimaging), as well as to the studies concerning the Readiness Potential and Endogeneous Potential P300 (electrophysiology). In the end, we discuss the volition, whose functional anatomy overlaps with the functional anatomy of free will and decision making processes.cognitive neuroscience, brain, decision making, free will, electrophysiology, functional imaging, dopamine

The 2022 symposium on dementia and brain aging in low‐ and middle‐income countries: Highlights on research, diagnosis, care, and impact

Two of every three persons living with dementia reside in low‐ and middle‐income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high‐income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC‐focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. Highlights: Two‐thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs

Biomarker Testing: Piercing the Fog of Alzheimer's and Related Dementia

Alzheimer's disease (AD) and related dementia is one of the growing threats to the sustainability of health and care systems in developed countries, and efforts to find therapies have had scant success. The main reasons for this are lack of efficient therapy, which is linked to too late discovery of the disease itself. With this in mind, biomarkers are recognised as an element which can bring a major contribution to research, helping elucidate the disease and the search for treatments. They are also playing an increasing role in early detection and timely diagnosis, which are considered the principal hopes of effective management in the absence of an effective drug. The current arsenal of biomarkers could already, if more widely deployed, provide an effective minimum service to patients and health systems. A concerted action by policy makers and stakeholders could drive progress in access to AD biomarker testing to provide an optimum service in the medium term. This paper discusses how to improve the use of and access to biomarker testing in the detection and diagnosis of AD and other diseases featuring dementia, and how EU healthcare systems could benefit. It outlines the challenges, lists the achievements to date, and highlights the actions needed to allow biomarker testing to deliver more fully on their potential in AD

Biomarker Testing: Piercing the Fog of Alzheimer’s and Related Dementia.

Alzheimer's disease (AD) and related dementia is one of the growing threats to the sustainability of health and care systems in developed countries, and efforts to find therapies have had scant success. The main reasons for this are lack of efficient therapy, which is linked to too late discovery of the disease itself. With this in mind, biomarkers are recognised as an element which can bring a major contribution to research, helping elucidate the disease and the search for treatments. They are also playing an increasing role in early detection and timely diagnosis, which are considered the principal hopes of effective management in the absence of an effective drug. The current arsenal of biomarkers could already, if more widely deployed, provide an effective minimum service to patients and health systems. A concerted action by policy makers and stakeholders could drive progress in access to AD biomarker testing to provide an optimum service in the medium term. This paper discusses how to improve the use of and access to biomarker testing in the detection and diagnosis of AD and other diseases featuring dementia, and how EU healthcare systems could benefit. It outlines the challenges, lists the achievements to date, and highlights the actions needed to allow biomarker testing to deliver more fully on their potential in AD

Sex differences in Parkinson's disease: A transcranial magnetic stimulation study

Background Demographic and clinical studies imply that female sex may be protective for PD, but pathophysiological evidence to support these observations is missing. In early PD, functional changes may be detected in primary motor cortex using transcranial magnetic stimulation. Objective We hypothesised that if pathophysiology differs between sexes in PD, this will be reflected in differences of motor cortex measurements. Methods Forty‐one newly diagnosed PD patients (22 males, 19 females) were clinically assessed using MDS‐UPDRS part III, and various measures of cortical excitability and sensorimotor cortex plasticity were measured over both hemispheres, corresponding to the less and more affected side, using transcranial magnetic stimulation. Twenty‐three healthy (10 men, 13 women) participants were studied for comparison. Results Among patients, no significant differences between sexes were found in age, age of diagnosis, symptom duration, and total or lateralized motor score. However, male patients had disturbed interhemispheric balance of motor thresholds, caused by decreased resting and active motor thresholds in the more affected hemisphere. Short interval intracortical inhibition was more effective in female compared to male patients in both hemispheres. Female patients had a preserved physiological focal response to sensorimotor plasticity protocol, whereas male patients showed an abnormal spread of the protocol effect. Conclusion The study provides one of the first neurophysiological evidences of sex differences in early PD. Female patients have a more favorable profile of transcranial magnetic stimulation measures, possibly reflecting a more successful cortical compensation or delayed maladaptive changes in the sensorimotor cortex. © 2019 International Parkinson and Movement Disorder Societ

Characterizing advanced Parkinson’s disease: OBSERVE-PD observational study results of 2615 patients

Abstract Background There are currently no standard diagnostic criteria for characterizing advanced Parkinson’s disease (APD) in clinical practice, a critical component in determining ongoing clinical care and therapeutic strategies, including transitioning to device-aided treatment. The goal of this analysis was to determine the proportion of APD vs. non-advanced PD (non-APD) patients attending specialist PD clinics and to demonstrate the clinical burden of APD. Methods OBSERVE-PD, a cross-sectional, international, observational study, was conducted with 2615 PD patients at 128 movement disorder centers in 18 countries. Motor and non-motor symptoms, activities of daily living, and quality-of-life end points were assessed. The correlation between physician’s global assessment of advanced PD and the advanced PD criteria from a consensus of an international group of experts (Delphi criteria for APD) were evaluated. Results According to physician’s judgment, 51% of patients were considered to have APD. There was a moderate correlation between physician’s judgment and Delphi criteria for APD (K = 0.430; 95% CI 0.406–0.473). Activities of daily living, motor symptom severity, dyskinesia duration/disability, “Off” time duration, non-motor symptoms, and quality-of-life scores were worse among APD vs. non-APD patients (p < 0.0001 for all). APD patients (assessed by physicians) had higher disease burden by motor and non-motor symptoms compared with non-APD patients and a negative impact on activities of daily living and quality of life. Conclusions These findings aid in identifying standard APD classification parameters for use in practicing physicians. Improvements in identification of APD patients may be particularly relevant for optimizing treatment strategies including transitioning to device-aided treatment

The syndrome of deafness-dystonia: Clinical and genetic heterogeneity

The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions. (c) 2013 Movement Disorder Societ

Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers

Introduction: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia. Methods: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers. Results: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up. Discussion: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support