Non-invasive brain stimulation for gambling disorder: a systematic review

Background:Gambling disorder (GD) is the most common behavioral addiction and shares pathophysiological and clinical features with substance use disorders (SUDs). Effective therapeutic interventions for GD are lacking. Non-invasive brain stimulation (NIBS) may represent a promising treatment option for GD. Objective:This systematic review aimed to provide a comprehensive and structured overview of studies applying NIBS techniques to GD and problem gambling. Methods:A literature search using Pubmed, Web of Science, and Science Direct was conducted from databases inception to December 19, 2019, for studies assessing the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (t-DCS) on subjects with GD or problem gambling. Studies using NIBS techniques on healthy subjects and those without therapeutic goals but only aiming to assess basic neurophysiology measures were excluded. Results:A total of 269 articles were title and abstract screened, 13 full texts were assessed, and 11 were included, of which six were controlled and five were uncontrolled. Most studies showed a reduction of gambling behavior, craving for gambling, and gambling-related symptoms. NIBS effects on psychiatric symptoms were less consistent. A decrease of the behavioral activation related to gambling was also reported. Some studies reported modulation of behavioral measures (i.e., impulsivity, cognitive and attentional control, decision making, cognitive flexibility). Studies were not consistent in terms of NIBS protocol, site of stimulation, clinical and surrogate outcome measures, and duration of treatment and follow-up. Sample size was small in most studies. Conclusions:The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the efficacy of NIBS interventions for GD. Further methodologically sound, robust, and well-powered studies are needed

Non-invasive brain and spinal stimulation for pain and related symptoms in multiple sclerosis: a systematic review

Background: Neuropathic and nociceptive pain frequently affect patients with multiple sclerosis (MS), with a prevalence close to 90% and significant impact on general health and quality of life. Pharmacological strategies are widely used to treat pain in MS, but their effectiveness and side-effects are controversial. Among non-pharmacological treatments for pain, non-invasive brain and spinal stimulation (NIBSS) has shown promising preliminary results in MS.Objective: Systematic review to investigate the effect of NIBSS for the management of pain in MS.Methods: A literature search using Pubmed, Science Direct and Web of Science was conducted from databases inception to February 21, 2020 for studies assessing the analgesic effect of NIBSS on pain in MS.Results: A total of 279 records were title- and abstract-screened, nine were assessed for full text and included. The NIBSS techniques explored were transcranial direct current stimulation (N = 5), transcranial magnetic stimulation (N = 2), transcranial random noise stimulation (N =1), transcutaneous spinal direct current stimulation (N = 1). The targets were the primary motor cortex (M1; N = 4), the left dorsolateral pre-frontal cortex (DLPFC; N = 3), the spinal cord (N = 1), unspecified brain target (N = 1). The study designs were randomized (N = 7), open label (N = 1), single case report (N = 1). Despite the differences in study design, target and NIBSS technique that impeded a meta-analysis, all the studies converge in showing a significant improvement of pain after active NIBSS with less consistent effects on other symptoms of the pain-related cluster (depression, fatigue, cognition) and quality of life.Conclusions: Excitatory NIBSS over M1, left DLPFC and spinal cord appear to be the most effective protocols for pain in MS. Open questions include the use of neurophysiological or neuroimaging surrogate outcome measures, the stratification of patients according to the clinical profiles and underlying pathogenetic mechanisms and the combination of NIBSS to pharmacological treatment, neurorehabilitation, or psychotherapy to improve the clinical effect. The duration of the effect to NIBSS and the feasibility and efficacy of telemedicine NIBSS protocols are other open key questions

Cognitive rehabilitation in neuro-oncological patients: three case reports

Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients, linked with morbidity, disability, and poor quality of life. As pharmacologic interventions have not yet proven effective in the treatment of cognitive deficits, cognitive rehabilitation could represent an alternative approach. This paper presents three case studies, describing the cognitive intervention and discussing its effectiveness in the light of current evidence

Telemedicine and Virtual Reality for Cognitive Rehabilitation: A Roadmap for the COVID-19 Pandemic

The current COVID-19 pandemic presents unprecedented new challenges to public health and medical care delivery. To control viral transmission, social distancing measures have been implemented all over the world, interrupting the access to routine medical care for many individuals with neurological diseases. Cognitive disorders are common in many neurological conditions, e.g., stroke, traumatic brain injury, Alzheimer's disease, and other types of dementia, Parkinson's disease and parkinsonian syndromes, and multiple sclerosis, and should be addressed by cognitive rehabilitation interventions. To be effective, cognitive rehabilitation programs must be intensive and prolonged over time; however, the current virus containment measures are hampering their implementation. Moreover, the reduced access to cognitive rehabilitation might worsen the relationship between the patient and the healthcare professional. Urgent measures to address issues connected to COVID-19 pandemic are, therefore, needed. Remote communication technologies are increasingly regarded as potential effective options to support health care interventions, including neurorehabilitation and cognitive rehabilitation. Among them, telemedicine, virtual reality, augmented reality, and serious games could be in the forefront of these efforts. We will briefly review current evidence-based recommendations on the efficacy of cognitive rehabilitation and offer a perspective on the role of tele- and virtual rehabilitation to achieve adequate cognitive stimulation in the era of social distancing related to COVID-19 pandemic. In particular, we will discuss issues related to their diffusion and propose a roadmap to address them. Methodological and technological improvements might lead to a paradigm shift to promote the delivery of cognitive rehabilitation to people with reduced mobility and in remote regions

The Multidisciplinary Approach to Alzheimer's Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment

Background: Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia.Aim: To review, with a narrative approach, current evidence on main NPTs for AD and dementia.Methods: PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers.Results: The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden.Conclusions: Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia

Differences between physician and caregiver evaluations in Alzheimer’s disease

In Alzheimer’s disease (AD) differences are often reported between caregivers’ and physicians’ aims and evaluations. The aim of this study was to investigate the presence of discrepancies between the evaluations of caregivers and physicians. Two hundred and eighteen caregivers of outpatients diagnosed with mild-to-moderate AD, referred to our Alzheimer’s Disease Assessment Unit, entered the study. Caregiver burden was investigated using the Caregiver Burden Inventory (CBI) and the Neuropsychiatric Inventory Caregiver Distress Scale (NPIDS). Caregivers were also administered a four-point scale to assess quantitatively whether their expectations in relation to the efficacy of the pharmacological treatment had been satisfied and a scale exploring clinical global impression of change. Caregivers whose expectations had not been satisfied had significantly higher CBI and NPIDS scores and a lower level of education; moreover, caregivers tended to overestimate the degree of cognitive decline during the course of the disease. These results underline the importance of correct and constant communication with AD patients and their familie

Cognitive rehabilitation in neuro-oncological patients: three case reports

Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients, linked with morbidity, disability, and poor quality of life. As pharmacologic interventions have not yet proven effective in the treatment of cognitive deficits, cognitive rehabilitation could represent an alternative approach. This paper presents three case studies, describing the cognitive intervention and discussing its effectiveness in the light of current evidence

The effects of alcohol on cognition in the elderly : from protection to neurodegeneration

The effects of chronic alcohol abuse on cognition are well known. Memory and executive functions appear to be the cognitive domains primarily impaired, and prefrontal and frontal damage is reported on neuroimaging studies both at micro- and macrostructural levels. Abstinence can partially reverse these alterations through mechanisms of neuroplasticity. Alcohol acts in a dose-dependent fashion, and a light-to-moderate consumption indeed has protective effects on cardiovascular risk factors and promotes anti-inflammatory and anti-oxidative processes. In the elderly on such a regimen, several epidemiological studies have reported a decreased risk of both coronary and cerebrovascular disease and of dementia. However, because of data heterogeneity and the presence of several confounding variables, further studies are needed to clarify these findings. In addition, the complexity of alcohol neurobiology (interaction of alcohol effects with genetic predisposition and environmental factors) and the occurrence of age-related changes should also be taken into account. As dementia, stroke and cardiovascular disease are the leading causes of mortality in older people in developed countries, a better knowledge of the mechanisms underlying the effects of alcohol intake may be helpful from the perspective not only of medical management but also of social health polic

An explorative study regarding the effect of L-deprenyl on cognitive and functional recovery in patients after stroke

INTRODUCTION: Selegiline (l-deprenyl) is a selective monoamine oxidase type B inhibitor that has been shown to have neurotrophic and anti-apoptotic properties and to protect neurons in different experimental models of cerebral ischaemia. The aim of this explorative study was to investigate whether selegiline could enhance cognitive and functional recovery in stroke survivors. METHODS: This was a randomized controlled study in which patients enrolled within two weeks of stroke underwent a clinical and functional evaluation and a neuropsychological assessment. The patients were given selegiline (10mg/day) or matched placebo once a day for six weeks in addition to standard rehabilitation care. RESULTS: Of 137 stroke survivors, 47 patients met the inclusion criteria and were randomly assigned to the Study Group (n=23) or the Control Group (n=24). The statistical analysis showed a significant improvement in most neuropsychological tests after two and six weeks in the study group; these improvements were not replicated in the control group. The between-group analysis revealed that the domains of attention and executive functions benefited most from the drug treatment. With regard to functional status, comparison of clinical scores at admission and discharge showed a statistically significant enhancement in both groups without statistically significant differences between the groups. CONCLUSIONS: These preliminary results suggest that selegiline administered in the subacute phase can promote cognitive functioning in stroke patients. Further studies will elucidate whether and how this enhancement can impact on functional recovery in the short and in the long term

Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson's disease: current evidence and future perspectives

Introduction: Non-motor symptoms (NMS) affect patients with Parkinson's disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients' and caregivers' quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need. Areas covered: The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatments of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview of ongoing trials on pharmacological and selected non-pharmacological strategies. Expert opinion: The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer's disease. Dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence on PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers