Cognitive and behavioral symptoms are common in Parkinson's disease, may occur even in the prodromal stages of the disease, worsen with disease progression, and surpass motor symptoms as the major ...factors affecting patient quality of life and caregiver burden. The symptoms may be caused by the disease pathology or they may represent adverse effects of treatment, or both etiological factors may contribute. Although many of these symptoms are related to dopaminergic dysfunction or dopaminergic medication, other neurotransmitters are involved as well. Behavioral symptoms including impulse control disorders, apathy, psychosis, as well as mild cognitive impairment and dementia are reviewed with a special focus on current treatment approaches.
•Behavioral symptoms of PD may be triggered by manipulation of dopaminergic treatment.•STN stimulation and continuous dopaminergic infusions may reduce hyperdopaminergic behaviors.•Cholinesterase inhibitors impact on cognition, behavior, and daily activities in PD-dementia.
•rTMS can produce significant clinical improvement in various neurological and psychiatric disorders.•Updated guidelines on the therapeutic use of rTMS are presented, including 2014–2018 ...publications.•Higher evidence of efficacy is present in the areas of depression, pain, and postacute motor stroke.
A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 Lefaucheur et al., Clin Neurophysiol 2014;125:2150–206. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson’s disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.
Abstract Introduction Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool for modulating cortical activity. Objectives In this pilot study, we evaluated the effects of high ...frequency rTMS applied over the right inferior frontal gyrus (IFG) on cognitive functions in patients with amnestic mild cognitive impairment (MCI) or incipient dementia due to Alzheimer's disease (AD). Methods Ten patients (6 men; 4 women, mean age of 72 ± 8 years; MMSE 23 ± 3.56) were enrolled in a randomized, placebo-controlled study with a crossover design. All participants received 2 sessions of 10 Hz rTMS over the non-dominant right hemisphere in random order: IFG (active stimulation site) and vertex (control stimulation site). Intensities were adjusted to 90% of resting motor threshold. A total of 2250 pulses were applied in a session. The Trail Making Test (TMT), the Stroop test, and the complex visual scene encoding task (CVSET) were administered before and immediately after each session. The Wilcoxon paired test was used for data analysis. Results Stimulation applied over the IFG induced improvement in the TMT parts A (p = 0.037) and B (p = 0.049). No significant changes were found in the Stroop test or the CVSET after the IFG stimulation. We observed no significant cognitive aftereffects of rTMS applied over the vertex. Conclusions High frequency rTMS of the right IFG induced significant improvement of attention and psychomotor speed in patients with MCI/mild dementia due to AD. This pilot study is part of a more complex protocol and ongoing research.
We evaluated the therapeutic effects of non-pharmacological interventions (cognitive training, physical activity, and non-invasive brain stimulation) on cognitive symptoms in Parkinson’s disease. A ...comprehensive literature search for non-pharmacological intervention randomized controlled trials was performed and effect sizes were calculated for each suitable study intervention approach and cognitive domain. Despite the heterogeneity of the study results, we report level B evidence for the probable efficacy of cognitive training in improving or maintaining attention/working memory and memory domains. Level C (possible efficacy) evidence was found for specific physical training types with respect to enhancing executive functions. Non-invasive brain stimulation techniques and combinatorial approaches show preliminary but promising results. Prediction markers evaluating distinct treatment responses should be identified that would help to choose the best candidates for specific treatment strategies and cognitive symptoms. Future directions and recommendations are discussed.
Highlights • Handwriting movements can be used to assist in the diagnosis of Parkinson's disease. • The pressure exerted on the surface during handwriting contributes to the diagnosis of PD. • A ...handwriting database containing samples from 75 PD and healthy subjects is presented.
•This review presents the contribution of TMS to the management of dementia.•TMS can be used as a biomarker of the excitability and function of cerebral cortex in dementia.•Increasing evidence ...supports the beneficial effects of rTMS in Alzheimer’s disease-related dementias at mild/early stage.
Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention.
The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment.
To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer’s disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression.
In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.
Parkinson's disease (PD) is a neurodegenerative disorder which impairs motor skills, speech, and other functions such as behavior, mood, and cognitive processes. One of the most typical clinical ...hallmarks of PD is handwriting deterioration, usually the first manifestation of PD. The aim of this study is twofold: (a) to find a subset of handwriting features suitable for identifying subjects with PD and (b) to build a predictive model to efficiently diagnose PD. We collected handwriting samples from 37 medicated PD patients and 38 age- and sex-matched controls. The handwriting samples were collected during seven tasks such as writing a syllable, word, or sentence. Every sample was used to extract the handwriting measures. In addition to conventional kinematic and spatio-temporal handwriting measures, we also computed novel handwriting measures based on entropy, signal energy, and empirical mode decomposition of the handwriting signals. The selected features were fed to the support vector machine classifier with radial Gaussian kernel for automated diagnosis. The accuracy of the classification of PD was as high as 88.13%, with the highest values of sensitivity and specificity equal to 89.47% and 91.89%, respectively. Handwriting may be a valuable marker as a diagnostic and screening tool.
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