PD-related Dementia Research Articles

Mild cognitive impairment in patients with Parkinson´s disease and the analysis of associated factors

ABSTRACT Objectives This research targeted to understand the impact of clinical findings, non-motor symptoms, white matter hyperintensities (WMHs), and metabolic features on cognition in Parkinson’s disease patients with mild cognitive impairment (PD-MCI). Methods Sixty-one PD patients sundered into two groups: PD-MCI and normal cognition (PD-NC). We assessed cognition using Montreal Cognitive Assessment-TR (MoCA-TR) and Frontal Assessment Battery (FAB). We used the modified Hoehn&Yahr staging scale (mH&Y), Unified Parkinson’s Disease Rating Scale (UPDRS), Freezing of Gait questionnaire, Beck Depression Inventory, Parkinson’s disease sleep scale-2, Pittsburgh sleep quality index, Epworth sleepiness scale, and Non-motor symptoms questionnaire to evaluate all patients. We used the Fazekas scale to evaluate the WMHs and also investigated all laboratory parameters affecting cognitive functions. Results Duration of disease, UPDRS-Motor part, age, disease stage, and daytime sleepiness were dramatically higher in the PD-MCI group than in PD-NC (p < 0.05). WMHs and homocysteine were higher in the PD-MCI group than in the controls (p = 0.016 and p < 0.001, respectively). There was a negative correlation between cognition and duration of disease, age, disease stage, UPDRS-Motor scale, daytime drowsiness, WMHs and homocysteine levels. Homocysteine was negatively related to visuospatial/executive functions (r=-0.303, p = 0.021). WMHs were correlated with global cognition (p =.000 r = .-542), language (p = .001, r = -.434), and delayed recall (p = .011, r = -.332). Discussion Mild cognitive impairment is a widespread clinical situation of PD patients and often presents before the motor symptoms. Revealing curable causes that affect cognition before the development of PD-related dementia is crucial in controlling motor findings and reducing the burden of the caretakers.

Midsagittal corpus callosal thickness and cognitive impairment in Parkinson's disease

People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts. The objective of this project was thus twofold: First, we investigated possible changes in the thickness of the midsagittal callosum and cortex in patients with PD with varying levels of cognitive impairment; and secondly, we investigated the relationship between the thickness of the midsagittal corpus callosum and the thickness of the cortex. Study participants included cognitively unimpaired PD participants (n = 35), PD participants with mild cognitive impairment (n = 22), PD participants with dementia (n = 17) and healthy controls (n = 27). We found thinning of the callosum in PD‐related dementia compared with PD‐related mild cognitive impairment and cognitively unimpaired PD participants. Regression analyses found thickness of the left medial orbitofrontal cortex to be positively correlated with thickness of the anterior callosum in PD‐related mild cognitive impairment. This study suggests that a midsagittal thickness model can uncover changes to the corpus callosum in PD‐related dementia, which occur in line with changes to the cortex in this advanced disease stage.

Deep brain stimulation in Alzheimer's disease.

Benefits from symptomatic and etiologic treatments in Alzheimer's Disease (AD), the most frequent dementia, are still insufficient. During the last decade, several studies showed that electrical stimulation of memory circuits could enhance memory in humans without memory impairment. First, improvement of verbal recollection was reported after deep brain stimulation (DBS) of the fornix in the hypothalamus in a patient treated for morbid obesity. Several studies in epileptic patients explored by deep electrodes reported that visuo-spatial memorization was facilitated by electrical stimulation of the entorhinal cortex or theta burst stimulation of the fornix. Recent studies suggested that DBS could be useful to modulate memory circuits in patients with cognitive decline. Phase I and II studies (about 50 patients) showed that chronic fornix DBS was safe and could achieved to stabilize or slow the memory decline of some patients with mild to moderate AD, especially older ones with less severe and/or advanced disease. DBS of the cholinergic nucleus of Meynert also has been explored in phase I studies in AD and Parkinson-related dementia. Growing experimental data suggest several mechanisms of action: restoration of hippocampal theta rhythms, enhanced long term potentiation, increase of hippocampal neurogenesis, neuroprotection by release of neurotrophic factors, diffuse reactivation of hypoactive neocortical associative regions. However, DBS in AD is still investigational and numerous issues remain to be solved before envisaging its use in clinical practice, including optimal anatomical DBS target, stimulation modalities (continuous, intermittent, theta-bursts, closed loop stimulation), best candidate patients, relevant targeted symptoms, ethical considerations.

Biological Sex and Sex Hormone Impacts on Deficits in Episodic-Like Memory in a Rat Model of Early, Pre-motor Stages of Parkinson's Disease.

Episodic memory deficits are among the earliest appearing and most commonly occurring examples of cognitive impairment in Parkinson's disease (PD). These enduring features can also predict a clinical course of rapid motor decline, significant cognitive deterioration, and the development of PD-related dementia. The lack of effective means to treat these deficits underscores the need to better understand their neurobiological bases. The prominent sex differences that characterize episodic memory in health, aging and in schizophrenia and Alzheimer's disease suggest that neuroendocrine factors may also influence episodic memory dysfunction in PD. However, while sex differences have been well-documented for many facets of PD, sex differences in, and sex hormone influences on associated episodic memory impairments have been less extensively studied and have never been examined in preclinical PD models. Accordingly, we paired bilateral neostriatal 6-hydroxydopamine (6-OHDA) lesions with behavioral testing using the What-Where-When Episodic-Like Memory (ELM) Task in adult rats to first determine whether episodic-like memory is impaired in this model. We further compared outcomes in gonadally intact female and male subjects, and in male rats that had undergone gonadectomy—with and without hormone replacement, to determine whether biological sex and/or sex hormones influenced the expression of dopamine lesioned-induced memory deficits. These studies showed that 6-OHDA lesions profoundly impaired recall for all memory domains in male and female rats. They also showed that in males, circulating gonadal hormones powerfully modulated the negative impacts of 6-OHDA lesions on What, Where, and When discriminations in domain-specific ways. Specifically, the absence of androgens was shown to fully attenuate 6-OHDA lesion-induced deficits in ELM for “Where” and to partially protect against lesion-induced deficits in ELM for “What.” In sum, these findings show that 6-OHDA lesions in rats recapitulate the vulnerability of episodic memory seen in early PD. Together with similar evidence recently obtained for spatial working memory, the present findings also showed that diminished androgen levels provide powerful, highly selective protections against the harmful effects that 6-OHDA lesions have on memory functions in male rats.

COGTIPS: a double-blind randomized active controlled trial protocol to study the effect of home-based, online cognitive training on cognition and brain networks in Parkinson\u2019s disease

BackgroundCognitive dysfunction is highly prevalent in Parkinson’s disease (PD) and a large proportion of patients eventually develops PD-related dementia. Currently, no effective treatment is available. Cognitive training is effective in relieving cognitive dysfunctions in several –neurodegenerative– diseases, and earlier small-scale trials have shown positive results for PD. In this randomized controlled trial, we assess the efficacy of online home-based cognitive training, its long-term effects, as well as the underlying neural correlates in a large group of PD patients.MethodsIn this double-blind randomized controlled trial we will include 140 non-demented patients with idiopathic PD that experience significant subjective cognitive complaints. Participants will be randomized into a cognitive training group and an active control group. In both groups, participants will individually perform an online home-based intervention for eight weeks, three times a week during 45 min. The cognitive training consists of thirteen games that focus on executive functions, attention and processing speed with an adaptive difficulty. The active control comprises three games that keep participants cognitively engaged without a training component. Participants will be subjected to extensive neuropsychological assessments at baseline and after the intervention, and at six months, one year and two years of follow-up. A subset of participants (40 in each treatment condition) will undergo structural and functional magnetic resonance imaging. The primary outcome of this study is the performance on the Tower of London task. Secondary outcomes are objective and subjective cognitive functioning, conversion to PD-related mild cognitive impairment or dementia, functional and structural connectivity and network topological indices measured with magnetic resonance imaging. None of the outcome measures are part of the cognitive training program. Data will be analyzed using multivariate mixed-model analyses and odds ratios.DiscussionThis study is a large-scale cognitive training study in PD patients that evaluates the efficacy in relieving cognitive dysfunction, and the underlying mechanisms. The strengths of this study are the large sample size, the long follow-up period and the use of neuroimaging in a large subsample. The study is expected to have a low attrition and a high compliance rate given the home-based and easily-accessible intervention in both conditions.Trial registrationClinicalTrials.gov ID NCT02920632. Registered September 30, 2016.

Mild cognitive impairment in Parkinson's disease: Characterization and impact on quality of life according to subtype.

Mild cognitive impairment (MCI) was initially described as a risk factor for Alzheimer's disease. Because of differences in baseline cognitive abilities, MCI in Parkinson's disease (PD; PD-MCI) requires distinct neuropsychological criteria for diagnosis and follow up. In addition to representing a risk factor for PD-related dementia, PD-MCI results in higher morbidity, which can be reduced through early detection. The aim of the present study was to gather data regarding MCI subtypes from neuropsychological profiles and clinical features in PD patients, to evaluate its impact on patients' quality of life according to subtype, and to compare the data with a control (Co) group. A total of 149 individuals were selected: 81 controls and 60 patients diagnosed with PD according to the United Kingdom Parkinson's Disease Society Brain Bank criteria. All individuals were submitted to neurological and neuropsychological assessments. The amnestic subtype of MCI was the most common in both the PD and Co groups. PD patients showed greater impairment in MCI than the Co group. The amnestic subtype of PD-MCI was associated with a lower quality of life compared with the non-amnestic group. The PD group showed worse cognitive performance than the Co group. The amnestic subtype of PD-MCI was associated with the greatest impairment of quality of life. Geriatr Gerontol Int 2019; 19: 497-502.

Clinical profile of early-onset dementia from a geriatric clinic in South India

Background: Early-onset dementia (EOD) defined as dementia with clinical onset before the age of 65 years, has estimated proportion ranging up to 45.3%. Although EOD leads to severe psychosocial consequences that affect people in their latter part of working age, the literature from India is limited. Objective: The aim of this study is to investigate the profile of patients with EOD attending Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India. Materials and Methodology: All records of patients attending the Geriatric Clinic and Services, diagnosed with EOD between January 2017 and June 2018 with their details pertaining to sociodemographic, clinical, risk factors, and behavioral problems were examined. Results: Of the 320 patients with cognitive complaints seen during the period of 18 months, 108 (33.75%) patients had a diagnosis of EOD. The mean age at onset of illness was 55.38 (Standard deviation - 6.53) years (range - 34–65 years). Of these 58 (53.6%) patients found to have Alzheimer's dementia (AD), 31 (28.7%) have fronto-temporal dementia (FTD), 6 (5.5%) have vascular dementia (VaD), 3 (2.7%) patients have Parkinson's disease-related dementia, and 6 (5.5%) have unspecified dementia. Discussion: During the 18 months, the EOD patients constituted one-third of all dementia patients visiting Geriatric Clinic. Degenerative etiology was the main diagnostic cluster. The most common type was AD, similar to senile type of dementia, was followed by FTD and VaD. The study showed a delay of 3.18 years in seeking consultation. Conclusion: EODs seems to have higher degenerative etiology and with higher associated behavioral and psychological symptoms. There is a need for setting up specialized memory clinics.

Association between clusterin concentration and dementia: a systematic review and meta-analysis.

Studies have showed that high clusterin (CLU) concentration was associated with increased risk of dementia. However, the results based on small samples remained controversial. The aim of our study was to determine the relationship between CLU concentration and the late-life cognitive outcomes including mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease related dementia (PDD), Lewy body dementia (DLB) and frontotemporal dementia (FTD). A comprehensive search was conducted to screen the eligible studies in online database PubMed, Web of Science and Embase from 1950 to January 2017 according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. The CLU concentration data in brain tissue, cerebrospinal fluid (CSF), serum and plasma was collected to determine the strength of this association. The results were presented with standard difference of the mean (SDM) with 95% confidence intervals (CIs). A total of 28 studies were identified to calculate the association between CLU concentration and dementia. The results showed that the CLU concentration in the plasma (SDM = 0.73, 95% CI 0.26-1.19, P = 0.002) and brain tissue (SDM = 0.71, 95% CI 0.10-1.32, P = 0.022) was increased in dementia compared to normal control. Subgroup analysis showed that the plasma CLU concentration was significantly increased only in the AD group (SDM = 1.85, 95% CI 0.84-2.85, P < 0.001), but not in MCI or other dementias. No association was found between serum and CSF clusterin concentration and dementia. This meta-analysis indicates that high CLU concentration in the plasma and brain is associated with dementia, especially in AD.

Multidimensional Care Burden in Parkinson-Related Dementia.

Providing care to people with Parkinson-related dementia (PwPRD) may result in significant stress, strain, and burden for life partners. A common measurement of life partner burden is the Zarit Burden Interview (ZBI), which considers "burden" as a unitary concept; however, burden is highly complex and most likely comprises several dimensions. This study aimed to explore the factor structure of the ZBI in life partners of PwPRD and to examine the relationships among the emerging factors and the demographic and clinical features. Life partners of PwPRD participated in home-based quantitative assessments and self-completed postal questionnaires. The assessment battery included ZBI, measures of relationship satisfaction, mood, stress, resilience, health, quality of life, feelings related to care provision, and sociodemographic questions. Data on PwPRDs' motor and neuropsychiatric symptom severity were also elicited in home-based assessments. An exploratory factor analysis (principal axis factoring) of ZBI, conducted with 127 life partners, revealed five burden dimensions: social and psychological constraints, personal strain, interference with personal life, concerns about future, and guilt. These burden factors were associated with lower relationship satisfaction, mental health, and resilience, and higher stress, anxiety, depression, resentment, negative strain, and PwPRD motor severity. In multiple linear regression analyses, where each factor score was the dependent variable, stress, negative strain, and resentment emerged as significant predictors of specific burden dimensions. Burden is a complex and multidimensional construct. Interventions should address specific types of burden among life partners of PwPRD to support couples' relationships and maintain quality of life.

Psychosocial therapy for Parkinson's-related dementia: intervention development.

BackgroundGroup-based psychosocial therapy, such as group Cognitive Stimulation Therapy, improves cognition and quality of life in people living with dementia. Neuropsychiatric symptoms and restricted mobility are common complications for people with Parkinson’s-related dementia (PRD) and may limit access to, and participation in, group activities. This study describes the development of a condition-specific, home-based psychosocial therapy for people with PRD ready to be trialled in a clinical population.MethodsBy means of a multistage process, a draft therapy manual was developed in an iterative manner through collaboration with medical experts, researchers and Patient and Public Involvement (PPI) representatives. In stage 1, an extensive literature search of psychosocial therapies for dementia with potential relevance for Parkinson’s disease (PD) was undertaken to select a candidate therapy for adaptation. In stage 2, qualitative feedback from stakeholders and intelligence regarding existing nonpharmacological therapies for cognitive impairment in PD was combined to produce a prototype therapy manual. In stage 3, the manual was field tested in: 1) a home-setting using a 25-item assessment tool; and 2) at a local PD support group with PPI representatives. Based on the feedback from this phase, final design modifications were implemented and a draft therapy manual produced.ResultsThe manual was developed in an iterative manner. Interview and focus group transcripts identified three enduring themes: manual form and content, therapy acceptability by people with PRD, and companion guidance and support. Major adaptations included: removal of discrete levels of task complexity, removal of images that were potentially hallucinogenic or lacked clarity, and updating of the content.ConclusionWe have successfully developed a Cognitive Stimulation Therapy-based psychosocial therapy specifically adapted for people with PRD. The therapy is ready to trial in a pilot randomized controlled study.

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease

Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood. Classically, mitochondrial dysfunction has been viewed as the major source of oxidative stress and has been shown to precede tau and amyloid pathology in various dementias, but the exact mechanisms are not clear. It is known that the production of ROS by mitochondria can result in ultraweak photon emission (UPE) within cells. While of low intensity, surrounding proteins within the cytosol can still absorb these energetic photons via aromatic amino acids (e.g., tryptophan and tyrosine). One likely absorber of these photons is the microtubule cytoskeleton, as it forms a vast network spanning neurons, is highly co-localized with mitochondria, and shows a high density of aromatic amino acids. Functional microtubule networks may traffic this ROS-generated endogenous photon energy for cellular signaling, or they may serve as dissipaters/conduits of such energy to protect the cell from potentially harmful effects. Experimentally, after in vitro exposure to exogenous photons, microtubules have been shown to reorient and reorganize in a dose-dependent manner with the greatest effect being observed around 280nm, in the tryptophan and tyrosine absorption range. In this paper, recent modeling efforts based on ambient temperature experiment are presented, showing that tubulin polymers can feasibly absorb and channel these photoexcitations via resonance energy transfer, on the order of dendritic length scales and neuronal fine structure. Since microtubule networks are compromised in tauopathic diseases such as Alzheimer's and Parkinson's dementias, patients with these illnesses would be unable to support effective channeling of these photons for signaling or dissipation. Consequent emission surplus due to increased UPE production or decreased ability to absorb and transfer may lead to increased cellular oxidative damage, thus hastening the neurodegenerative process.

Clinical Spectrum, Risk Factors, and Behavioral Abnormalities among Dementia Subtypes in a North Indian Population: A Hospital-Based Study

Background: As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. Methods: We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investigations, and follow-up of 1,876 patients with dementia (PwD), and the data were analyzed using descriptive statistics. Results: Of the total PwD, Alzheimer disease (AD) accounted for 30% followed by vascular dementia (VaD) 26%, mixed dementia (MD) 21%, Parkinson-related dementia 11%, frontotemporal dementia (FTD) 7%, and infective dementia 5%. Of all PwD excluding the infective group (n = 1,777), 63% were men, 39% were from rural areas, 87% had behavioral abnormalities along with cognitive deficits, and 73% had impaired ADLs. Among dementia subtypes, a positive family history, cardiovascular and metabolic risk factors, and behavioral abnormalities were found to be distributed. However, there existed a predominance of specific behavioral pattern in each subtype. The mean duration of follow-up varied from 2.9 ± 2.3 (VaD) to 3.6 ± 2.1 (AD) and greater than 30% were found to be stable on treatment (except in dementia with Lewy body). Conclusions: This large hospital-based study provides a distribution pattern and clinical spectrum of dementia subtypes in a North Indian population.

Psychosocial therapy for Parkinson's-related dementia: study protocol for the INVEST randomised controlled trial

IntroductionParkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and ‘non-motor’ symptoms which impact on quality of life....

Diagnosing mild cognitive impairment in Parkinson's disease: which tests perform best in the Italian population?

Mild cognitive impairment (MCI) is common in patients with Parkinson's disease (PD) and should be recognized early because it represents a predictor of PD-related dementia and worse disease course. Diagnostic criteria for PD-related MCI (PD-MCI) have recently been defined by a Movement Disorders Society (MDS) task force. The present study explored which neuropsychological tests perform best for a level II (i.e., comprehensive neuropsychological assessment) diagnosis of PD-MCI according to the MDS task force criteria in Italian-speaking PD patients. To this aim, we assessed a comprehensive 23-item neuropsychological battery, derived the best-performing 10-test battery (i.e., two tests per domain for each of the five cognitive domains), and explored its accuracy for diagnosing PD-MCI in comparison to the full battery in a group of PD patients. A secondary aim was to explore the role of this battery for subtyping PD-MCI according to single-domain vs. multiple-domain involvement. The 10-test battery showed 73% sensitivity and 100% specificity for diagnosing PD-MCI, and 69% sensitivity and 100% specificity for PD-MCI subtyping. In patients older than 70years, we derived a slightly different 10-test battery with 84% sensitivity and 100% specificity for PD-MCI diagnosis, and 86% sensitivity and 100% specificity for PD-MCI subtyping. These 10-item neuropsychological batteries might represent a good trade-off between diagnostic accuracy and time of application, and their role in PD-MCI diagnosis and subtyping should be further explored in future prospective studies.

Serum Butyrylcholinesterase Activity: A Biomarker for Parkinson's Disease and Related Dementia.

Objective This study aim to determine changes of serum butyrylcholinesterase (BChE) activity in PD patients and related dementia. Patients and Methods Consecutive PD patients and healthy controls were included and clinical data were collected. Fast serum BChE activity was determined and compared between healthy controls and PD patients. Independent risk factors were performed for BChE activity, PD, and related dementia. The relationship between BChE activity and disease severity was also evaluated. Receiver operating characteristic (ROC) curves were obtained to explore serum BChE activity in distinguishing PD patients and related dementia. Results Serum BChE activity mainly independently correlated with gender, albumin, triglyceride, body mass index, and PD. Serum BChE activity decreased in PD patients compared with healthy controls. Based on the ROC curve, the optimal cut-off point was 6864.08 IU/L for distinguishing PD patients, and the sensitivity and specificity values were 61.8% and 72.1%. It inversely correlated with Unified Parkinson's Disease Rating Scale score. BChE activity decreased in PD-related dementia compared with those without dementia. The sensitivity and specificity values were 70.6% and 76.3%, respectively, with an optimal cut-off point of 6550.00 IU/L. Conclusions Serum BChE activity can be regarded as a biomarker for PD and related dementia.

Small Molecule-Assisted PET: Approaches to Imaging of Conformational Diseases of the Brain

PET (positron emission tomography) in vivo imaging of cerebral conformational diseases is essentially based on non-peptide small molecule ligands used to detect early alterations in peptide secondary structures and subsequent accumulation of aberrant oligomers and protein deposits involved in progressive neurodegeneration, cognitive and movement disorders. In this article, an overview is given about tracers currently available and lead structures of potential PET probes for detection of β-amyloid (Aβ), tau protein, α-synuclein, constitutive (PrPc) and infectious isoforms (PrPsc) of prions (proteinaceous infectious particles) as imaging targets. Whereas the styrylpyridine derivative florbetapir, approved for clinical applications, the stilbene derivative florbetaben and the benzoxazole derivative BF227 show high affinity binding to Aβ, preclinical investigations promise improved pharmacokinetics for benzoimidazothiazoles, aryloxazoles and benzofuran derivatives. Tau protein imaging based clinically, presently, on the pyridine-pyridoindole T807 has got new incentives following identification of a series of pyrrolopyridine quinolines and pharmacokinetic improvements of fluoropropoxy quinolines including for instance THK-5351. The pyridine isoquinoline MK6240 is involved now in clinical trials. Most forward-looking efforts apply to small molecule ligands of α-synuclein, which are expected to permit a breakthrough in differential diagnostics of Parkinson-related dementia and Lewy body diseases. However, at the moment the proposed lead structures are in affinity and blood brain barrier delivery properties below the possibilities of Aβ and tau protein ligands. This is the case also for potential tracers of prion proteins.

Quantitative EEG and Cognitive Decline in Parkinson's Disease.

Cognitive decline is common with the progression of Parkinson's disease (PD). Different candidate biomarkers are currently studied for the risk of dementia in PD. Several studies have shown that quantitative EEG (QEEG) is a promising predictor of PD-related cognitive decline. In this paper we briefly outline the basics of QEEG analysis and analyze the recent publications addressing the predictive value of QEEG in the context of cognitive decline in PD. The MEDLINE database was searched for relevant publications from January 01, 2005, to March 02, 2015. Twenty-four studies reported QEEG findings in various cognitive states in PD. Spectral and connectivity markers of QEEG could help to discriminate between PD patients with different level of cognitive decline. QEEG variables correlate with tools for cognitive assessment over time and are associated with significant hazard ratios to predict PD-related dementia. QEEG analysis shows high test-retest reliability and avoids learning effects associated with some neuropsychological testing; it is noninvasive and relatively easy to repeat.

Wavelet Energy and Wavelet Coherence as EEG Biomarkers for the Diagnosis of Parkinson’s Disease-Related Dementia and Alzheimer’s Disease

Parkinson’s disease (PD) and Alzheimer’s disease (AD) can coexist in severely affected; elderly patients. Since they have different pathological causes and lesions and consequently require different treatments; it is critical to distinguish PD-related dementia (PD-D) from AD. Conventional electroencephalograph (EEG) analysis has produced poor results. This study investigated the possibility of using relative wavelet energy (RWE) and wavelet coherence (WC) analysis to distinguish between PD-D patients; AD patients and healthy elderly subjects. In EEG signals; we found that low-frequency wavelet energy increased and high-frequency wavelet energy decreased in PD-D patients and AD patients relative to healthy subjects. This result suggests that cognitive decline in both diseases is potentially related to slow EEG activity; which is consistent with previous studies. More importantly; WC values were lower in AD patients and higher in PD-D patients compared with healthy subjects. In particular; AD patients exhibited decreased WC primarily in the γ band and in links related to frontal regions; while PD-D patients exhibited increased WC primarily in the α and β bands and in temporo-parietal links. Linear discriminant analysis (LDA) of RWE produced a maximum accuracy of 79.18% for diagnosing PD-D and 81.25% for diagnosing AD. The discriminant accuracy was 73.40% with 78.78% sensitivity and 69.47% specificity. In distinguishing between the two diseases; the maximum performance of LDA using WC was 80.19%. We suggest that using a wavelet approach to evaluate EEG results may facilitate discrimination between PD-D and AD. In particular; RWE is useful for differentiating individuals with and without dementia and WC is useful for differentiating between PD-D and AD.

Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments.

Modern deep brain stimulation (DBS) has become a routine therapy for patients with movement disorders such as Parkinson's disease, generalized or segmental dystonia and for multiple forms of tremor. Growing numbers of publications also report beneficial effects in other movement disorders such as Tourette's syndrome, various forms of chorea and DBS is even being studied for Parkinson's-related dementia. While exerting remarkable effects on many motor symptoms, DBS does not restore normal neurophysiology and therefore may also have undesirable side effects including speech and gait deterioration. Furthermore, its efficacy might be compromised in the long term, due to progression of the underlying disease. Various programming strategies have been studied to try and address these issues, e.g., the use of low-frequency rather than high-frequency stimulation or the targeting of alternative brain structures such as the pedunculopontine nucleus. In addition, further technical developments will soon provide clinicians with an expanded choice of hardware such as segmented electrodes allowing for a steering of the current to optimize beneficial effects and reduce side effects as well as the possibility of adaptive stimulation systems based on closed-loop concepts with or without accompanying advances in programming and imaging software. In the present article, we will provide an update on the most recent achievements and discoveries relevant to the application of DBS in the treatment of movement disorder patients and give an outlook on future clinical and technical developments.

Status of treatment for dementia patients who visited hospital as the first visit

We are approaching a period of population ageing in which the number of dementia patients will increase rapidly and become a significant social problem. There are many study guides for treatment of dementia, but there are limited numbers of studies and limited amounts of data available for evaluating the treatment used on dementia patients as related to their hospital for the first time. A study was performed using information gathered from 50 domestic hospitals to ensure that the treatment status data was representative of the actual field of clinical dementia. We observed retrospectively the medical records of 4282 patients who visited the hospital and were finally judged to have dementia from January, 2009 to December, 2010. Among the types of dementia, Alzheimer's disease (AD) had the greatest occurrence at 66.57%, with vascular dementia (VD) at 17.63%, AD with CVD at 10.18%, and Parkinson related dementia at 4.25%. The drug primarily used for initial therapy is the same drug primarily used for patients who have undergone long term dementia treatment, namely donepezil (75.22%). Among all 4282 patients, there was addition or transition of drugs used for 389 of the patients. Ineffectiveness of the initial drug treatment was the reason for the addition of drugs or transition to other drugs in almost all cases. In this study, the clinical characteristics observed for dementia treatment is compared as drugs changing, which will be helpful in the preparation of a treatment guide for dementia in the future.