Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease

Objective: Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods: We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory‐impaired PD (amnestic MCI; n = 9), PD with nonamnestic MCI (n = 10), PD without MCI (n = 11), and healthy controls (n = 14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results: Memory‐impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation: Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction

Imaging changes associated with cognitive abnormalities in Parkinson's disease

The current study investigates both gray and white matter changes in non-demented Parkinson's disease (PD) patients with varying degrees of mild cognitive deficits and elucidates the relationships between the structural changes and clinical sequelae of PD. Twenty-six PD patients and 15 healthy controls (HCs) were enrolled in the study. Participants underwent T1-weighted and diffusion tensor imaging (DTI) scans. Their cognition was assessed using a neuropsychological battery. Compared with HCs, PD patients showed significant cortical thinning in sensorimotor (left pre- and postcentral gyri) and cognitive (left dorsolateral superior frontal gyrus [DLSFG]) regions. The DLSFG cortical thinning correlated with executive and global cognitive impairment in PD patients. PD patients showed white matter abnormalities as well, primarily in bilateral frontal and temporal regions, which also correlated with executive and global cognitive impairment. These results seem to suggest that both gray and white matter changes in the frontal regions may constitute an early pathological substrate of cognitive impairment of PD providing a sensitive biomarker for brain changes in PD

The pill questionnaire in a nondemented Parkinson's disease population

We assessed the Pill Questionnaire as a screen for mild cognitive impairment in nondemented Parkinson's disease patients. The relationship between ability to remember medications for Parkinson's disease in the Pill Questionnaire, mild cognitive impairment, and deficits on neuropsychological tests performed 2–3 weeks later blind to Pill Questionnaire results was assessed in movement disorders clinic patients. In 109 subjects, inaccurate medication reporting on the Pill Questionnaire was associated with lower scores on the Montreal Cognitive Assessment, Scales for Outcomes in Parkinson's Disease–Cognition and with deficits in memory, attention, executive function‐inhibitory control, processing speed, visuospatial function, and language. Inaccurate medication reporting was also associated with an adjusted odds ratio of 2.4 (95% CI, 0.91–5.88; P = .06) for mild cognitive impairment, with a specificity of 80% and sensitivity of 41%. The Pill Questionnaire is neither sensitive nor specific enough to be used as the sole screening or diagnostic tool for mild cognitive impairment. However, inaccurate medication reporting is associated with deficits spanning many cognitive domains and should alert a clinician to a higher likelihood of cognitive impairment. © 2012 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93736/1/25124_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93736/2/MDS_25124_sm_SuppTables.pd

Currently Clinical Views on Genetics of Wilson′s Disease

Objective: The objective of this study was to review the research on clinical genetics of Wilson′s disease (WD). Data Sources: We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype. Study Selection: Publications about the ATP7B gene and protein function associated with clinical features were selected. Results: Wilson′s disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene ATP7B. Decreased biliary copper excretion and reduced incorporation of copper into apoceruloplasmin caused by defunctionalization of ATP7B protein lead to accumulation of copper in many tissues and organs, including liver, brain, and cornea, finally resulting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance for improving the prognosis of WD patients. However, diagnosis of this disease is usually difficult because of its complicated phenotypes. In the last 10 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction of the progression of this disease at the molecular level will aid in the development of more individualized and effective interventions, which is a key to transition from molecular genetic research to the clinical study. Conclusions: Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients

Brain tissue pulsatility is related to clinical features of Parkinson's disease

Introduction: This study investigated whether brain tissue pulsatility is associated with features of disease severity in Parkinson's disease (PD). Methods: Data were extracted from the Parkinson's Progression Markers Initiative among 81 adults with PD (confirmed with DATSCAN™). Brain tissue pulsatility was computed using resting state blood oxygenation level dependent (BOLD) MRI in white matter (WM), referred to as BOLDTP. Motor impairment was assessed using the Movement Disorders Society unified Parkinson's disease rating scale. Factor analysis generated composite scores for cognition and vascular risk burden. A linear regression model examined the association of BOLDTP with age, sex, motor impairment, cognition, vascular risk burden and PD duration. In addition, we investigated whether BOLDTP relates to WM hyperintensity (WMH) volume, WM fractional anisotropy (WM-FA) and striatal binding ratio (SBR) of dopamine transporter. Results: Motor impairment (t = 2.3, p = .02), vascular burden (t = 2.4, p = .02) and male sex (t = 3.0, p = .003) were independently associated with BOLDTP (r2 = 0.40, p  .1). In addition, BOLDTP (t = 2.76, p = .008) and SBR (t = −2.04, p = .04) were independently related to motor impairment (r2 = 0.18, p = .006). Conclusion: Our findings show that brain tissue pulsatility from BOLD images in WM is related to neurological and vascular features in PD. BOLDTP may be useful in PD to study small vessel alterations that appear distinct from WM structural changes. Keywords: Brain tissue pulsatility, Parkinson's disease, White matter, Vascular risk factors, Blood oxygenation level dependent MR

Medical Management of Parkinson's Disease after Initiation of Deep Brain Stimulation

In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate). As for the psychiatric problems so frequently reported in PD patients, researchers have directed their attention to the complex interplay between stimulation and reduction of dopaminergic drugs only recently. In conclusion, studies addressing medical management following DBS are still needed and will certainly contribute to the ultimate success of DBS procedures

Parkinson disease with mild cognitive impairment: Domain-specific cognitive complaints predict dementia.

BackgroundThe presence of subjective cognitive complaints (SCC) as a predictor of cognitive impairment in Parkinson´s disease (PD) has shown conflicting results. Most previous studies only assessed complaints in the memory domain. We investigate the association of SCCs across cognitive domains with development of mild cognitive impairment (PD-MCI) and dementia (PDD) in PD and to assess agreement between SCCs and objective cognitive impairments in this population.MethodsThis is a retrospective analysis of a prospective cohort study. Participants were enrolled at six North-American movement disorders centers. They underwent neuropsychological and non-cognitive clinical evaluations, including the modified Neurobehavioral Inventory to elicit SCC (rated by each patient and independently by their close contact (CC)). Associations between SCCs and development of future cognitive impairment were assessed. Agreement between SCCs and objective impairment within the same domain was also calculated.ResultsOf 138 included PD patients, 42% fulfilled criteria for PD-MCI. None of the NBI items predicted development of cognitive impairment after one and two years in PD with normal cognition. In PD-MCI patients, SCCs related to attention predicted dementia at year one. CC ratings of SCCs related to memory and language problems predicted PDD in PD-MCI patients. According to CC reported patients' complaints, there was a significant agreement between SCCs and objective cognitive test scores on attention.ConclusionsEliciting SCCs including cognitive domains other than memory is crucial for a complete evaluation, including both patient and CC report. Memory, language, and especially attention SCCs in PD-MCI may predict progression to dementia

Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease

Objective: Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods: We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory‐impaired PD (amnestic MCI; n = 9), PD with nonamnestic MCI (n = 10), PD without MCI (n = 11), and healthy controls (n = 14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results: Memory‐impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation: Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction

A comparison of the mini mental state exam to the Montreal cognitive assessment in identifying cognitive deficits in Parkinson's disease

Dementia is an important and increasingly recognized problem in Parkinson's disease (PD). The mini-mental state examination (MMSE) often fails to detect early cognitive decline. The Montreal cognitive assessment (MoCA) is a brief tool developed to detect mild cognitive impairment that assesses a broader range of domains frequently affected in PD. The scores on the MMSE and the MoCA were compared in 88 patients with PD. A pronounced ceiling effect was observed with the MMSE but not with the MoCA. The range and standard deviation of scores was larger with the MoCA(7-30, 4.26) than with the MMSE(16-30, 2.55). The percentage of subjects scoring below a cutoff of 26/30 (used by others to detect mild cognitive impairment) was higher on the MoCA (32%) than on the MMSE (11%)(P <0.000002). Compared to the MMSE, the MoCA may be a more sensitive tool to identify early cognitive impairment in PD. (C) 2007 Movement Disorder Societ