Effects of dopaminergic depletion and brain atrophy on neuropsychiatric symptoms in de novo Parkinson’s disease

BackgroundNeuropsychiatric symptoms impact the patients’ quality of life and caregivers’ burdens in Parkinson’s disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD.MethodsTwo hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients’ neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders.ResultsFrontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score.ConclusionsThe results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.

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Dopaminergic and Serotonergic Degeneration and Cortical [ 18 F ]Fluorodeoxyglucose Positron Emission Tomography in De Novo Parkinson's Disease

Movement Disorders ◽

10.1002/mds.28654 ◽

2021 ◽

Author(s):

Beatrice Orso ◽

Dario Arnaldi ◽

Nicola Girtler ◽

Andrea Brugnolo ◽

Elisa Doglione ◽

...

Keyword(s):

Parkinson’S Disease ◽

Positron Emission Tomography ◽

Parkinson's Disease ◽

De Novo ◽

Emission Tomography ◽

Fluorodeoxyglucose Positron Emission Tomography ◽

Positron Emission ◽

Fluorodeoxyglucose Positron Emission

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Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson’s Disease Is Modified by the SNCA rs356181 Polymorphism

Neurodegenerative Diseases ◽

10.1159/000493103 ◽

2018 ◽

Vol 18 (5-6) ◽

pp. 233-238

Author(s):

Frederic Sampedro ◽

Juan Marín-Lahoz ◽

Saul Martínez-Horta ◽

Javier Pagonabarraga ◽

Jaime Kulisevsky

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Decline ◽

De Novo ◽

Brain Regions ◽

Cortical Atrophy ◽

Csf Biomarkers ◽

Gene Encoding ◽

Cortical Thinning ◽

Age Related

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson’s disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson’s Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP’s genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.

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White Matter Hyperintensities and Cognitive Decline in de Novo Parkinson’s Disease Patients

10.1101/230896 ◽

2017 ◽

Author(s):

Mahsa Dadar ◽

Yashar Zeighami ◽

Yvonne Yau ◽

Seyed-Mohammad Fereshtehnejad ◽

Josefina Maranzano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

De Novo ◽

Cognitive Test ◽

Cortical Thinning

AbstractObjectiveWhite Matter Hyperintensities (WMHs) are associated with cognitive decline in normative aging and Alzheimer’s disease. However, the pathogenesis of cognitive decline in Parkinson’s disease (PD) is not directly related to vascular causes, and therefore the role of WMHs in PD remains unclear. If WMH has a higher impact on cognitive decline in PD, vascular pathology should be assessed and treated with a higher priority in this population. Here we investigate whether WMH leads to increased cognitive decline in PD, and if these effects relate to cortical thinningMethodsTo investigate the role of WMHs in PD, it is essential to study recently-diagnosed/non-treated patients.De novoPD patients and age-matched controls (NPD=365,NControl=174) with FLAIR/T2-weighted scans at baseline were selected from Parkinson’s Progression Markers Initiative (PPMI). WMHs and cortical thickness were measured to analyse the relationship between baseline WMHs and future cognitive decline (follow-up:4.09±1.14 years) and cortical thinning (follow-up:1.05±0.10 years).ResultsHigh WMH load (WMHL) at baseline in PD was associated with increased cognitive decline, significantly more than i) PDs with low WMHL and ii) controls with high WMHL. Furthermore, PD patients with higher baseline WMHL showed more cortical thinning in right frontal lobe than subjects with low WMHL. Cortical thinning of this region also predicted decline in performance on a cognitive test.InterpretationPresence of WMHs inde novoPD patients predicts greater future cognitive decline and cortical thinning than in normal aging. Recognizing WMHs as a potential predictor of cognitive deficit in PD provides an opportunity for timely interventions.

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Decision letter: Network structure of brain atrophy in de novo Parkinson's disease

10.7554/elife.08440.021 ◽

2015 ◽

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Network Structure ◽

Brain Atrophy ◽

De Novo

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Author response: Network structure of brain atrophy in de novo Parkinson's disease

10.7554/elife.08440.022 ◽

2015 ◽

Cited By ~ 1

Author(s):

Yashar Zeighami ◽

Miguel Ulla ◽

Yasser Iturria-Medina ◽

Mahsa Dadar ◽

Yu Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Network Structure ◽

Brain Atrophy ◽

De Novo ◽

Author Response ◽

Response Network

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Abstract P721: Parkinson’s Disease Patients With Ischemic Stroke Have Shorter Hospital Stay Compared to Those Without Parkinson’s Disease: A National Inpatient Sample Study 1998-2017

Stroke ◽

10.1161/str.52.suppl_1.p721 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Veronica Moreno Gomez ◽

Maria Shoaib ◽

Muhammad Farhan Khaliq ◽

Chao Xu ◽

Timothy Copeland ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ischemic Stroke ◽

Length Of Stay ◽

Hospital Stay ◽

Negative Binomial ◽

Negative Binomial Regression ◽

Disease Status ◽

Prior History ◽

History Of

Introduction: A paucity of studies exists about the influence of Parkinson’s Disease (PD) in the length of stay (LOS) among patients admitted with acute ischemic stroke (AIS). We seek to identify if a prior history of PD impacts the LOS of AIS patients, and to establish the factors associated it. Methodology: We analyzed data of the NIS from the Healthcare Cost and Utilization Project (HCUP) from 1998 to 2017, using a negative binomial regression to assess sociodemographic factors and hospital characteristics associated with LOS in AIS patients with PD. Results: A total of 835,380,672 hospitalizations were identified with discharge diagnosis of AIS. The cohort was divided into 2 groups based on presence of history of PD during the same admission. 12,799,437 of AIS patients had discharge records with a secondary diagnosis of PD. Non-Parkinson’s disease cohort had longer hospital stay (Incidence Rate Ratio IRR 1.02 (95% CI 1.01-1.03). An increased LOS was observed in males compared to females (IRR 1.03 (1.00-1.03)); Black (IRR 1.17 (95% CI 1.16-1.18)), Hispanics (IRR 1.13 (95% CI 1.11-1.14)) and Asians (IRR 1.22 (95% CI 1.19-1.26)) when compared to whites, Medicaid when compared to Medicare (IRR 1.37 (95% CI 1.34-1.41)). Higher Elixhauser index corresponded to longer LOS (IRR 1.14 (CI 1-14-1.14)). In terms of hospital factors, Urban teaching hospital was associated with longer LOS when compared to rural hospital (IRR 1.18 (95% CI 1.16-1.19)), Northeast compared to West region hospital areas (IRR 1.3 (95% CI 1.27-1.33)). Decreasing LOS was seen over the course of last 20 years. Conclusion: Admission for ischemic stroke tended to result in longer length of stay among non-Parkinson’s patients. Patient characteristics are a greater source of variability in length of stay than Parkinson’s disease status.

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Medication Management Performance in Parkinson’s Disease: Examination of Process Errors

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab004 ◽

2021 ◽

Author(s):

Catherine A Sumida ◽

Francesca V Lopez ◽

Emily J Van Etten ◽

Nicole Whiteley ◽

Raeanne C Moore ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Negative Binomial ◽

Memory Performance ◽

Medication Management ◽

Negative Binomial Regression ◽

Healthy Adults ◽

Neuropsychological Battery ◽

Management Ability ◽

Normal Cognition

Abstract Objective Individuals with Parkinson’s disease (PD) are at risk for increased medication mismanagement, which can lead to worse clinical outcomes. However, the nature of the errors (i.e., undertaking or overtaking medications) contributing to mismanagement and their relationship to cognition in PD is unknown. Therefore, this study sought to examine errors committed on the Medication Management Ability Assessment (MMAA) between PD participants with normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) relative to healthy adults (HA). Method HA (n = 74), PD-NC (n = 102), and PD-MCI (n = 45) participants were administered the MMAA to assess undertaking, overtaking, and overall errors as well as overall performance (total score). Additionally, participants were administered a comprehensive neuropsychological battery from which cognitive composites of Attention, Learning, Memory, Language, Visuospatial, and Executive Functioning were derived. Results Separate negative binomial regression analyses indicated the PD-MCI group performed significantly worse overall on the MMAA (total score) and committed more undertaking and overall errors relative to HA and PD-NC. In the PD-MCI group, poorer MMAA performance was associated with worse delayed memory performance, whereas cognitive performance was not related to MMAA in HA or PC-NC. Conclusion Compared to PD and healthy adults with normal cognition, PD-MCI patients exhibited greater difficulty with medication management, particularly with undertaking medications. Poorer medication management in PD-MCI was associated with worse delayed recall. Thus, PD-MCI patients experiencing memory problems may require additional assistance with their medications. Findings have clinical relevance suggesting that objective measures of medication errors may assist clinicians in identifying PD patients needing adherence strategies.

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Sex Differences in Brain and Cognition in de novo Parkinson's Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.791532 ◽

2022 ◽

Vol 13 ◽

Author(s):

Javier Oltra ◽

Carme Uribe ◽

Anna Campabadal ◽

Anna Inguanzo ◽

Gemma C. Monté-Rubio ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sex Differences ◽

Brain Atrophy ◽

De Novo ◽

Behavior Disorder ◽

Hippocampal Volume ◽

Healthy Controls ◽

Sleep Behavior ◽

Verbal Recall

Background and Objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients.Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males: 78 females) and 69 healthy controls (40 males: 29 females) were obtained from the PPMI dataset.Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function.Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.

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