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

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.

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

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.

scholarly journals Predicting the onset of freezing of gait in de novo Parkinson’s disease

2021 ◽  
Author(s):  
Fengting Wang ◽  
Yixin Pan ◽  
Miao Zhang ◽  
Kejia Hu
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Freezing Of Gait ◽  
Poor Quality ◽  
Csf Biomarkers ◽  
Genetic Characteristics ◽  
Progression Markers ◽  
Independent Risk Factors

AbstractFreezing of gait (FoG) is a debilitating symptom of Parkinson’s disease (PD) related to higher risks of falls and poor quality of life. In this study, we predicted the onset of FoG in PD patients using a battery of risk factors from patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) cohort. The endpoint was the presence of FoG, which was assessed every year during the five-year follow-up visit. Overall, 212 PD patients were included in analysis. Seventy patients (33.0%) developed FoG during the visit (pre-FoG group). Age, bradykinesia, TD/PIGD classification, fatigue, cognitive impairment, impaired autonomic functions and sleep disorder were found to be significantly different in patients from pre-FoG and non-FoG groups at baseline. The logistic regression model showed that motor factors such as TD/PIGD classification (OR = 2.67, 95% CI = 1.41-5.09), MDS-UPDRS part III score (OR = 1.05, 95% CI = 1.01-1.09) were associated with FoG occurrence. Several indicators representing non-motor symptoms such as SDMT total score (OR = 0.95, 95% CI = 0.91-0.98), HVLT immediate/Total recall (OR = 0.91, 95% CI = 0.86-0.97), MOCA (OR = 0.87, 95% CI = 0.76-0.99), Epworth Sleepiness Scale (OR = 1.13, 95% CI = 1.03-1.24), fatigue(OR = 1.98, 95% CI = 1.32-3.06), SCOPA-AUT gastrointestinal score (OR = 1.27, 95% CI = 1.09-1.49) and SCOPA-AUT urinary score (OR = 1.18, 95% CI = 1.06-1.32) were found to have the predictive value. PD patients that developed FoG showed a significant reduction of DAT uptake in the striatum. However, no difference at baseline was observed in genetic characteristics and CSF biomarkers between the two patient sets. Our model indicated that TD/PIGD classification, MDS-UPDRS total score, and Symbol Digit Modalities score were independent risk factors for the onset of FoG in PD patients. In conclusion, the combination of motor and non-motor features including the akinetic subtype and poor cognitive functions should be considered in identifying PD patients with high risks of FoG onset.

Cognitive and cortical thinning patterns of subjective cognitive decline in patients with and without Parkinson's disease

2014 ◽  
Vol 20 (9) ◽  
pp. 999-1003 ◽  
Author(s):  
Jin Yong Hong ◽  
Hyuk Jin Yun ◽  
Mun Kyung Sunwoo ◽  
Jee Hyun Ham ◽  
Jong-Min Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Cortical Thinning

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

2017 ◽  
Vol 89 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Byoung Seok Ye ◽  
Seun Jeon ◽  
Sohoon Yoon ◽  
Seong Woo Kang ◽  
KyoungWon Baik ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Atrophy ◽  
Negative Binomial ◽  
De Novo ◽  
Neuropsychiatric Symptoms ◽  
Brain Mri ◽  
Negative Binomial Regression ◽  
Cortical Thinning ◽  
Positron Emission

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.

scholarly journals White matter hyperintensities are linked to future cognitive decline in de novo Parkinson's disease patients

2018 ◽  
Vol 20 ◽  
pp. 892-900 ◽  
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

Serum Neurofilament Dynamics Predicts Cognitive Progression in de novo Parkinson’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Ling-Zhi Ma ◽  
Can Zhang ◽  
Han Wang ◽  
Ya-Hui Ma ◽  
Xue-Ning Shen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Cox Regression ◽  
De Novo ◽  
Rate Of Change ◽  
Neurofilament Light ◽  
Baseline Serum ◽  
Axon Damage ◽  
High Concentrations

Background: Neurofilament light (NfL) can reflect the extent of neuron/axon damage, thus providing an opportunity to examine the severity and progression of the diseases with such damage. Objective: Whether serum NfL can be used as an indicator to monitor the cognitive progress of de novo Parkinson’s disease (PD) remains unclear. Methods: In this research, 144 healthy controls and 301 de novo PD patients from Parkinson’s Progression Markers Initiative (PPMI) were recruited. Linear mixed effects models were used to examine the associations of baseline/longitudinal serum NfL with cognitive decline. Cox regression was used to detect cognitive progression in PD participants. Results: We found PD patients had higher serum NfL than controls at baseline (p = 0.031), and NfL increase was faster in PD group (p < 0.001). Both baseline serum NfL and its rate of change predicted measurable cognitive decline in early PD (MoCA, β= –0.014, p < 0.001; β= –0.002, p < 0.001, respectively). Additionally, we observed that NfL levels were also able to predict progression in different diagnostic groups and Amyloid- PD and Amyloid+PD groups. After an average follow-up of 6.37±1.84 years, the baseline NfL of the third tertile of high concentrations was associated with a future high risk of PD dementia (adjusted HR 6.33, 95% CI 2.62–15.29, p < 0.001). Conclusion: In conclusion, our results indicated that the serum NfL concentration could function as an easily accessible biomarker to monitor the severity and progression of cognitive decline in PD.

scholarly journals Latent Cognitive Phenotypes in De Novo Parkinson’s Disease: A Person-Centered Approach

2017 ◽  
Vol 23 (7) ◽  
pp. 551-563 ◽  
Author(s):  
Denise R. LaBelle ◽  
Ryan R. Walsh ◽  
Sarah J. Banks
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Latent Class ◽  
De Novo ◽  
Demographic Data ◽  
Functional Independence ◽  
Cognitive Change ◽  
Cognitive Profiles ◽  
Consistent Performance

AbstractObjectives: Cognitive impairment is an important aspect of Parkinson’s disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Methods: Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson’s Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Results: Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor (“Weak-Overall”), average (“Typical-Overall”), and strong (“Strong-Overall”) cognition. The remaining classes demonstrated unique patterns of cognition, characterized by “Strong-Memory,” “Weak-Visuospatial,” and “Amnestic” profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer’s disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Conclusions: Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551–563)

scholarly journals In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease

Brain ◽  
2017 ◽  
Vol 141 (1) ◽  
pp. 165-176 ◽  
Author(s):  
Nicola J Ray ◽  
Steven Bradburn ◽  
Christopher Murgatroyd ◽  
Umar Toseeb ◽  
Pablo Mir ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Basal Forebrain ◽  
De Novo ◽  
Cholinergic Basal Forebrain

scholarly journals Iron Accumulation Is Not Homogenous among Patients with Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Khashayar Dashtipour ◽  
Manju Liu ◽  
Camellia Kani ◽  
Pejman Dalaie ◽  
Andre Obenaus ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Iron Content ◽  
De Novo ◽  
Brain Regions ◽  
Iron Accumulation ◽  
Loma Linda University ◽  
Neurology Clinic ◽  
The Brain ◽  
Possible Cause

Background. Iron is considered to lead to neurodegeneration and has been hypothesized as a possible cause of Parkinson’s disease (PD). Susceptibility-weighted imaging (SWI) is a powerful tool to measure phase related iron content of brain.Methods. Twelve de novo patients with PD were recruited from the Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve age- and sex-matched non-PD subjects were recruited from neurology clinic as controls. Using SWI, the phase related iron content was estimated from different brain regions of interest (ROIs).Results. There was a trend between increasing age and iron accumulation in the globus pallidus and putamen in all subjects. Iron accumulation was not significant in different ROIs in PD patients compared to controls after adjustment for age. Our data revealed heterogeneity of phase values in different brain ROIs among all subjects with an exaggerated trend at SN in PD patients.Conclusions. Our data suggest a nonhomogeneous pattern of iron accumulation in different brain regions among PD patients. Further studies are needed to explore whether this may correlate to the progression of PD. To our knowledge, this is the first study demonstrating the heterogeneity of iron accumulation in the brain, among patients with PD.

Potential Sex-Specific Effects of Apolipoprotein E ɛ4 on Cognitive Decline in Early Parkinson’s Disease

2020 ◽  
pp. 1-9
Author(s):  
Ryul Kim ◽  
Sangmin Park ◽  
Dallah Yoo ◽  
Young Ju Suh ◽  
Jin-Sun Jun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Apolipoprotein E ◽  
De Novo ◽  
Sensitivity Analyses ◽  
Specific Effects ◽  
E4 Allele ◽  
Generalized Linear Mixed Effects

Background/Objective: To compare the longitudinal trajectories of cognition according to the presence of the apolipoprotein E (APOE) ɛ4 allele in male and female Parkinson’s disease (PD) patients. Methods: This study included a total of 361 patients with recently diagnosed de novo PD (mean age [standard deviation], 61.4 [9.8] years). The patients were classified into the following groups: APOE ɛ4 + /M (n = 65), APOE ɛ4-/M (n = 173), APOE ɛ4 + /F (n = 25), and APOE ɛ4-/F (n = 98). Cognitive decline was assessed annually over 5 years of follow-up using the Montreal Cognitive Assessment (MoCA). To assess the sex-specific impacts of the APOE ɛ4 status on cognitive decline, we used generalized linear mixed effects (GLME) models separately for men, women, and the two sexes combined. Results: In the sex-stratified GLME models adjusted for covariates, the interaction results showed that the males with APOE ɛ4 had a steeper rate of cognitive decline than those without APOE ɛ4. In contrast, there was no significant interaction between APOE ɛ4 and time on longitudinal MoCA performance in the females. The main effect of APOE ɛ4 on the change in the MoCA score was not significant for either men or women. When the data from both men and women were used, the APOE ɛ4 + /M group exhibited a steeper rate of cognitive decline than did the APOE ɛ4 + /F and APOE ɛ4-/F groups. These results were consistent with those of sensitivity analyses. Conclusion: Sex may be considered when APOE ɛ4-related vulnerability to early cognitive decline is evaluated in PD patients.

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