scholarly journals Baseline concentration of misfolded α‐synuclein aggregates in cerebrospinal fluid predicts risk of cognitive decline in Parkinson's disease

2018 ◽  
Vol 45 (4) ◽  
pp. 398-409 ◽  
Author(s):  
H. Ning ◽  
Q. Wu ◽  
D. Han ◽  
T. Yao ◽  
J. Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Baseline Concentration

Decoupling of Global Brain Activity and Cerebrospinal Fluid Flow in Parkinson's Disease Cognitive Decline

2021 ◽  
Author(s):  
Feng Han ◽  
Gregory L. Brown ◽  
Yalin Zhu ◽  
Aaron E. Belkin‐Rosen ◽  
Mechelle M. Lewis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Cognitive Decline ◽  
Brain Activity ◽  
Cerebrospinal Fluid Flow ◽  
Global Brain

Ratios of proteins in cerebrospinal fluid in Parkinson's disease cognitive decline: prospective study

2018 ◽  
Vol 33 (11) ◽  
pp. 1809-1813 ◽  
Author(s):  
Manuel Delgado-Alvarado ◽  
Rosalía Dacosta-Aguayo ◽  
Irene Navalpotro-Gómez ◽  
Belén Gago ◽  
Ana Gorostidi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Prospective Study ◽  
Cognitive Decline

scholarly journals Cerebrospinal fluid N-224 tau helps discriminate Alzheimer’s disease from subjective cognitive decline and other dementias

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Claudia Cicognola ◽  
Oskar Hansson ◽  
Philip Scheltens ◽  
Hlin Kvartsberg ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Study Cohort ◽  
Not Otherwise Specified ◽  
T Tau

Abstract Background Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer’s disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls. Methods Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (Aβ42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay. Results N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson’s disease (PD, p < 0.0001), Parkinson’s disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R2 = 0.318, β = 0.564, p ≤ 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824). Conclusions N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.

scholarly journals Biomarkers of neurodegeneration and glial activation validated in Alzheimer’s disease assessed in longitudinal cerebrospinal fluid samples of Parkinson’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0257372
Author(s):  
Michael Bartl ◽  
Mohammed Dakna ◽  
Douglas Galasko ◽  
Samantha J. Hutten ◽  
Tatiana Foroud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Neurofilament Light Chain ◽  
Significant Difference

Aim Several pathophysiological processes are involved in Parkinson’s disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated in Alzheimer’s Disease, in a PD cohort. Methods Longitudinal cerebrospinal fluid (CSF) samples from PPMI (252 PD, 115 healthy controls, HC) were analyzed at six timepoints (baseline, 6, 12, 24, 36, and 48 months follow-up) using Elecsys® electrochemiluminescence immunoassays to quantify neurofilament light chain (NfL), soluble TREM2 receptor (sTREM2), chitinase-3-like protein 1 (YKL40), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), S100, and total α-synuclein (αSyn). Results αSyn was significantly lower in PD (mean 103 pg/ml vs. HC: 127 pg/ml, p<0.01; area under the curve [AUC]: 0.64), while all other biomarkers were not significantly different (AUC NfL: 0.49, sTREM2: 0.54, YKL40: 0.57, GFAP: 0.55, IL-6: 0.53, S100: 0.54, p>0.05) and none showed a significant difference longitudinally. We found significantly higher levels of all these markers between PD patients who developed cognitive decline during follow-up, except for αSyn and IL-6. Conclusion Except for αSyn, the additional biomarkers did not differentiate PD and HC, and none showed longitudinal differences, but most markers predict cognitive decline in PD during follow-up.

scholarly journals Modifiable comorbidities associated with cognitive decline in Parkinson's Disease

2020 ◽  
Author(s):  
Emily Forbes ◽  
Thomas F. Tropea ◽  
Sneha Mantri ◽  
Sharon X. Xie ◽  
James F. Morley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline

scholarly journals Which Neuropsychological Tests? Predicting Cognitive Decline and Dementia in Parkinson’s Disease in the ICICLE-PD Cohort

2021 ◽  
pp. 1-12
Author(s):  
Rachael A. Lawson ◽  
Caroline H. Williams-Gray ◽  
Marta Camacho ◽  
Gordon W. Duncan ◽  
Tien K. Khoo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Verbal Fluency ◽  
Neuropsychological Tests ◽  
Visual Memory ◽  
Attention And Memory ◽  
Memory And Attention ◽  
Global Cognition

Background: Cognitive impairment is common in Parkinson’s disease (PD), with 80% cumulatively developing dementia (PDD). Objective: We sought to identify tests that are sensitive to change over time above normal ageing so as to refine the neuropsychological tests predictive of PDD. Methods: Participants with newly diagnosed PD (n = 211) and age-matched controls (n = 99) completed a range of clinical and neuropsychological tests as part of the ICICLE-PD study at 18-month intervals over 72 months. Impairments on tests were determined using control means (<1-2SD) and median scores. Mild cognitive impairment (PD-MCI) was classified using 1-2SD below normative values. Linear mixed effects modelling assessed cognitive decline, while Cox regression identified baseline predictors of PDD. Results: At 72 months, 46 (cumulative probability 33.9%) participants had developed PDD; these participants declined at a faster rate in tests of global cognition, verbal fluency, memory and attention (p <  0.05) compared to those who remained dementia-free. Impaired baseline global cognition, visual memory and attention using median cut-offs were the best predictors of early PDD (area under the curve [AUC] = 0.88, p <  0.001) compared to control-generated cut-offs (AUC = 0.76–0.84, p <  0.001) and PD-MCI (AUC] = 0.64–0.81, p <  0.001). Impaired global cognition and semantic fluency were the most useful brief tests employable in a clinical setting (AUC = 0.79, p <  0.001). Conclusion: Verbal fluency, attention and memory were sensitive to change in early PDD and may be suitable tests to measure therapeutic response in future interventions. Impaired global cognition, attention and visual memory were the most accurate predictors for developing a PDD. Future studies could consider adopting these tests for patient clinical trial stratification.

scholarly journals The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson’s Disease: Explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline

2021 ◽  
Vol 11 (2) ◽  
pp. 455-474
Author(s):  
Per Borghammer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Explanatory Power ◽  
Anatomical Location ◽  
Asymmetric Distribution ◽  
Motor Asymmetry ◽  
Parasympathetic Innervation ◽  
Considerable Body ◽  
Dopaminergic Degeneration

A new model of Parkinson’s disease (PD) pathogenesis is proposed, the α-Synuclein Origin site and Connectome (SOC) model, incorporating two aspects of α-synuclein pathobiology that impact the disease course for each patient: the anatomical location of the initial α-synuclein inclusion, and α-synuclein propagation dependent on the ipsilateral connections that dominate connectivity of the human brain. In some patients, initial α-synuclein pathology occurs within the CNS, leading to a brain-first subtype of PD. In others, pathology begins in the peripheral autonomic nervous system, leading to a body-first subtype. In brain-first cases, it is proposed that the first pathology appears unilaterally, often in the amygdala. If α-synuclein propagation depends on connection strength, a unilateral focus of pathology will disseminate more to the ipsilateral hemisphere. Thus, α-synuclein spreads mainly to ipsilateral structures including the substantia nigra. The asymmetric distribution of pathology leads to asymmetric dopaminergic degeneration and motor asymmetry. In body-first cases, the α-synuclein pathology ascends via the vagus to both the left and right dorsal motor nuclei of the vagus owing to the overlapping parasympathetic innervation of the gut. Consequently, the initial α-synuclein pathology inside the CNS is more symmetric, which promotes more symmetric propagation in the brainstem, leading to more symmetric dopaminergic degeneration and less motor asymmetry. At diagnosis, body-first patients already have a larger, more symmetric burden of α-synuclein pathology, which in turn promotes faster disease progression and accelerated cognitive decline. The SOC model is supported by a considerable body of existing evidence and may have improved explanatory power.

Analyses of Visuospatial and Visuoperceptual Errors as Predictors of Dementia in Parkinson’s Disease Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

2020 ◽  
pp. 1-11
Author(s):  
Iván Galtier ◽  
Antonieta Nieto ◽  
María Mata ◽  
Jesús N. Lorenzo ◽  
José Barroso
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Poor Performance ◽  
Subjective Cognitive Decline ◽  
Independent Risk Factors

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.

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