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CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease.

ABSTRACT: In early-stage Parkinson's disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1-2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = -0.59), attentional (sβ = -0.32), and executive functioning (sβ = -0.35). Reduced CSF amyloid-β42 levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = -0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.

SUBMITTER: Oosterveld LP

PROVIDER: S-EPMC7697681 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease.

Oosterveld Linda P LP Kuiper Tessa I TI Majbour Nour K NK Verberk Inge M W IMW van Dijk Karin D KD Twisk Jos W R JWR El-Agnaf Omar M OM Teunissen Charlotte E CE Weinstein Henry C HC Klein Martin M Berendse Henk W HW van de Berg Wilma D J WDJ

International journal of molecular sciences 20201112 22

In early-stage Parkinson's disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β<sub>42</sub>, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α- ...[more]

PMID: 33198266

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Project description:ObjectiveThis systematic review, performed in accordance with the PRISMA guidelines, seeks to summarize the interventions that have been developed in order to improve executive functioning and attention in children born prematurely.MethodsThe PICOS framework helped guide the structure and relevant terms selected for the study. Electronic systematic searches of the databases PubMed (NLM), Ovid Medline, Ovid All EBM Reviews, Ovid Embase, and Ovid PsycINFO were completed in March 2022. This review focuses on interventions that target attention and executive functioning in prematurely born children between birth and 12 years old, with outcome measures assessed between 3 and 12 years old, even if the age range in the study can exceed our own parameters. Data extraction included sample characteristics, country of recruitment, type of intervention, description of the intervention group and control group, outcome measures, and overall results. An assessment of the quality of methodology of studies was performed through an adaptation of the Downs and Black checklist for both randomized and nonrandomized studies in healthcare interventions. An assessment of the risk of bias was also presented using the Cochrane risk of bias tool for randomized trials 2.0.ResultsA total of 517 premature children received an intervention at some point between birth and early adolescence. Eleven different interventions were assessed in 17 studies, with rating of the quality of methodology and outcomes ranging from lower quality studies (44% quality rating) to robust studies (96% quality rating) in terms of reporting standards, external and internal validity, and power. Five of those studies focused on interventions administered in the neonatal intensive care unit or shortly postdischarge (e.g., the Mother-Infant Transaction Program and the Newborn Individualized Developmental Care and Assessment Program, documented in two articles each [11%] or the Infant Behavioral Assessment and Intervention Program assessed in one study [about 5%]), while 12 articles reported on interventions administered between the ages of 1.5-12 years old [mostly computerized cognitive training programs such as Cogmed (23%) and BrainGame Brian (17%)]. Of the 17 articles examined, 12 (70%) showed positive short-term outcomes postintervention and 3 (17%) demonstrated positive long-term results with small to large effect sizes (0.23-2.3). Among included studies, 50% showed an overall high risk of bias, 21.4% showed some concerns, and 28.6% were low risk of bias.ConclusionsDue to the heterogeneity of the programs reviewed, the presented findings should be interpreted as descriptive results. A careful and individualized selection from the various available interventions should be made based on the target population (i.e., age at intervention administration and outcome testing) before implementing these program protocols in clinical settings.

Project description:BackgroundCortical atrophy is associated with cognitive decline, but the association is not perfect. We aimed to identify factors explaining the discrepancy between the degree of cortical atrophy and cognitive decline in cognitively unimpaired elderly.MethodsThe discrepancy between atrophy and cognitive decline was measured using the residuals from a linear regression analysis between change in whole brain cortical thickness over time and change in a cognitive composite measure over time in 395 cognitively unimpaired participants from the Swedish BioFINDER study. We tested for bivariate associations of this residual measure with demographic, imaging, and fluid biomarker variables using Pearson correlations and independent-samples t-tests, and for multivariate associations using linear regression models. Mediation analyses were performed to explore possible paths between the included variables.ResultsIn bivariate analyses, older age (r = -0.11, p = 0.029), male sex (t = -3.00, p = 0.003), larger intracranial volume (r = -0.17, p < 0.001), carrying an APOEe4 allele (t = -2.71, p = 0.007), larger white matter lesion volume (r = -0.16, p = 0.002), lower cerebrospinal fluid (CSF) β-amyloid (Aβ) 42/40 ratio (t = -4.05, p < 0.001), and higher CSF levels of phosphorylated tau (p-tau) 181 (r = -0.22, p < 0.001), glial fibrillary acidic protein (GFAP; r = -0.15, p = 0.003), and neurofilament light (NfL; r = -0.34, p < 0.001) were negatively associated with the residual measure, i.e., associated with worse than expected cognitive trajectory given the level of atrophy. In a multivariate analysis, only lower CSF Aβ42/40 ratio and higher CSF NfL levels explained cognition beyond brain atrophy. Mediation analyses showed that associations between the residual measure and APOEe4 allele, CSF Aβ42/40 ratio, and CSF GFAP and p-tau181 levels were mediated by levels of CSF NfL, as were the associations with the residual measure for age, sex, and WML volume.ConclusionsOur results suggest that axonal degeneration and amyloid pathology independently affect the rate of cognitive decline beyond the degree of cortical atrophy. Furthermore, axonal degeneration mediated the negative effects of old age, male sex, and white matter lesions, and in part also amyloid and tau pathology, on cognition over time when accounting for cortical atrophy.

Dataset Information

CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease.

Publications

CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease.

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