Objective: Using a multi-cohort, discovery-replication-validation design, we sought new plasma biomarkers that predict which individuals with Parkinson's disease (PD) will experience cognitive decline.
Methods: In 108 discovery cohort PD individuals and 83 replication cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associated with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which patients with PD showed fast (> = 1 point drop/year on Montreal Cognitive Assessment [MoCA]) versus slow (< 1 point drop/year on MoCA) cognitive decline in the discovery cohort, testing it in the replication cohort. We developed alternate assays for the top 3 proteins and confirmed their ability to predict cognitive decline - defined by change in MoCA or development of incident mild cognitive impairment (MCI) or dementia - in a validation cohort of 118 individuals with PD. We investigated the top plasma biomarker for causal influence by Mendelian randomization (MR).
Results: A model with only 3 proteins (melanoma inhibitory activity protein [MIA], C-reactive protein [CRP], and albumin) separated fast versus slow cognitive decline subgroups with an area under the curve (AUC) of 0.80 in the validation cohort. The individuals with PD in the validation cohort in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA single nucleotide polymorphism (SNP) rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA's causal influence.
Conclusions: An easily obtained plasma-based predictor identifies individuals with PD at risk for cognitive decline. MIA may participate causally in development of cognitive decline. ANN NEUROL 2022;92:255-269.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329215 | PMC |
| http://dx.doi.org/10.1002/ana.26410 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Depressive Symptoms and Amyloid Pathology.
JAMA Psychiatry
January 2025
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.
View Article and Find Full Text PDFAMPA Receptors in Synaptic Plasticity, Memory Function, and Brain Diseases.
Cell Mol Neurobiol
January 2025
Laboratory of Neurobiology, Centro de Investigaciones Medico Sanitarias (CIMES), University of Malaga, Calle Marqués de Beccaria, 3, Campus Teatinos s/n, 29010, Malaga, Spain.
Tetrameric AMPA-type ionotropic glutamate receptors are primary transducers of fast excitatory synaptic transmission in the central nervous system, and their properties and abundance at the synaptic surface are crucial determinants of synaptic efficacy in neuronal communication across the brain. The induction of long-term potentiation (LTP) leads to the insertion of GluA1-containing AMPA receptors at the synaptic surface, whereas during long-term depression (LTD), these receptors are internalized into the cytoplasm of the spine. Disruptions in the trafficking of AMPA receptors to and from the synaptic surface attenuate both forms of synaptic plasticity.
View Article and Find Full Text PDFmiR-32533 Reduces Cognitive Impairment and Amyloid-β Overload by Targeting CREB5-Mediated Signaling Pathways in Alzheimer's Disease.
Adv Sci (Weinh)
January 2025
Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, P. R. China.
MicroRNAs (miRNAs) are associated with amyloid-β (Aβ) dysmetabolism, a pivotal factor in the pathogenesis of Alzheimer's disease (AD). This study unveiled a novel miRNA, microRNA-32533 (miR-32533), featuring a distinctive base sequence identified through RNA sequencing of the APPswe/PSEN1dE9 (APP/PS1) mouse brain. Its role and underlying mechanisms were subsequently explored.
View Article and Find Full Text PDFHypotensive Episodes Identified on 24-Hour Ambulatory Blood Pressure and Impaired Cognitive Function: Insights From the SPRINT Study.
Hypertension
January 2025
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (W.Z., D.H., M.A.M., Y.M.).
Background: Hypotensive episodes detected by 24-hour ambulatory blood pressure (BP) monitoring capture daily cumulative hypotensive stress and could be clinically relevant to cognitive impairment, but this relationship remains unclear.
Methods: We included participants from the Systolic Blood Pressure Intervention Trial (receiving intensive or standard BP treatment) who had 24-hour ambulatory BP monitoring measured near the 27-month visit and subsequent biannual cognitive assessments. We evaluated the associations of hypotensive episodes (defined as systolic BP drops of ≥20 mm Hg between 2 consecutive measurements that reached <100 mm Hg) and hypotensive duration (cumulative time of systolic BP <100 mm Hg) with subsequent cognitive function using adjusted linear mixed models.
Coexistence of Anti-GAD and Anti-GABAAR Antibodies in an Autoimmune Encephalitis Patient: A Case Report.
Int Med Case Rep J
January 2025
Department of Neurology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, People's Republic of China.
Background: Coexistence of autoimmune encephalitis (AE) with multiple autoantibodies is of particular concern because overlying antibodies may cause variation of clinical manifestations. Coexistence of anti-glutamic acid decarboxylase (GAD) and anti-Gamma-aminobutyric acid-α-receptor (GABAAR) antibodies in AE was rare.
Case Presentation: A 44-year-old female patient presented to our hospital due to cognitive decline for 4 years, seizures, slowed speech and depression for 2 months.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!