Plasma MIA, CRP, and Albumin Predict Cognitive Decline in Parkinson's Disease

Abstract

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 declinedefined by change in MoCA or development of incident mild cognitive impairment (MCI) or dementiain 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.

Serum albumin and white matter hyperintensities

“…Similarly, in elderly patients with epilepsy, those with MMSE-determined cognitive impairment relative to those without impairment showed lower albumin [ 100 ]. Other clinical populations also demonstrate a relation between cognitive impairment and low serum albumin [e.g., Parkinson’s disease [ 50 ], post-stroke patients with type 2 diabetes mellitus [ 101 ], older adults with cognitive impairment [ 102 , 103 ], elderly dialysis patients [ 104 – 106 ]]. Indeed, HIV mono-infected [ 107 ] and HIV + HCV co-infected [ 108 ] individuals with cognitive impairment, including disturbed visual memory in HIV + HCV-coinfection [ 109 ], have low serum albumin.…”

“…Relationships between low serum albumin and cognitive impairment have been described in a variety of clinical populations [e.g., 1,511 patients with heart failure, albumin < 3.5g/dL, multiple sites, Italy [ 45 ]; 1,284 adults ≥55 years, albumin = 4.4±0.3g/dL, Amsterdam, Netherlands [ 46 ]; 2,550 Chinese adults ≥55 years, albumin < 4.0g/dL, Singapore [ 47 ]; 433 hip fracture patients ≥65 years, albumin = 3.51±0.47g/dL, Israel [ 48 ]; 1,752 adults ≥65 years, albumin = 3.9±0.4g/dL, multiple sites, England [ 49 ]; 191 patients with Parkinson’s Disease, albumin levels unspecified, Pennsylvania, U.S. [ 50 ]; 274 patients with acute heart failure, albumin = 3.4±0.4g/dL, Osaka, Japan [ 51 ]]. Of note, serum albumin can be low, but not below clinical cutoffs to affect cognitive performance [ 47 – 49 ].…”

An interpretable multiparametric radiomics model of basal ganglia to predict dementia conversion in Parkinson’s disease

“…Cognitive impairment is commonly observed in patients with PD even at the early stages and can severely affect the quality of life and function, which necessitates identification of predictors of future cognitive decline in PD 12 . Several predictors have been proposed as markers for ongoing cognitive decline in PD, including age, genetic variation in APOE and MAPT, gait disturbance, motor assessments, non-motor symptoms, electroencephalogram analysis results, cognitive profiles, as well as several plasma biomarkers (e.g., α-synuclein/Aβ40, MIA, CRP, and albumin) 13 – 16 . In addition, several neuroimaging studies have shown that structural and functional integrity measured by MRI data can be a useful marker for early dementia conversion in patients with PD 8 , 17 – 20 .…”

Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression

“…The potential influence of CRP polymorphisms has been examined in non-psychiatric and psychiatric conditions. A host of non-psychiatric conditions have been examined and reported; they include conditions ranging from cardiovascular disease, cancer, stroke, sepsis, adiposity, COVID 2019, and others ( Geng et al, 2016 ; Shangwei et al, 2017 ; Delongui et al, 2017 ; Shen et al, 2022 ; Tängdén et al, 2022 ; Huang et al, 2013 ). In regard to psychiatric disorders, there are a relatively limited number of studies, although the common outcome is confirmation of an association between CRP blood levels and SNPs, further differentiated between homozygotic vs heterozygotic alleles.…”