Inflammatory Biomarkers in Newly Diagnosed Patients With Parkinson Disease and Related Neurodegenerative Disorders.

BACKGROUND AND OBJECTIVES: Neuroinflammation contributes to Parkinson disease (PD) pathology, and inflammatory biomarkers may aid in PD diagnosis. Proximity extension assay (PEA) technology is a promising method for multiplex analysis of inflammatory markers. Neuroinflammation also plays a role in related neurodegenerative diseases, such as dementia with Lewy bodies (DLB) and Alzheimer disease (AD). The aim of this work was to assess the value of inflammatory biomarkers in newly diagnosed patients with PD and in patients with DLB and AD. METHODS: Patients from the Norwegian ParkWest and Dementia Study of Western Norway longitudinal cohorts (PD, n = 120; DLB, n = 15; AD, n = 27) and 44 normal controls were included in this study. A PEA inflammation panel of 92 biomarkers was measured in the CSF. Disease-associated biomarkers were identified using elastic net (EN) analysis. We assessed the discriminatory power of disease-associated biomarkers using receiver operating characteristic (ROC) curve analysis and estimated the optimism-adjusted area under the curve (AUC) using the bootstrapping method. RESULTS: EN analysis identified 9 PEA inflammatory biomarkers (ADA, CCL23, CD5, CD8A, CDCP1, FGF-19, IL-18R1, IL-6, and MCP-2) associated with PD. Seven of the 9 biomarkers were included in a diagnostic panel, which was able to discriminate between those with PD and controls (optimism-adjusted AUC 0.82). Our 7-biomarker PD panel was also able to distinguish PD from DLB and from AD. In addition, 4 inflammatory biomarkers were associated with AD and included in a panel, which could distinguish those with AD from controls (optimism-adjusted AUC 0.87). Our 4-biomarker AD panel was also able to distinguish AD from DLB and from PD. DISCUSSION: In our exploratory study, we identified a 7-biomarker panel for PD and a 4-biomarker panel for AD. Our findings indicate potential inflammation-related biomarker candidates that could contribute toward PD-specific and AD-specific diagnostic panels, which should be further explored in other larger cohorts.

Serum Potassium Is Associated with Cognitive Decline in Patients with Lewy Body Dementia.

BACKGROUND: Epidemiological studies link serum potassium (K+) to cognitive performance, but whether cognitive prognosis in dementia is related to K+ levels is unknown. OBJECTIVE: To determine if K+ levels predict cognitive prognosis in dementia and if this varies according to diagnosis or neuropathological findings. METHODS: This longitudinal cohort study recruited 183 patients with mild Alzheimer's disease or Lewy body dementia (LBD). Serum K+ and eGFR were measured at baseline and medications which could affect K+ registered. The Mini-Mental State Examination (MMSE) was measured annually over 5 years, and mortality registered. Association between K+ and √(30 -MMSE) was estimated overall, and according to diagnosis (joint model). Associations between MMSE-decline and K+ were assessed in two subgroups with neuropathological examination (linear regression) or repeated measurements of K+ over 3 years (mixed model). RESULTS: Serum K+ at baseline was associated with more errors on MMSE over time (Estimate 0.18, p = 0.003), more so in LBD (p = 0.048). The overall association and LBD interaction were only significant in the 122 patients not using K+ relevant medication. Repeated K+ measures indicated that the association with MMSE errors over time was due to a between-person effect (p < 0.05, n = 57). The association between the annual MMSE decline was stronger in patients with autopsy confirmed LBD and more α-synuclein pathology (all: p < 0.05, n = 41). CONCLUSION: Higher serum K+ predicts poorer cognitive prognosis in demented patients not using medications which affect K+, likely a between-person effect seen mainly in LBD.

[Biomarkers in spinal fluid of patients with dementia]. / Biomarkører i spinalvæske ved demens.

BACKGROUND: We wanted to assess whether biomarkers abeta42, tau and p-tau could differentiate between Alzheimer's disease and other dementia illnesses. MATERIAL AND METHODS: Following systematic Pubmed searches, 25 articles which reported sensitivity and specificity for Alzheimer's disease and other dementias were included. RESULTS: Most studies showed significant differences for all three markers between Alzheimer's disease and other dementia illnesses, except abeta42 which did not differ between Alzheimer's disease and dementia with Lewy bodies. Alzheimer's disease was distinguished from vascular dementia with sensitivities and specificities 77 % - 87 % and 62-80 % (abeta42); 79-100 % and 14-100 % (tau); and 78-80 % and 63-96 % (p-tau181). Alzheimer's disease and dementia with Lewy bodies were differentiated by tau and p-tau181 with sensitivities and specificities of 72-94 % and 53-92 %, and of 68-85 % and 61-85 %. Markers separated Alzheimer's disease from frontal lobe dementia with sensitivities and specificities of 37-91 % and 59-92 % (abeta42), 58-88 % and 68-92 % (tau) and 44-91 % and 79-100 % (p-tau181). INTERPRETATION: Methodological weaknesses impede the interpretation. CSF markers are not yet sufficient to differentiate between Alzheimer's disease and other forms of dementia.