Cognitive Performance and Cerebrospinal Fluid Biomarkers of Neurodegeneration: A Study of Patients with Bipolar Disorder and Healthy Controls

Background Cross-sectional studies have found impaired cognitive functioning in patients with bipolar disorder, but long-term longitudinal studies are scarce. Aims The aims of this study were to examine the 6-year longitudinal course of cognitive functioning in patients with bipolar disorder and healthy controls. Subsets of patients were examined to investigate possible differences in cognitive trajectories. Method Patients with bipolar I disorder (n = 44) or bipolar II disorder (n = 28) and healthy controls (n = 59) were tested with a comprehensive cognitive test battery at baseline and retested after 6 years. We conducted repeated measures ANCOVAs with group as a between-subject factor and tested the significance of group and time interaction. Results By and large, the change in cognitive functioning between baseline and follow-up did not differ significantly between participants with bipolar disorder and healthy controls. Comparing subsets of patients, for example those with bipolar I and II disorder and those with and without manic episodes during follow-up, did not reveal subgroups more vulnerable to cognitive decline. Conclusions Cognitive performance remained stable in patients with bipolar disorder over a 6-year period and evolved similarly to healthy controls. These findings argue against the notion of a general progressive decline in cognitive functioning in bipolar disorder.

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Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.667179 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kaat Hebbrecht ◽

Katrien Skorobogatov ◽

Erik J. Giltay ◽

Violette Coppens ◽

Livia De Picker ◽

...

Keyword(s):

Bipolar Disorder ◽

Cerebrospinal Fluid ◽

Methodological Quality ◽

Meta Analysis ◽

Random Effect ◽

Healthy Controls ◽

Significant Difference ◽

Subgroup Analyses ◽

Tryptophan Catabolites

ObjectiveTryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.MethodsA systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.ResultsTwenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.ConclusionThe TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.

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Cerebrospinal Fluid Biomarkers Distinguish Postmortem-Confirmed Alzheimer's Disease from Other Dementias and Healthy Controls in the OPTIMA Cohort

Journal of Alzheimer s Disease ◽

10.3233/jad-141725 ◽

2015 ◽

Vol 44 (2) ◽

pp. 525-539 ◽

Cited By ~ 34

Author(s):

Jeffrey L. Seeburger ◽

Daniel J. Holder ◽

Marc Combrinck ◽

Catharine Joachim ◽

Omar Laterza ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Healthy Controls ◽

Cerebrospinal Fluid Biomarkers

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Brevican and Neurocan Peptides as Potential Cerebrospinal Fluid Biomarkers for Differentiation Between Vascular Dementia and Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201039 ◽

2020 ◽

pp. 1-13

Author(s):

Karolina Minta ◽

Gunnar Brinkmalm ◽

Erik Portelius ◽

Per Johansson ◽

Johan Svensson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vascular Dementia ◽

Extracellular Enzymes ◽

Control Group ◽

Healthy Controls ◽

Clear Trend ◽

Cerebrospinal Fluid Biomarkers

Background: Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF). Objective: The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer’s disease (AD) and vascular dementia (VaD) compared with controls. Methods: The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry. Results: In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls. Conclusion: Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.

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