Alzheimer's disease related biomarkers in bipolar disorder – A longitudinal one-year case-control study

Knorr, Ulla; Simonsen, Anja Hviid; Jensen, Christer; Zetterberg, Henrik; Blennow, Kaj; Akhøj, Morten; Forman, Julie Lyng; Hasselbalch, Steen Gregers; Kessing, Lars Vedel

doi:10.1016/j.jad.2021.10.074

Cited by 22 publications

(18 citation statements)

References 69 publications

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“…We here present the first-ever study on longitudinal associations between cognition and CSF biomarkers of neurodegeneration in patients with BD and healthy control individuals (HC). We have previously from the same cohorts found that abnormalities of amyloid production/clearance during an acute BD episode and that these abnormalities mimic the pattern seen in AD namely decreasing CSF-Aβ42 suggesting an association with brain amyloidosis (Knorr et al 2022 ).…”

Section: Introductionmentioning

confidence: 63%

Biomarkers for neurodegeneration impact cognitive function: a longitudinal 1-year case–control study of patients with bipolar disorder and healthy control individuals

Knorr,

Simonsen,

Zetterberg

et al. 2024

Int J Bipolar Disord

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Background Abnormalities in cerebrospinal fluid (CSF)-amyloid-beta (Aβ)42, CSF-Aβ40, CSF-Aβ38, CSF-soluble amyloid precursor proteins α and β, CSF-total-tau, CSF-phosphorylated-tau, CSF-neurofilament light protein (NF-L), CSF-neurogranin, plasma-Aβ42, plasma-Aβ40, plasma-total-tau, plasma-NF-L and, serum-S100B during affective episodes may reflect brain changes that could impact cognitive function in patients with bipolar disorder (BD). The study aimed to investigate the association between these biomarkers indicative of Alzheimer’s disease and those reflecting neurodegeneration alongside their impact on cognitive function in patients with BD and healthy control individuals (HC). The primary hypothesis was that GL and VL would increase with increasing levels of CSF-Aβ42 based on data from T0 and T3 in BD and HC jointly. Methods In a prospective, longitudinal case–control study euthymic patients with BD (N = 85) and HC (N = 44) were evaluated with clinical assessment and neuropsychological testing at baseline (T0) and during euthymia after a year (T3). Patients’ affective states were recorded weekly as euthymic, subthreshold level, major depression, or (hypo)mania. If an episode occurred during follow-up, the patient was also assessed in post-episode euthymia. Cognitive performance was measured as a global cognitive score (GL) for four cognitive domains including verbal learning and memory (VL). Results Estimated in a linear mixed model GL increased with 0.001 for each increase of 1 pg/ml of CSF-Aβ42 (97.5%, CI 0.00043–0.0018, adjusted-p = 0.0005) while VL increased by 0.00089 (97.5%, CI 0.00015–0.0018, adjusted-p = 0.045) in BD and HC jointly. The association was weak, however stronger in patients with BD compared to HC. Associations between other biomarkers including CSF-neurogranin, and cognitive domains were overall weak, and none remained significant after adjustment for multiple testing. Limitations Modest sample size. A complete data set regarding both CSF-AB-42 and cognitive test scores was obtained from merely 61 patients with BD and 38 HC individuals. Conclusion CSF-Aβ42 may be associated with cognitive dysfunction in patients with BD and HC individuals. The association appeared to be stronger in BD but with overlapping confidence intervals. Hence it remains uncertain whether the association is a general phenomenon or driven by BD.

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Section: Introductionmentioning

confidence: 63%

Biomarkers for neurodegeneration impact cognitive function: a longitudinal 1-year case–control study of patients with bipolar disorder and healthy control individuals

Knorr,

Simonsen,

Zetterberg

et al. 2024

Int J Bipolar Disord

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“…Two studies (41,42) did not have a healthy control group, so were only included in the additional mixed-model meta-analyses. Seventeen studies analysed blood samples, three used CSF, and Knorr et al’s study (16) investigated both CSF and blood. The majority of the studies (75%) were published after 2020, reflecting the relatively recent availability of Simoa and ELISA technology to measure NfL and GFAP in blood.…”

Section: Resultsmentioning

confidence: 99%

Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis

Kang,

Grewal,

Eratne

et al. 2024

Preprint

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BackgroundNeurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal injury measurable in cerebrospinal fluid (CSF) and blood. Despite their potential as diagnostic tests for neurodegenerative disorders, it is unclear how they behave in mood and anxiety disorders. We conducted a systematic review and meta-analysis to investigate whether NfL and GFAP concentrations were altered in adults with mood and anxiety disorders compared to healthy controls.MethodsThe study was prospectively registered on PROSPERO (CRD42023434617). We followed the PRISMA guidelines, searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase up to the 31/05/2023, and assessed relevant studies and their risk of bias. The primary outcome was the standardised mean difference (SMD) and 95% confidence interval (95% CI) of NfL and GFAP concentrations, which was pooled using a random-effects model adopting the restricted maximum likelihood estimator.ResultsTwenty-one studies met inclusion criteria, comprising of 2327 individuals (695 major depression, 502 bipolar disorder, and 1130 controls). When we compared people with major depression and controls, there was no difference in NfL (SMD = 0.29; 95% CI: -0.10, 0.68) nor GFAP (SMD = 0.47; 95% CI: -0.74, 1.68). In people with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.58; 95% CI: 0.16, 0.99). However, the subgroup analysis including more sensitive assay kits (blood Simoa and CSF ELISA), found no significant difference (SMD = 0.40; 95% CI: -0.04, 0.85). Only one study studied GFAP in bipolar disorder. No studies explored NfL nor GFAP concentrations in anxiety disorders.DiscussionWe found that NfL and GFAP concentrations were not elevated in depression. In bipolar disorder, NfL concentration was elevated, though not in the sensitivity analysis. Our study informs clinicians about how to interpret these emerging biomarkers in determining whether a person’s symptoms are caused by a neurodegenerative or mood disorder.

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“…Overall, heterogeneity and inconsistency in previous studies are supporting the search for new potential targets with a clinical value in BD. Several additional inflammatory factors, such as specific chemokines (MCP-1, fractalkine), glial factors (GFAP, S100B), or lipid-derived mediators such as endocannabinoids, and neurodegeneration-related molecules such as neurofilament light chain, neurogranin and β-amyloid peptide isoforms (Aβ42, Aβ40, Aβ38) and their fragments could be promising biomarkers in patients with BD in relation to prospective clinical outcomes, such as those of neuronal injury, cognitive deficits and risk of dementia [ 93 ]. Recent studies have also evaluated non-coding RNA expression, sexual hormones, oxidative stress (uric acid, bilirubin, albumin) and metabolic biomarkers (metabolic syndrome, overweight/obesity, thyroid and liver function) in predicting BD and suicidality in individuals with bipolar disorder [ 94 , 95 , 96 , 97 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis

et al. 2022

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Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = −0.22, Confidence Interval 95% = −0.38, −0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.

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Alzheimer's disease related biomarkers in bipolar disorder – A longitudinal one-year case-control study

Cited by 22 publications

References 69 publications

Biomarkers for neurodegeneration impact cognitive function: a longitudinal 1-year case–control study of patients with bipolar disorder and healthy control individuals

Biomarkers for neurodegeneration impact cognitive function: a longitudinal 1-year case–control study of patients with bipolar disorder and healthy control individuals

Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis

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