Abstract
The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (Aβ)1-42, ratios of Aβ42/40 and Aβ42/38, soluble amyloid precursor protein α and β, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers. In patients, the CSF biomarkers explained a significant proportion of the variance (15–36%, p=.002 - <.0005) in all cognitive domains independently of age, medication, disease status, and bipolar subtype I or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain changes, i.e., P-tau and Aβ1-42, did not contribute significantly. In healthy controls, CSF biomarkers did not explain the variance in cognitive performance. Selected CSF biomarkers of neurodegenerative processes accounted for cognitive performance in persons with bipolar disorder, but not for healthy controls. Specifically, the ratios of Aβ42/40 and Aβ42/38 were consistently associated with altered cognitive performance.
Highlights
The hallmark of bipolar disorder is recurrent episodes of depression and mania or hypomania [1]
We found decreased concentrations of the soluble forms amyloid precursor protein (APP)—sAPPα and sAPPβ - and higher ratios of amyloid β (Aβ) 42/40 and Aβ42/38 in persons with bipolar disorder compared with healthy controls [16]
To investigate if the associations between cerebrospinal fluid (CSF) biomarkers and cognitive performance were specific to bipolar disorder, this study included healthy controls (Table 2)
Summary
The hallmark of bipolar disorder is recurrent episodes of depression and mania or hypomania [1]. The worldwide prevalence of the main subtypes of bipolar disorder, type I and II, is estimated to about 1–3% [2]. Meta-analyses suggest that attention/speed, memory, and executive functions are impaired in euthymic bipolar disorder [5, 6]. An independent individual patient data meta-analysis provided further evidence of significant cognitive impairment in bipolar disorder, albeit less substantial than previous reports suggested [7]. Another meta-analysis found that differences between bipolar type I and II are negligible with the exception of memory and semantic fluency [8]. Whereas there is some evidence of cognitive deterioration during the course of illness [7, 9], most cognitive functions appear to remain persistently impaired over time [10]
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