CSF and PET biomarkers for noradrenergic dysfunction in neurodegenerative disease: A systematic review and meta‐analysis. (31st December 2021)

• Record Type: Journal Article
• Authors: Lancini, Elisa; Bartl, Franziska; Haag, Lena; Rühling, Maren; Ashton, Nicholas J; Zetterberg, Henrik; Düzel, Emrah; Hämmerer, Dorothea; Betts, Matthew
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055942
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Alterations to the noradrenergic system may occur in the early stages of Alzheimer's disease (AD) and Parkinson's disease (PD) and could contribute to clinical symptoms. The aim of this study was to conduct a meta‐analysis of noradrenergic differences in AD and PD assessed using cerebrospinal fluid (CSF) and positron emission tomography (PET) measures Method: CSF noradrenaline (NA) and its metabolite 3‐Methoxy‐4‐hydroxyphenylglycol (MHPG) as well as NA transporter availability (PET MeNER) levels in controls, AD and PD patients were pooled across studies. Differences between controls and patients were calculated with Hedge's g and combined using a random‐effects model meta‐analysis. A random‐effect meta‐regression was conducted using the volume of the CSF samples, the sample sizes, the years post diagnosis, the severity of the diseases as covariates using laboratory analysis technique as a between‐study factor. Result: Twenty‐seven studies met the inclusion criteria. Seven studies with extreme effect sizes influencing between‐study heterogeneity were identified as outliers and subsequently removed from further analyses. In PD patients, significant reductions in CSF NA (n= 132, g= ‐0.26, p=0.01) and MHPG (n=257, g = ‐0.27, p<0.01), in addition to reduced PET MeNER binding in the hypothalamus (n=29, g = ‐0.87, p<0.05), were observed compared with control subjects (n=166 for NA, n=227 for MHPG respectively). In AD patients, no significant difference in CSF NA levels (n=194, g= ‐0.06, p= 0.78) and only a trend for increased MHPG levels (n=208, g= 0.24, p= 0.07) were observed compared with controls (n=196 for NA, n=218 for MHPG respectively), see Figure 1 . The number of articles addressing PET MeNER in AD was not sufficient to conduct a meta‐analysis. The hypothesized explanatory variables, namely the volume of CSF samples, the sample size, the years post diagnosis and the severity of the disease, were not significant (p>0.05) in any of the investigated groups. Conclusion: Our results indicate that noradrenergic dysfunction in neurodegenerative diseases can be detected using CSF or PET measures and may be more pronounced in PD compared to AD. Further studies using longitudinal CSF and PET measures are required to elucidate the relationship between noradrenergic dysfunction and the progression of neurodegenerative diseases.