The prognostic utility of CSF neurogranin in predicting future cognitive decline in the Alzheimer's disease continuum: A systematic review and meta-analysis with narrative synthesis

Core cerebrospinal fluid (CSF) biomarkers (A beta 42, T-tau, P-tau) were included as supporting diagnostic criteria for Alzheimer's Disease (AD), but they lack the power to predict AD progression. On the other hand, a new biomarker CSF Neurogranin (Ng) has been shown to predict cognitive decline. This systematic review aims to synthesise the prognostic utility of CSF Ng in predicting cognitive decline in the AD continuum. Seven databases were searched systematically from inception to 30 September 2020. Participants were 55 years or older, who had baseline and at least one follow-up cognitive assessments. Risk of bias was assessed using the Quality in Prognosis Studies tool. Meta-analysis was conducted by pooling standardised beta coefficients and adjusted hazard ratios. Thirteen studies were included and high-quality evidence suggests that CSF Ng predicts Mini-Mental State Examination (MMSE) decline in A beta+ mild cognitive impairment (MCI). Moderate quality evidence showed that CSF Ng could predict the decline of memory and executive function in MCI. Narrative synthesis found that CSF Ng/ A beta 42 was also likely to predict cognitive decline. More studies are required to validate the use of CSF Ng as an AD prognostic marker and its application in future development of drug treatment and diagnosis.