Association of MRI-measured cerebral ventricular volume with APOE E4 genotype, cerebrospinal fluid biomarker (amyloid-beta 42 and Tau) and neuropsychological measures in Alzheimer's disease: A Systematic Review

Rationale and ObjectivesAlthough neuroimaging studies suggest that the cerebral ventricle is independently associated with APOE {varepsilon}4, cerebrospinal fluid (CSF) biomarkers, and neuropsychological scores in aging and Alzheimers disease (AD), there is no formal synthesis of these findings. We summarized the association of ventricular changes with APOE {varepsilon}4, CSF biomarkers, and neuropsychological measures. Materials and MethodsThe Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline was used. PubMed, Scopus, Ovid, Cochrane, and grey literature were searched, and assessment of eligible articles was conducted using the Newcastle-Ottawa Scale. Results24 studies met the inclusion criteria. Progressive ventricular volume is increased in AD patients at an average volume of 4.4 - 4.7 cm3/ year compared to average volumes of 2.7 - 2.9 cm3/ year and 1.1 - 1.4 cm3/year for patients with MCI and healthy controls (HCs) respectively. The ventricular volume is estimated to increase by 1.7 cm3/year for progression from MCI to AD. APOE {varepsilon}4 is an independent risk factor for ventricular enlargement in aging and dementia, with AD patients most affected. The combination of CSF A{beta}42 with ventricular volume compared to tau is more robust, for tracking the progression of the AD continuum. Further, the combination of ventricular volume with mini-mental state examination (MMSE) scores is the most robust for differentiating AD and MCI from HCs and tracking the progression of the disease. ConclusionThe combination of ventricular volume with APOE {varepsilon}4, CSF A{beta}42, and MMSE scores independently may be potentially useful biomarkers for differentiating and tracking the progression of AD.