A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER)

Abstract

Background: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD).

Objective: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression.

Methods: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available.

Results: The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment.

Conclusion: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

Keywords: Alzheimer’s disease; MSmetrix; biomarkers; magnetic resonance image; volumetry.

Fig.1

WB, GM, and CGM volumes across the different clinical diagnosis. Scatterplots of WB (A), GM (B), and CGM (C) volumes in mL per clinical diagnostic category with their corresponding mean±SD. Significant differences were reported between clinical diagnoses, p = 0.001* or p < 0.05 (a-d). Volumes were significantly different between a clinical diagnostic group and cognitively healthy controls (a), to SCD (b), to MCI (c), or to AD dementia patients (d). WB was significantly different between all diagnostic groups. GM was significantly different between all diagnostic groups, except between controls and SCD. The CGM was significantly different between controls and SCD versus MCI and AD dementia. AD, Alzheimer’s disease; CGM, cortical grey matter; GM, grey matter; MCI, mild cognitive impairment; SCD, subjective cognitive decline; SD, standard deviation; WB, whole brain.

Fig.2

WB, GM, and CGM volumes across slow and fast decliners in the total population based on MMSE. Scatterplots of WB (A), GM (B), and CGM (C) volumes in mL at baseline with their corresponding mean±SD. The MMSE slopes were calculated based on the difference in MMSE scores and were divided by the follow-up time. Subjects were categorized as slow decliners in case the MMSE slope was smaller than three, and if the slope was equal or larger than three a subject was categorized as a fast decliner. Significant differences were found for all volumes showed. CGM, cortical grey matter; GM, grey matter; MMSE, Mini-Mental State examination; SD, standard deviation; WB, whole brain.