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.

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline

“…There was no indication of an overall brain volume difference between groups. This pattern of results contrasts with some previous studies that compared individuals with MCI who converted to dementia and individuals who did not convert to dementia (eg, ). Nevertheless, as expected, hippocampus volume was smaller in individuals who underestimated their decline relative to individuals who overestimated their decline.…”

“…This study compared memory performance, brain volume, and CSF There was no indication of an overall brain volume difference between groups. This pattern of results contrasts with some previous studies that compared individuals with MCI who converted to dementia and individuals who did not convert to dementia (eg, 28 Thus, the current analyses are consistent with the proposed model of progression of AD, according to which the accumulation of amyloidbeta and tau, together with hypometabolism, lead to cognitive decline. 29 Note, though, that there are conflicting observations regarding the correlation between Aß 1-42 levels and deterioration in cognitive functions, 30 and similar inconclusive evidence for longitudinal changes in p-tau both in individuals with MCI and in individuals with AD.…”

Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease

“… Fan et al (2018) [ 77 ] Memory clinic consultation T1 MRI and DTI Cross-sectional NC: n = 34 (67.8 ± 7.4) SCD: n = 43 (66.1 ± 7.0) aMCI: n = 44 (73.9 ± 8.0) SCD showed cortical atrophy and decreased mean FA. Niemantsverdriet et al (2018) [ 127 ] Criteria by SCD-I T1 MRI Cross-sectional NC: n = 93 (67.3 ± 8.5) SCD: n = 102 (68.6 ± 9.8) MCI: n = 379 (74.6 ± 8.0) AD: n = 313 (77.5 ± 8.0) Baseline whole brain, gray matter, cortical gray matter and increased CSF volumes predicted cognitive impairment Verfaillie et al (2018) [ 94 , 99 , 128 ] Referred by general practitioners or medical specialists T1 MRI Cross-sectional SCD: n = 233 (52.8 ± 9.2) SCD with faster subsequent memory loss was associated with thinner cortex of the frontal and occipital cortices. Verfaillie et al (2018) [ 94 , 99 , 128 ] Memory clinic consultation T1 MRI Cross-sectional SCD: n = 231 (63.0 ± 9.2) SCD with lower network size was associated with steeper decline in language.…”

Comparison of Vendor-Provided Volumetry Software and NeuroQuant Using 3D T1-Weighted Images in Subjects with Cognitive Impairment: How Large is the Inter-Method Discrepancy?

“…Currently, several commercially available clinical volumetry software are being studied (5)(6)(7)(8). Diagnostic accuracy of these software has been extensively studied (4,(9)(10)(11). In patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), the diagnostic accuracy of hippocampal volumetry ranges 83-88% (4,(9)(10)(11).…”

“…Diagnostic accuracy of these software has been extensively studied (4,(9)(10)(11). In patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), the diagnostic accuracy of hippocampal volumetry ranges 83-88% (4,(9)(10)(11). However, analytical accuracy parameters such as reliability, reproducibility, and measured bias have been evaluated in only a few studies (9,12).…”