%0 Journal Article %J J Alzheimers Dis %D 2018 %T A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER). %A Niemantsverdriet, Ellis %A Ribbens, Annemie %A Bastin, Christine %A Benoit, Florence %A Bergmans, Bruno %A Bier, Jean-Christophe %A Bladt, Roxanne %A Claes, Lene %A De Deyn, Peter Paul %A Deryck, Olivier %A Hanseeuw, Bernard %A Ivanoiu, Adrian %A Lemper, Jean-Claude %A Mormont, Eric %A Picard, Gaëtane %A Salmon, Eric %A Segers, Kurt %A Sieben, Anne %A Smeets, Dirk %A Struyfs, Hanne %A Thiery, Evert %A Tournoy, Jos %A Triau, Eric %A Vanbinst, Anne-Marie %A Versijpt, Jan %A Bjerke, Maria %A Engelborghs, Sebastiaan %X

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.

%B J Alzheimers Dis %V 63 %P 1509-1522 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29782314?dopt=Abstract %R 10.3233/JAD-171140 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Patients with Amyloid-Negative Mild Cognitive Impairment have Cortical Hypometabolism but the Hippocampus is Preserved. %A Hanseeuw, Bernard %A Dricot, Laurence %A Lhommel, Renaud %A Quenon, Lisa %A Ivanoiu, Adrian %X

BACKGROUND: Patients with mild cognitive impairment (MCI) are at risk for Alzheimer's dementia but the presence of amyloid (Aβ) strongly increases this risk. In clinical settings, when Aβ status is not available, different neurodegenerative markers are used to characterize MCI. The accuracy of these markers to discriminate between Aβ-and Aβ+ MCI is not yet determined.

OBJECTIVE: To compare different markers of neurodegeneration in Aβ-and Aβ+ MCI, with an Aβ-elderly control (EC) group.

METHODS: Patients with MCI (n = 39) and EC (n = 28) underwent MRI, 18F-FDG PET, and Aβ PET (18F-flutemetamol). We compared FDG and MRI biomarker values in cortical and hippocampal regions of interest, and using voxel-wise surface maps. We computed ROC curves discriminating between the three groups for each biomarker.

RESULTS: All biomarker values were reduced in Aβ+ MCI compared to EC (p < 0.001). Aβ-MCI had low cortical metabolism (p = 0.002), but hippocampal volume, cortical thickness, and hippocampal metabolism were not significantly different between Aβ-MCI and EC (p > 0.40). Cortical metabolism best discriminated between MCI and EC (AUC = 0.92/0.86, Aβ+/Aβ-) while hippocampal volume best discriminated between Aβ-MCI and Aβ+ MCI (AUC = 0.79).

CONCLUSIONS: Cortical hypometabolism was observed in both Aβ-MCI and Aβ+ MCI whereas hippocampal atrophy was mostly found in Aβ+ MCI. For MCI patients without available Aβ information, hippocampal atrophy is thus more informative about Aβ status than cortical hypometabolism.

%B J Alzheimers Dis %V 53 %P 651-60 %8 2016 May 23 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27232217?dopt=Abstract %R 10.3233/JAD-160204 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Targretin Improves Cognitive and Biological Markers in a Patient with Alzheimer's Disease. %A Pierrot, Nathalie %A Lhommel, Renaud %A Quenon, Lisa %A Hanseeuw, Bernard %A Dricot, Laurence %A Sindic, Christian %A Maloteaux, Jean-Marie %A Octavea, Jean-Noël %A Ivanoiu, Adrian %K Aged %K Alzheimer Disease %K Amyloidogenic Proteins %K Biomarkers %K Cognition Disorders %K Humans %K Male %K Mental Recall %K Neuropsychological Tests %K Receptors, Retinoic Acid %K tau Proteins %K Tetrahydronaphthalenes %X

We present the effects of Targretin® (bexarotene) on cognition and biomarkers in a patient with mild Alzheimer's disease (AD). Targretin® is a Retinoic X Receptor (RXR) agonist shown to improve synaptic and cognitive functions in animal models of AD by increasing neuronal cholesterol efflux. After 6 months of treatment with Targretin® 300 mg/day, memory improved by about 40% and the tau protein in the cerebrospinal fluid decreased by about 20% . No significant side effects were noticed. This observation in a single patient indicates that Targretin® may improve memory performance and biological markers at an early stage of AD.

%B J Alzheimers Dis %V 49 %P 271-6 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26444777?dopt=Abstract %R 10.3233/JAD-150405