Browsing by Author "Groot, Colin"

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    Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns
    (Wiley, 2024) Crane, Paul K.; Groot, Colin; Ossenkoppele, Rik; Mukherjee, Shubhabrata; Choi, Seo-Eun; Lee, Michael; Scollard, Phoebe; Gibbons, Laura E.; Sanders, R. Elizabeth; Trittschuh, Emily; Saykin, Andrew J.; Mez, Jesse; Nakano, Connie; Mac Donald, Christine; Sohi, Harkirat; Alzheimer’s Disease Neuroimaging Initiative; Risacher, Shannon; Medicine, School of Medicine
    Introduction: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. Methods: We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. Results: There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10-10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. Discussion: MRI findings differ across cognitively defined AD subgroups.
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    Correction: Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217
    (BMC, 2022-06-13) Groot, Colin; Cicognola, Claudia; Bali, Divya; Triana‑Baltzer, Gallen; Dage, Jeffrey L.; Pontecorvo, Michael J.; Kolb, Hartmuth C.; Ossenkoppele, Rik; Janelidze, Shorena; Hansson, Oskar; Neurology, School of Medicine
    Erratum for: Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217. Groot C, Cicognola C, Bali D, Triana-Baltzer G, Dage JL, Pontecorvo MJ, Kolb HC, Ossenkoppele R, Janelidze S, Hansson O. Alzheimers Res Ther. 2022 May 14;14(1):67. doi: 10.1186/s13195-022-01005-8. PMID: 35568889
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    Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217
    (BMC, 2022-05-14) Groot, Colin; Cicognola, Claudia; Bali, Divya; Triana‑Baltzer, Gallen; Dage, Jeffrey L.; Pontecorvo, Michael J.; Kolb, Hartmuth C.; Osssenkoppele, Rik; Janelidze, Shorena; Hansson, Oskar; Neurology, School of Medicine
    Background: Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer's disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217Lilly, within two independent cohorts. METHODS: The study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/-) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays. Results: Both assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+Janssen AUC = 0.88 vs p-tau217Lilly AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+Janssen rho = -0.39 vs p-tau217Lilly rho = -0.35), and annual change in MMSE scores (plasma p-tau217+Janssenr = -0.45 vs p-tau217Lillyr = -0.41). Correlations between the two plasma measures were rho = 0.69, p < 0.001 in cohort 1 and rho = 0.70, p < 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+Janssen and plasma p-tau217Lilly in both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI). Conclusions: Taken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+Janssen assay, similar to the p-tau217Lilly assay.
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    Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer's disease subgroups
    (Elsevier, 2021) Groot, Colin; Grothe, Michel J.; Mukherjee, Shubhabrata; Jelistratova, Irina; Jansen, Iris; van Loenhoud, Anna Catharina; Risacher, Shannon L.; Saykin, Andrew J.; Mac Donald, Christine L.; Mez, Jesse; Trittschuh, Emily H.; Gryglewski, Gregor; Lanzenberger, Rupert; Pijnenburg, Yolande A.L.; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M.; Crane, Paul K.; Ossenkoppele, Rik; Radiology and Imaging Sciences, School of Medicine
    The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups of amyloid-β positive individuals clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 ± 5). All participants underwent neuropsychological assessment with tests covering memory, executive-functioning, language and visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment compared to the intra-individual average across domains, which yielded the following subgroups in our sample; AD-Memory (n = 41), AD-Executive (n = 117), AD-Language (n = 33), AD-Visuospatial (n = 171). We performed voxel-wise contrasts of GM volumes derived from 3Tesla structural MRI between subgroups and controls (n = 127, age 58 ± 9, 42% male, MMSE 29 ± 1), and observed that differences in regional GM volumes compared to controls closely matched the respective cognitive profiles. Specifically, we detected lower medial temporal lobe GM volumes in AD-Memory, lower fronto-parietal GM volumes in AD-Executive, asymmetric GM volumes in the temporal lobe (left < right) in AD-Language, and lower GM volumes in posterior areas in AD-Visuospatial. In order to examine possible biological drivers of these differences in regional GM volumes, we correlated subgroup-specific regional GM volumes to brain-wide gene expression profiles based on a stereotactic characterization of the transcriptional architecture of the human brain as provided by the Allen human brain atlas. Gene-set enrichment analyses revealed that variations in regional expression of genes involved in processes like mitochondrial respiration and metabolism of proteins were associated with patterns of regional GM volume across multiple subgroups. Other gene expression vs GM volume-associations were only detected in particular subgroups, e.g., genes involved in the cell cycle for AD-Memory, specific sets of genes related to protein metabolism in AD-Language, and genes associated with modification of gene expression in AD-Visuospatial. We conclude that cognitively-defined AD subgroups show neurobiological differences, and distinct biological pathways may be involved in the emergence of these differences.
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    Differential trajectories of hypometabolism across cognitively-defined Alzheimer’s disease subgroups
    (Elsevier, 2021) Groot, Colin; Risacher, Shannon L.; Chen, J.Q. Alida; Dicks, Ellen; Saykin, Andrew J.; MacDonald, Christine L.; Mez, Jesse; Trittschuh, Emily H.; Mukherjee, Shubhabrata; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M.; Ossenkoppele, Rik; Crane, Paul K.; Radiology and Imaging Sciences, School of Medicine
    Disentangling biologically distinct subgroups of Alzheimer's disease (AD) may facilitate a deeper understanding of the neurobiology underlying clinical heterogeneity. We employed longitudinal [18F]FDG-PET standardized uptake value ratios (SUVRs) to map hypometabolism across cognitively-defined AD subgroups. Participants were 384 amyloid-positive individuals with an AD dementia diagnosis from ADNI who had a total of 1028 FDG-scans (mean time between first and last scan: 1.6 ± 1.8 years). These participants were categorized into subgroups on the basis of substantial impairment at time of dementia diagnosis in a specific cognitive domain relative to the average across domains. This approach resulted in groups of AD-Memory (n = 135), AD-Executive (n = 8), AD-Language (n = 22), AD-Visuospatial (n = 44), AD-Multiple Domains (n = 15) and AD-No Domains (for whom no domain showed substantial relative impairment; n = 160). Voxelwise contrasts against controls revealed that all AD-subgroups showed progressive hypometabolism compared to controls across temporoparietal regions at time of AD diagnosis. Voxelwise and regions-of-interest (ROI)-based linear mixed model analyses revealed there were also subgroup-specific hypometabolism patterns and trajectories. The AD-Memory group had more pronounced hypometabolism compared to all other groups in the medial temporal lobe and posterior cingulate, and faster decline in metabolism in the medial temporal lobe compared to AD-Visuospatial. The AD-Language group had pronounced lateral temporal hypometabolism compared to all other groups, and the pattern of metabolism was also more asymmetrical (left < right) than all other groups. The AD-Visuospatial group had faster decline in metabolism in parietal regions compared to all other groups, as well as faster decline in the precuneus compared to AD-Memory and AD-No Domains. Taken together, in addition to a common pattern, cognitively-defined subgroups of people with AD dementia show subgroup-specific hypometabolism patterns, as well as differences in trajectories of metabolism over time. These findings provide support to the notion that cognitively-defined subgroups are biologically distinct.