11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment.

By Clifford R. Jack Jr., V. Lowe, Matthew L. Senjem, S. Weigand, B. Kemp, M. Shiung, D. Knopman, Brad Boeve, William E. Klunk, Chester A. Mathis and 1 more. Brain : a journal of neurology, 2008

936 citations recorded by the source corpus.

To date, most diagnostic imaging comparisons between amyloid labelling ligands and other imaging modalities have been between the use of amyloid labelling ligand (11)C Pittsburgh Compound B (PiB) and FDG-PET. Our objectives were to compare cognitive performance and diagnostic group-wise discrimination between cognitively normal, amnestic mild cognitive impairment (MCI) and Alzheimer's disease subjects with MRI-based measures of hippocampal volume and PiB retention, and secondly to evaluate the topographic distribution of PiB retention and grey matter loss using 3D voxel-wise methods. Twenty cognitively normal, 17 amnestic MCI and 8 probable Alzheimer's disease subjects were imaged with both MRI and PiB. PiB retention was quantified as the ratio of uptake in cortical to cerebellar regions of interest (ROIs) 40-60 min post-injection. A global cortical PiB retention summary measure was derived from six cortical ROIs. Statistical parametric mapping (SPM) and voxel-based morphometry (VBM) were used to evaluate PiB retention and grey matter loss on a 3D voxel-wise basis. Alzheimer's disease subjects had high global cortical PiB retention and low hippocampal volume; most cognitively normal subjects had low PiB retention and high hippocampal volume; and on average amnestic MCI subjects were intermediate on both PiB and hippocampal volume. A target-to-cerebellar ratio of 1.5 was used to designate subjects with high or low PiB cortical retention. All Alzheimer's disease subjects fell above this ratio, as did 6 out of 20 cognitively normal subjects and 9 out of 17 MCI subjects, indicating bi-modal PiB retention in the latter two groups. Interestingly, we found no consistent differences in learning and memory performance between high versus low PiB cognitively normal or amnestic MCI subjects. The SPM/VBM voxel-wise comparisons of Alzheimer's disease versus cognitively normal subjects provided complementary information in that clear and meaningful similarities and differences in topographical distribution of amyloid deposition and grey matter loss were shown. The frontal lobes had high PiB retention with little grey matter loss, anteromedial temporal areas had low PiB retention with significant grey matter loss, whereas lateral temporoparietal association cortex displayed both significant PiB retention and grey matter loss. A voxel-wise SPM conjunction analysis revealed that subjects with high PiB retention shared a common PiB retention topographical pattern regardless of clinical category, and this matched that of amyloid plaque distribution from autopsy studies of Alzheimer's disease. Both global cortical PiB retention and hippocampal volumes demonstrated significant correlation in the expected direction with cognitive testing performance; however, correlations were stronger with MRI than PiB. Pair-wise inter-group diagnostic separation was significant for all group-wise pairs for both PiB and hippocampal volume with the exception of the comparison of cognitively normal versus amnestic MCI, which was not significant for PiB. PiB and MRI provided complementary information such that clinical diagnostic classification using both methods was superior to using either in isolation.

Subfields: Cognitive Neuroscience, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/0a3a207fde1aecf73134e3382c94d1f268edd93a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

In Physiology

In Psychiatry and Mental health

Citations in the corpus

Neural Correlates of Alzheimer's Disease and Mild Cognitive Impairment: A Systematic and Quantitative Meta-Analysis involving 1,351 Patients (2009, neutral): “…might be caused by regional amyloid deposits as indicated by histopathological and imaging studies (Braak and Braak, 1991b; Chételat et al., 2008; Jack et al., 2008; Kemppainen et al., 2007), and by disconnection from the hippocampus through disruption of the cingulum bundle (so called…”
Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease (2009, neutral): “…evidenced by data in the current study as well as other independent studies that have consistently found signiﬁcant PIB retention in up to 1/3 of cognitively normal elderly subjects (Mintun et al ., 2006; Aizenstein et al ., 2008; Gomperts et al ., 2008; Jack et al ., 2008b; Mormino et al ., 2008).”
Mild cognitive impairment: ten years later. (2009, background): “Several recent studies have suggested that, depending on the stage in the clinical spectrum, certain neuroimaging and biomarker measures or their combinations may be quite informative.(48) As shown in Figure 4, it is possible that a deposition of amyloid is the initial event, characterized by a low ”
Introduction to Revised Criteria for the Diagnosis of Alzheimer’s Disease: National Institute on Aging and the Alzheimer Association Workgroups (2011, background): “Thus, the set of recommendations presented in this article only refer to other disorders because they relate to differential diagnosis of AD.”
The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease (2011, neutral): “These measures appear to provide evidence about the stage or severity of disease that may not be provided by Aβ biomarkers [21].”
Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives (2010, neutral): “These amyloid-PET scans have provided information regarding the Aβ plaque burden that is independent from structural changes in brain anatom”
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease (2011, background): “Biomarkers of brain amyloid-beta (Ab) protein deposition are low CSF Ab42 and positive PET amyloid imaging [22,23].”
Predicting regional neurodegeneration from the healthy brain functional connectome. (2012, background): “Interestingly, numerous frontal regions exhibit striking resistance to AD-related neurodegeneration despite having high fibrillar amyloid-beta deposition (Jack et al., 2008) and, as shown here, short functional paths to the angular gyrus in some instances.”