- Email: [email protected]
IC-P1-031: 11C PiB and structural magnetic resonance imaging in Mild Cognitive Impairment
Alzheimer’s Imaging Consortium IC-P1: Poster Presentations Background: The PET tracer 11C labeled Pittsburgh Compound-B (11C-PIB) specifically binds to amyloid- (A) and has been reported to be useful to differentiate Alzheimer’s disease (AD) from frontotemporal dementia (FTD). Serial neuropathological investigation of our Gerontology Hospital autopsy cases has revealed the A accumulation is observed as a continuous profile among normal aging and even in non-AD degenerative disorders such as FTD. The purpose of this study is to evaluate the role of A accumulation in FTD patients. Methods: We studied fifteen patients of FTD and fifteen patients with AD meeting the diagnostic criteria and six subjects as healthy controls. All the subjects underwent PET study with 11C-PIB and 18F-FDG. All the patients were followed up clinically at least one year. Three FTD patients had two 11C-PIB scans with one-year interval, and nine FTD patients had multiple 18F-FDG PET scans to monitor the disease progression. The 11C-PIB accumulation was evaluated with the summing image from 40 to 60 min after the injection with the cerebellar cortex was used as a reference region. The images were evaluated by visual inspection, measurements with regions of interest, and statistical analysis with statistical parametric mapping (SPM). Results: Three FTD patients had 11C-PIB accumulation as high as the level of AD group. Those patients may be the contamination of AD as the limitation of clinical diagnostic criteria. In the rest of 12 FTD patients, the average of 11C-PIB accumulation was not significantly higher than that of healthy controls. However, four of them had mild 11C-PIB accumulation, and three of them underwent follow up 11C-PIB scan revealing increasing 11C-PIB accumulation in one-year follow up. The FTD patients with increasing 11C-PIB accumulation have a trend to demonstrate relatively rapid progression of the clinical symptoms in comparison with the patients with negative 11C-PIB accumulation. Conclusions: Mild increase in 11C-PIB accumulation was observed in about a quarter of FTD patients who showed relatively rapid progression of the symptoms. Besides normal aging, A burden may have some pathological role in FTD. Further prospective study and pathological correlation study are required. IC-P1-031
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seven (Fig 2), and the most common discordance pattern was negative PiB with hippocampal atrophy. Conclusions: Most PiB positive aMCI subjects also have hippocampal atrophy and we suspect that this “ADlike” imaging profile indicates that with sufficient follow up all of these subjects will progress to AD. In contrast, we suspect that both the PiB negative aMCI subjects with atrophic hippocampi and the naMCI subjects with atrophic hippocampi have prodromal dementias other than AD, and with sufficient follow up will progress to non-AD dementias. However, this is an un proven hypothesis and longitudinal clinical follow up, preferably to autopsy, is required for confirmation.
11
C PiB AND STRUCTURAL MAGNETIC RESONANCE IMAGING IN MILD COGNITIVE IMPAIRMENT
Clifford R. Jack, Jr., Val J. Lowe, Matthew L. Senjem, Stephen D. Weigand, Maria M. Shiung, Bradley J. Kemp, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Mayo Clinic and Foundation, Rochester, MN, USA. Contact e-mail: [email protected] Background: To date most cross modality comparisons with 11C Pittsburgh Compound B (PiB) have been with FDG PET. Our objective was to compare MRI and 11C PiB findings cross sectionally in subjects with Mild Cognitive Impairment (MCI). We included both amnestic MCI (aMCI, n⫽17) and non-amnestic MCI (naMCI, n⫽5). Subjects who were cognitively normal (CN, n⫽20) and subjects with probable Alzheimer’s disease (AD, n⫽8) were included for reference purposes. Methods: All subjects were imaged with both 11C PiB and MRI in close temporal proximity. A global cortical PiB retention summary measure was derived from six cortical ROIs and normalized by forming a ratio with cerebellar 11C PiB retention. A cut off value of 1.5 of this ratio was used to separate subjects into those labeled “PiB positive” vs “PiB negative”. Hippocampal volumes were measured from MRI and corrected for age, gender and head size to form co-variate adjusted Z scores labeled “W scores”. Results: All AD subjects were PiB positive and had atrophic hippocampi (Fig 1). While the majority of CN subjects were PiB negative and had no hippocampal atrophy, 6/20 CN were PiB positive. All 5 naMCI subjects were PiB negative; 3/5 had no hippocampal atrophy. Nine of 17 aMCI subjects were PiB positive and most (all but 2) also had atrophic hippocampi. Eight of 17 aMCI subjects were PiB negative and 5 of these also had atrophic hippocampi. Of the 17 aMCI subjects in the study, PiB and MRI were discordant in
IC-P1-032
THE PARIETAL AND PREFRONTAL LOBE ARE CHARACTERIZED BY DISSIMILAR AGERELATED ATROPHY PATTERNS
Heidi I. L. Jacobs1,2, Martin P. J. Van Boxtel1,2, Ed H. B. M. Gronenschild1,2, Floortje Smeets1,2, Saartje Burgmans1,2, Harry B. M. Uylings1,3, Frans R. J. Verhey1,2, Jelle Jolles1,2. 1University Maastricht, Maastricht, Netherlands; 2European Graduate School of Neuroscience EURON, Maastricht, Netherlands; 3Department of Anatomy and Neuroscience, VU University Medical Centre, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: To examine whether there is a differential effect in retrograde aging between parietal and frontal areas of older individuals and whether this pattern is more prominent in persons with cognitive decline compared to healthy individuals. In an earlier study, we found an age-related atrophy pattern in the parietal lobe, with the late-developing association areas being more affected than the somatosensory area. Methods: The somatosensory cortex was taken as a proxy for the area where the least amount of age-related atrophy is expected. This area was compared to the association areas of the prefrontal lobe. The inferior prefrontal area develops before the dorsolateral prefrontal area and thus, an inverted aging pattern was expected. Furthermore a comparable degree of age-related atrophy is expected to be found in the
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seven (Fig 2), and the most common discordance pattern was negative PiB with hippocampal atrophy. Conclusions: Most PiB positive aMCI subjects also have hippocampal atrophy and we suspect that this “ADlike” imaging profile indicates that with sufficient follow up all of these subjects will progress to AD. In contrast, we suspect that both the PiB negative aMCI subjects with atrophic hippocampi and the naMCI subjects with atrophic hippocampi have prodromal dementias other than AD, and with sufficient follow up will progress to non-AD dementias. However, this is an un proven hypothesis and longitudinal clinical follow up, preferably to autopsy, is required for confirmation.
11
C PiB AND STRUCTURAL MAGNETIC RESONANCE IMAGING IN MILD COGNITIVE IMPAIRMENT
Clifford R. Jack, Jr., Val J. Lowe, Matthew L. Senjem, Stephen D. Weigand, Maria M. Shiung, Bradley J. Kemp, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Mayo Clinic and Foundation, Rochester, MN, USA. Contact e-mail: [email protected] Background: To date most cross modality comparisons with 11C Pittsburgh Compound B (PiB) have been with FDG PET. Our objective was to compare MRI and 11C PiB findings cross sectionally in subjects with Mild Cognitive Impairment (MCI). We included both amnestic MCI (aMCI, n⫽17) and non-amnestic MCI (naMCI, n⫽5). Subjects who were cognitively normal (CN, n⫽20) and subjects with probable Alzheimer’s disease (AD, n⫽8) were included for reference purposes. Methods: All subjects were imaged with both 11C PiB and MRI in close temporal proximity. A global cortical PiB retention summary measure was derived from six cortical ROIs and normalized by forming a ratio with cerebellar 11C PiB retention. A cut off value of 1.5 of this ratio was used to separate subjects into those labeled “PiB positive” vs “PiB negative”. Hippocampal volumes were measured from MRI and corrected for age, gender and head size to form co-variate adjusted Z scores labeled “W scores”. Results: All AD subjects were PiB positive and had atrophic hippocampi (Fig 1). While the majority of CN subjects were PiB negative and had no hippocampal atrophy, 6/20 CN were PiB positive. All 5 naMCI subjects were PiB negative; 3/5 had no hippocampal atrophy. Nine of 17 aMCI subjects were PiB positive and most (all but 2) also had atrophic hippocampi. Eight of 17 aMCI subjects were PiB negative and 5 of these also had atrophic hippocampi. Of the 17 aMCI subjects in the study, PiB and MRI were discordant in
IC-P1-032
THE PARIETAL AND PREFRONTAL LOBE ARE CHARACTERIZED BY DISSIMILAR AGERELATED ATROPHY PATTERNS
Heidi I. L. Jacobs1,2, Martin P. J. Van Boxtel1,2, Ed H. B. M. Gronenschild1,2, Floortje Smeets1,2, Saartje Burgmans1,2, Harry B. M. Uylings1,3, Frans R. J. Verhey1,2, Jelle Jolles1,2. 1University Maastricht, Maastricht, Netherlands; 2European Graduate School of Neuroscience EURON, Maastricht, Netherlands; 3Department of Anatomy and Neuroscience, VU University Medical Centre, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: To examine whether there is a differential effect in retrograde aging between parietal and frontal areas of older individuals and whether this pattern is more prominent in persons with cognitive decline compared to healthy individuals. In an earlier study, we found an age-related atrophy pattern in the parietal lobe, with the late-developing association areas being more affected than the somatosensory area. Methods: The somatosensory cortex was taken as a proxy for the area where the least amount of age-related atrophy is expected. This area was compared to the association areas of the prefrontal lobe. The inferior prefrontal area develops before the dorsolateral prefrontal area and thus, an inverted aging pattern was expected. Furthermore a comparable degree of age-related atrophy is expected to be found in the