- Email: [email protected]
Alzheimer's disease–related changes in subfields of the hippocampal formation using 7T MRI
P64
Alzheimer’s Imaging Consortium Posters: IC-P
SPECT imaging. As there are no non-radioactive Tc isotopes, Re complexes are often synthesised as surrogates to the corresponding 99m Tc analogues for preliminary assessment. A range of novel Re and 99m Tc complexes have been synthesized. These compounds have been assessed for their ability to bind to amyloid in human brain tissue and for preferential uptake in the APP/PS1 mouse of AD. Results: We have developed synthetic methods to prepare [Tc(CO)3(H 2 O)3]+ from [TcO 4]- under aqueous conditions using kit based formulations. This core has then been coordinated to an organic framework specifially designed to bind to amyloid plaques. We have used the intrinsic fluorescence of these compounds to show that they can bind to Ab in human brain slices from AD subjects (fig). Appraisal of the compounds in the APP/PS1 mice is currently ongoing. Conclusions: SPECT is not as quantitative as PET imaging and therefore we do not envisage a scenario wheret SPECT would replace PET imaging. SPECT would supplement PET imaging by acting as a prescreen for the general population to identify individuals at risk of developing AD. This diagnosis this could then be confirmed by PET imaging. We have developed new amyloid binding that have the potential to be effective SPECT imaging agents.
IC-P-116
ALZHEIMER’S DISEASE–RELATED CHANGES IN SUBFIELDS OF THE HIPPOCAMPAL FORMATION USING 7T MRI
Laura Wisse, Geert Jan Biessels, Sophie Heringa, H. Kuijf, H. Koek, Peter Luijten, Mirjam Geerlings, University Medical Center Utrecht, Utrecht, the Netherlands. Background: Post-mortem studies indicate that subfields of the hippocampal formation are differentially affected by normal aging and Alzheimer’s Disease (AD). Recent studies on 3-4Tesla MRI confirm these observations, but mostly assessed the subfields only in the body of the hippocampus or assessed only three subfields. We developed and validated a protocol using isotropic voxels (0.70 mm 3) at 7T MRI to delineate subfields of the hippocampal formation along its full length. In this pilot study using this protocol, we examined whether subfield volumes differ between patients with Mild Cognitive Impairment (MCI)/AD and older persons with normal cognition. Methods: 17 patients (59% women) with MCI (n ¼ 10) or AD (n ¼ 7) were recruited at the UMC Utrecht and 17 elders (65% women) with normal cognition were recruited through GPs in the region. Subjects were scanned with a T2 sequence on a 7T MRI whole body scanner (Philips Healthcare). One rater (LEMW) manually outlined the Entorhinal Cortex (ERC), subiculum (SUB), Cornu Ammonis 1 (CA1), CA2, CA3, Dentate Gyrus (DG) & CA4 and the tail of the left hippocampal formation from coronal images, blinded to group allocation. Intracranial Volume (ICV) was assessed using unified segmentation as implemented in SPM8 (Ashburner&Friston, 2005). Subfield volumes were transformed to z-scores. Results: Mean 6 SD age was 74 6 8 years in MCI/AD patients, and 68 6 3 in controls. Mean MMSE scores were 25 6 3 and 29 6 1, respectively. Regression analyses, adjusted for age, sex and ICV, with z-scores of subfield volumes as dependent variable showed (borderline) significant differences between patients and controls for CA1 (B ¼ -0.88, 95%CI -1.50 to -0.26; P ¼ 0.007), DG&CA4 (B ¼ -0.87, 95%CI -1.56 to -0.19; P ¼ 0.014), CA3 (B ¼ -0.80, 95%CI -1.60 to 0.001; P ¼ 0.050), and SUB (B ¼ -0.77, 95% CI -1.49 to -0.049; P ¼ 0.037). No significant differences in subfield volumes were found for ERC (B ¼ -0.34, 95%CI -1.11 to 0.43; P ¼ 0.38), CA2 (B ¼ -0.50, 95% CI -1.28 to 0.29; P ¼ 0.21), and tail (B ¼ 0.01, 95%CI -0.81 to 0.83; P ¼ 0.98). Conclusions: This study gives preliminary evidence that the CA1,
CA3, DG & CA4, and subiculum are affected in MCI and early AD compared to normal aging. Future 7T studies may be helpful in further entangling the role of hippocampal subfields in AD.
IC-P-117
DIVERGING PIB AND FDG COVARIANCE PATTERNS ACROSS CLINICAL VARIANTS OF ALZHEIMER’S DISEASE
Manja Lehmann1, Pia Ghosh2, Cindee Madison3, Chiara Corbetta3, Andrea Long4, Bruce Miller2, William Jagust3, Gil Rabinovici2, 1UCSF Memory and Aging Center, San Francisco, California, United States; 2 UCSF Memory and Aging Center, San Francisco, California, United States; 3Helen Wills Neuroscience Institute, UC Berkeley, Berkeley, California, United States; 4Lawrence Berkeley National Laboratory, Berkeley, California, United States. Background: Patients with Alzheimer’s disease (AD) may present with different clinical phenotypes, characterized by either predominant memory, visual or language deficits. The factors driving this heterogeneity in AD are not well understood. Using a covariance approach, the current study aimed to assess the relationship between amyloid deposition, glucose metabolism and clinical variants of AD. Methods: The study included 43 patients with probable AD (17 early-onset typical AD (EOAD), 13 language (AD-LANG) and 13 visual variants (AD-VIS), age ¼ 62.0 (7.1) years, 55% male). In a previous study, 3 peak atrophy voxels that showed selective grey matter atrophy in each AD variant compared with the other two were identified: right middle frontal gyrus in EOAD, left superior temporal sulcus in AD-
Figure. Overlap between FDG correlation maps (top) and PIB correlation maps (bottom). Overlap maps show correlations of glucose hypometabolism and amyloid deposition with FDG and PIB uptake, respectively, in the EOAD ROI (red), AD-LANG ROI (blue), and AD-VIS ROI (green). Shown are statistically significant t scores after multiple comparisons correction (FWE at P <0.05).
Alzheimer’s Imaging Consortium Posters: IC-P
SPECT imaging. As there are no non-radioactive Tc isotopes, Re complexes are often synthesised as surrogates to the corresponding 99m Tc analogues for preliminary assessment. A range of novel Re and 99m Tc complexes have been synthesized. These compounds have been assessed for their ability to bind to amyloid in human brain tissue and for preferential uptake in the APP/PS1 mouse of AD. Results: We have developed synthetic methods to prepare [Tc(CO)3(H 2 O)3]+ from [TcO 4]- under aqueous conditions using kit based formulations. This core has then been coordinated to an organic framework specifially designed to bind to amyloid plaques. We have used the intrinsic fluorescence of these compounds to show that they can bind to Ab in human brain slices from AD subjects (fig). Appraisal of the compounds in the APP/PS1 mice is currently ongoing. Conclusions: SPECT is not as quantitative as PET imaging and therefore we do not envisage a scenario wheret SPECT would replace PET imaging. SPECT would supplement PET imaging by acting as a prescreen for the general population to identify individuals at risk of developing AD. This diagnosis this could then be confirmed by PET imaging. We have developed new amyloid binding that have the potential to be effective SPECT imaging agents.
IC-P-116
ALZHEIMER’S DISEASE–RELATED CHANGES IN SUBFIELDS OF THE HIPPOCAMPAL FORMATION USING 7T MRI
Laura Wisse, Geert Jan Biessels, Sophie Heringa, H. Kuijf, H. Koek, Peter Luijten, Mirjam Geerlings, University Medical Center Utrecht, Utrecht, the Netherlands. Background: Post-mortem studies indicate that subfields of the hippocampal formation are differentially affected by normal aging and Alzheimer’s Disease (AD). Recent studies on 3-4Tesla MRI confirm these observations, but mostly assessed the subfields only in the body of the hippocampus or assessed only three subfields. We developed and validated a protocol using isotropic voxels (0.70 mm 3) at 7T MRI to delineate subfields of the hippocampal formation along its full length. In this pilot study using this protocol, we examined whether subfield volumes differ between patients with Mild Cognitive Impairment (MCI)/AD and older persons with normal cognition. Methods: 17 patients (59% women) with MCI (n ¼ 10) or AD (n ¼ 7) were recruited at the UMC Utrecht and 17 elders (65% women) with normal cognition were recruited through GPs in the region. Subjects were scanned with a T2 sequence on a 7T MRI whole body scanner (Philips Healthcare). One rater (LEMW) manually outlined the Entorhinal Cortex (ERC), subiculum (SUB), Cornu Ammonis 1 (CA1), CA2, CA3, Dentate Gyrus (DG) & CA4 and the tail of the left hippocampal formation from coronal images, blinded to group allocation. Intracranial Volume (ICV) was assessed using unified segmentation as implemented in SPM8 (Ashburner&Friston, 2005). Subfield volumes were transformed to z-scores. Results: Mean 6 SD age was 74 6 8 years in MCI/AD patients, and 68 6 3 in controls. Mean MMSE scores were 25 6 3 and 29 6 1, respectively. Regression analyses, adjusted for age, sex and ICV, with z-scores of subfield volumes as dependent variable showed (borderline) significant differences between patients and controls for CA1 (B ¼ -0.88, 95%CI -1.50 to -0.26; P ¼ 0.007), DG&CA4 (B ¼ -0.87, 95%CI -1.56 to -0.19; P ¼ 0.014), CA3 (B ¼ -0.80, 95%CI -1.60 to 0.001; P ¼ 0.050), and SUB (B ¼ -0.77, 95% CI -1.49 to -0.049; P ¼ 0.037). No significant differences in subfield volumes were found for ERC (B ¼ -0.34, 95%CI -1.11 to 0.43; P ¼ 0.38), CA2 (B ¼ -0.50, 95% CI -1.28 to 0.29; P ¼ 0.21), and tail (B ¼ 0.01, 95%CI -0.81 to 0.83; P ¼ 0.98). Conclusions: This study gives preliminary evidence that the CA1,
CA3, DG & CA4, and subiculum are affected in MCI and early AD compared to normal aging. Future 7T studies may be helpful in further entangling the role of hippocampal subfields in AD.
IC-P-117
DIVERGING PIB AND FDG COVARIANCE PATTERNS ACROSS CLINICAL VARIANTS OF ALZHEIMER’S DISEASE
Manja Lehmann1, Pia Ghosh2, Cindee Madison3, Chiara Corbetta3, Andrea Long4, Bruce Miller2, William Jagust3, Gil Rabinovici2, 1UCSF Memory and Aging Center, San Francisco, California, United States; 2 UCSF Memory and Aging Center, San Francisco, California, United States; 3Helen Wills Neuroscience Institute, UC Berkeley, Berkeley, California, United States; 4Lawrence Berkeley National Laboratory, Berkeley, California, United States. Background: Patients with Alzheimer’s disease (AD) may present with different clinical phenotypes, characterized by either predominant memory, visual or language deficits. The factors driving this heterogeneity in AD are not well understood. Using a covariance approach, the current study aimed to assess the relationship between amyloid deposition, glucose metabolism and clinical variants of AD. Methods: The study included 43 patients with probable AD (17 early-onset typical AD (EOAD), 13 language (AD-LANG) and 13 visual variants (AD-VIS), age ¼ 62.0 (7.1) years, 55% male). In a previous study, 3 peak atrophy voxels that showed selective grey matter atrophy in each AD variant compared with the other two were identified: right middle frontal gyrus in EOAD, left superior temporal sulcus in AD-
Figure. Overlap between FDG correlation maps (top) and PIB correlation maps (bottom). Overlap maps show correlations of glucose hypometabolism and amyloid deposition with FDG and PIB uptake, respectively, in the EOAD ROI (red), AD-LANG ROI (blue), and AD-VIS ROI (green). Shown are statistically significant t scores after multiple comparisons correction (FWE at P <0.05).