- Email: [email protected]
P1-267: Metabolic evidence of compensation for amyloid pathology in nondemented elderly individuals
Poster Presentations P1
Background: We previously observed robust activation in the hippocampal region in response to novel valenced stimuli during an fMRI recognition memory paradigm in healthy individuals across the lifespan. In this study, we compared activation during the memory task in elderly controls (EC) and individuals with mild cognitive impairment (MCI). Methods: In 23 right-handed participants (15 EC, 8 MCI; 16M/7F; mean age⫽71.6), neural activity was compared for novel and previously learned (familiar) items. During encoding, participants viewed 10 B/W pictures of baby and elderly faces with happy/sad expressions repeated in a block 6x, alternating with blocks of 10 circles. Participants indicated whether each face was happy or sad. After a 20-minute consolidation period, the 10 encoded faces were presented 4x each intermixed with 40 new faces (half happy, half sad). Participants identified “new” or previously learned (“old”) faces. Random effects group analysis was performed using SPM5 to compare activity in response to novel vs familiar faces. Outside the scanner, participants viewed 40 new faces (half sad, half happy), 10 faces from the encoding scan, and 80 novel faces from the recognition scan. They indicated whether each face was “new” or “old” and rated valence and arousal of each face. Results: EC showed significant activity in right fusiform and hippocampal regions in response to novel faces compared to previously learned faces (MNI coordinates FF: 40, -58, -14, T⫽8.07; pcorrected⫽.0001; HC: 22, -12, -16; T⫽5.60, puncorrected⫽.048). Significant activations were also observed in occipital and frontal cortices. A similar pattern was found in response to baby faces but did not hold for elderly faces, suggesting that arousal is important. MCI did not show increased activity in response to novel versus familiar faces in predicted regions. Groups did not significantly differ in overall reaction time/ accuracy during encoding, valence/arousal ratings or accuracy during the post-scan task, or on the Florida Affect Battery, suggesting MCIs’ affective perception was intact. MCIs were slower and less accurate during recognition scans. Conclusions: Lack of encoding-associated activity in MCIs suggests that continued studies of the functional correlates of the emotional-memory enhancement effect in the early stage of Alzheimer’s disease are warranted. MATERNAL HISTORY OF ALZHEIMER’S DISEASE PREDISPOSES TO PROGRESSIVE BRAIN HYPOMETABOLISM ON FDG-PET
N
P1-269
Lisa Mosconi, Rachel Mistur, Miroslaw Brys, Lidia Glodzik, Remigiusz Switalski, Elizabeth Pirraglia, Kenneth Rich, Wai Tsui, Mony de Leon, New York University School of Medicine, New York, NY, USA. Contact e-mail: [email protected]
AW
Background: To investigate how brain glucose metabolism is altered in response to beta-amyloid (A) deposition in nondemented elderly individuals using PET [11C]PIB and [18F]FDG. Methods: Twenty nondemented elderly individuals (age⫽73.1⫾5.7, MMSE⫽29.6⫾0.6) underwent detailed neuropsychological testing to assure normal cognition, as well as PET (PIB and FDG) and MRI scanning. PIB distribution volume ratios (DVRs) were created using a cerebellum reference region and were corrected for partial volume effects. FDG frames were averaged and normalized by mean tracer uptake in the pons. MP-RAGE T1 sequences were collected on a 1.5T scanner, and cortical regions of interest (ROI) were derived from these images and coregistered to PET data using automated procedures. We used the following ROIs (left and right separately) to explore the local relationship between PIB and FDG: superior frontal gyrus (SFG), middle frontal gyrus (MFG), precuneus (PREC), and supramarginal gyrus (SMG). Mean FDG was regressed against mean PIB within each ROI using Pearson correlation analyses. Additionally, voxel-wise exploratory analysis regressing global PIB index (derived from multiple cortical ROIs) against FDG at each voxel was implemented in SPM5 using a study specific template. Results: Age and education did not correlate with PIB or FDG. Significant positive relationships were found between FDG and PIB in anterior ROIs (left SFC R2⫽0.36, p⫽0.01; right SFC R2⫽0.28, p⫽0.02; left MFG R2⫽0.25, p⫽0.04; right MFG R2⫽0.38, p⫽0.008). Significant relationships were not found between FDG and PIB in posterior ROIs (PREC, SMG). The SPM analysis revealed significant voxel clusters in frontal cortex showing a positive relationship between global PIB and FDG (p⬍0.01, cluster size⫽100). Conclusions: These data reveal that the relationship between A pathology and glucose metabolism is not uniform across cortex in nondemented elderly individuals. Posterior regions, which show severe metabolic lesions in AD, did not show a correlation between A pathology and glucose metabolism; anterior regions, which are typically spared until late in AD progression, show that an increase in regional and global A pathology
Jeannine V. Morrone-Strupinsky, Leslie C. Baxter, Shawn Gale, Erin Baldwin, Michael Purcell, Scott Beeman, Barrow Neurological Institute, Phoenix, AZ, USA. Contact e-mail: [email protected]
D R
Elizabeth C. Mormino1, Amynta O. Hayenga1, Cindee M. Madison1, Jenny T. Kluth1, Ansgar J. Furst1, Gil D. Rabinovici2, William J. Jagust1, 1UC Berkeley, Berkeley, CA, USA; 2UC San Francisco, San Francisco, CA, USA. Contact e-mail: [email protected]
DIFFERENTIAL FMRI ACTIVITY IN RESPONSE TO NOVEL EMOTIONAL FACES IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT VERSUS ELDERLY CONTROLS
Background: Having a parent affected with late-onset Alzheimer’s disease (AD) is a risk factor for developing AD among cognitively normal (NL) subjects. We examined the association between a parental family history of AD and cerebral metabolic rates of glucose (CMRglc) on FDG-PET in NL subjects. Methods: The FDG-PET scans of 121 20-92 year-old NL, including 67 subjects with a negative family history of AD (FH-), 18 with paternal (FHp) and 36 with maternal AD (FHm), were examined to test for CMRglc differences across FH groups, and to estimate the age of onset of hypometabolism over the adult life-span.
H
METABOLIC EVIDENCE OF COMPENSATION FOR AMYLOID PATHOLOGY IN NONDEMENTED ELDERLY INDIVIDUALS
P1-268
IT
P1-267
is associated with an increase in glucose metabolism. These findings suggest that frontal regions may actively compensate in response to underlying A pathology.
W
3/1; MMSE: 25-27) and age-matched 2 HV (63-66 years; male/female: 0/2; MMSE: 29-30) participated in this study. Twice PET studies were performed on all subjects with an interval of 1.8 ⫹/- 0.4 years (mean⫹/SD). All AD patients were treated with cholinesterase inhibitor at the time of second PET study, while all MCI patients had not been given any medicine. Two MCI patients had converted to AD at the time of second PET study and one of them had started to be treated with cholinesterase inhibitor. After intravenous injection of [11C]PIB (about 370 MBq), a dynamic PET scan was performed for 90min with arterial blood sampling. All PET images were normalized to the MNI space using SPM. Distribution volume ratios (DVR), indicating the retention of [11C]PIB, were calculated on a voxel-by-voxel basis by Logan graphical analysis with the use of cerebellum as a reference brain region. Regions of interest (ROI) were drawn on the DVR images. Results: Increase in DVR of [11C]PIB of 27-43% in the cerebral cortex during interval period of two PET studies was observed in two MCI patients who had converted to AD at the time of second PET study. The change in DVR was within 6% in the cerebral cortex during period in two AD patients, two MCI patients who had remained MCI at second study, and two controls. Conclusions: Increase in beta-amyloid deposition during 2 years was shown in MCI patients who converted to AD. MCI patients showing progression of beta-amyloid accumulation in the brain may be the best candidates for amyloid modulating therapy.
T295
Background: We previously observed robust activation in the hippocampal region in response to novel valenced stimuli during an fMRI recognition memory paradigm in healthy individuals across the lifespan. In this study, we compared activation during the memory task in elderly controls (EC) and individuals with mild cognitive impairment (MCI). Methods: In 23 right-handed participants (15 EC, 8 MCI; 16M/7F; mean age⫽71.6), neural activity was compared for novel and previously learned (familiar) items. During encoding, participants viewed 10 B/W pictures of baby and elderly faces with happy/sad expressions repeated in a block 6x, alternating with blocks of 10 circles. Participants indicated whether each face was happy or sad. After a 20-minute consolidation period, the 10 encoded faces were presented 4x each intermixed with 40 new faces (half happy, half sad). Participants identified “new” or previously learned (“old”) faces. Random effects group analysis was performed using SPM5 to compare activity in response to novel vs familiar faces. Outside the scanner, participants viewed 40 new faces (half sad, half happy), 10 faces from the encoding scan, and 80 novel faces from the recognition scan. They indicated whether each face was “new” or “old” and rated valence and arousal of each face. Results: EC showed significant activity in right fusiform and hippocampal regions in response to novel faces compared to previously learned faces (MNI coordinates FF: 40, -58, -14, T⫽8.07; pcorrected⫽.0001; HC: 22, -12, -16; T⫽5.60, puncorrected⫽.048). Significant activations were also observed in occipital and frontal cortices. A similar pattern was found in response to baby faces but did not hold for elderly faces, suggesting that arousal is important. MCI did not show increased activity in response to novel versus familiar faces in predicted regions. Groups did not significantly differ in overall reaction time/ accuracy during encoding, valence/arousal ratings or accuracy during the post-scan task, or on the Florida Affect Battery, suggesting MCIs’ affective perception was intact. MCIs were slower and less accurate during recognition scans. Conclusions: Lack of encoding-associated activity in MCIs suggests that continued studies of the functional correlates of the emotional-memory enhancement effect in the early stage of Alzheimer’s disease are warranted. MATERNAL HISTORY OF ALZHEIMER’S DISEASE PREDISPOSES TO PROGRESSIVE BRAIN HYPOMETABOLISM ON FDG-PET
N
P1-269
Lisa Mosconi, Rachel Mistur, Miroslaw Brys, Lidia Glodzik, Remigiusz Switalski, Elizabeth Pirraglia, Kenneth Rich, Wai Tsui, Mony de Leon, New York University School of Medicine, New York, NY, USA. Contact e-mail: [email protected]
AW
Background: To investigate how brain glucose metabolism is altered in response to beta-amyloid (A) deposition in nondemented elderly individuals using PET [11C]PIB and [18F]FDG. Methods: Twenty nondemented elderly individuals (age⫽73.1⫾5.7, MMSE⫽29.6⫾0.6) underwent detailed neuropsychological testing to assure normal cognition, as well as PET (PIB and FDG) and MRI scanning. PIB distribution volume ratios (DVRs) were created using a cerebellum reference region and were corrected for partial volume effects. FDG frames were averaged and normalized by mean tracer uptake in the pons. MP-RAGE T1 sequences were collected on a 1.5T scanner, and cortical regions of interest (ROI) were derived from these images and coregistered to PET data using automated procedures. We used the following ROIs (left and right separately) to explore the local relationship between PIB and FDG: superior frontal gyrus (SFG), middle frontal gyrus (MFG), precuneus (PREC), and supramarginal gyrus (SMG). Mean FDG was regressed against mean PIB within each ROI using Pearson correlation analyses. Additionally, voxel-wise exploratory analysis regressing global PIB index (derived from multiple cortical ROIs) against FDG at each voxel was implemented in SPM5 using a study specific template. Results: Age and education did not correlate with PIB or FDG. Significant positive relationships were found between FDG and PIB in anterior ROIs (left SFC R2⫽0.36, p⫽0.01; right SFC R2⫽0.28, p⫽0.02; left MFG R2⫽0.25, p⫽0.04; right MFG R2⫽0.38, p⫽0.008). Significant relationships were not found between FDG and PIB in posterior ROIs (PREC, SMG). The SPM analysis revealed significant voxel clusters in frontal cortex showing a positive relationship between global PIB and FDG (p⬍0.01, cluster size⫽100). Conclusions: These data reveal that the relationship between A pathology and glucose metabolism is not uniform across cortex in nondemented elderly individuals. Posterior regions, which show severe metabolic lesions in AD, did not show a correlation between A pathology and glucose metabolism; anterior regions, which are typically spared until late in AD progression, show that an increase in regional and global A pathology
Jeannine V. Morrone-Strupinsky, Leslie C. Baxter, Shawn Gale, Erin Baldwin, Michael Purcell, Scott Beeman, Barrow Neurological Institute, Phoenix, AZ, USA. Contact e-mail: [email protected]
D R
Elizabeth C. Mormino1, Amynta O. Hayenga1, Cindee M. Madison1, Jenny T. Kluth1, Ansgar J. Furst1, Gil D. Rabinovici2, William J. Jagust1, 1UC Berkeley, Berkeley, CA, USA; 2UC San Francisco, San Francisco, CA, USA. Contact e-mail: [email protected]
DIFFERENTIAL FMRI ACTIVITY IN RESPONSE TO NOVEL EMOTIONAL FACES IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT VERSUS ELDERLY CONTROLS
Background: Having a parent affected with late-onset Alzheimer’s disease (AD) is a risk factor for developing AD among cognitively normal (NL) subjects. We examined the association between a parental family history of AD and cerebral metabolic rates of glucose (CMRglc) on FDG-PET in NL subjects. Methods: The FDG-PET scans of 121 20-92 year-old NL, including 67 subjects with a negative family history of AD (FH-), 18 with paternal (FHp) and 36 with maternal AD (FHm), were examined to test for CMRglc differences across FH groups, and to estimate the age of onset of hypometabolism over the adult life-span.
H
METABOLIC EVIDENCE OF COMPENSATION FOR AMYLOID PATHOLOGY IN NONDEMENTED ELDERLY INDIVIDUALS
P1-268
IT
P1-267
is associated with an increase in glucose metabolism. These findings suggest that frontal regions may actively compensate in response to underlying A pathology.
W
3/1; MMSE: 25-27) and age-matched 2 HV (63-66 years; male/female: 0/2; MMSE: 29-30) participated in this study. Twice PET studies were performed on all subjects with an interval of 1.8 ⫹/- 0.4 years (mean⫹/SD). All AD patients were treated with cholinesterase inhibitor at the time of second PET study, while all MCI patients had not been given any medicine. Two MCI patients had converted to AD at the time of second PET study and one of them had started to be treated with cholinesterase inhibitor. After intravenous injection of [11C]PIB (about 370 MBq), a dynamic PET scan was performed for 90min with arterial blood sampling. All PET images were normalized to the MNI space using SPM. Distribution volume ratios (DVR), indicating the retention of [11C]PIB, were calculated on a voxel-by-voxel basis by Logan graphical analysis with the use of cerebellum as a reference brain region. Regions of interest (ROI) were drawn on the DVR images. Results: Increase in DVR of [11C]PIB of 27-43% in the cerebral cortex during interval period of two PET studies was observed in two MCI patients who had converted to AD at the time of second PET study. The change in DVR was within 6% in the cerebral cortex during period in two AD patients, two MCI patients who had remained MCI at second study, and two controls. Conclusions: Increase in beta-amyloid deposition during 2 years was shown in MCI patients who converted to AD. MCI patients showing progression of beta-amyloid accumulation in the brain may be the best candidates for amyloid modulating therapy.
T295