- Email: [email protected]
O1-04-07
Oral O1-04-06: Early Detection and Diagnosis 1 and elderly normal controls (NC), and to estimate the number of AD and MCI patients needed to evaluate a putative disease-slowing treatment in a six-month clinical trial, using PET images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.eduADNI). Methods: Baseline and approximately sixmonth follow-up ADNI PET images were compared in separate analyses of 16 AD patients, 27 MCI patients and 27 NC using SPM5. Using the atlas coordinate with the maximally significant CMRgl decline in the respective AD and MCI comparison, power analyses were performed to estimate the number of patients needed to evaluate a putative primary prevention therapy in a six-month multi-center clinical trial. Results: There was a trend for approximately six-month MMSE declines in the AD patients (P⫽0.06) and MCI patients (P⫽0.06) but not in the NC (P⫽0.86). The AD patients had six-month CMRgl declines in left temporal, parietal and precuneus regions (maximal reduction 3.0%), the MCI patients had six-month CMRgl declines in bilateral temporal, right parietal and right frontal regions (maximal reduction 2.0%), and the NC had had six-month declines in the left temporal cortex (P⬍0.001, uncorrected for multiple comparisons). Using the maximal, left temporal CMRgl declines in each patient group, we estimate the need for at least 224 AD patients or 642 MCI patients per treatment arm to detect a putative disease-slowing treatment efficacy to reduce sixmonth CMRgl declines by 25% with 80% power (one-tailed P⫽0.005, uncorrected for multiple comparisons) in a multi-center clinical trial. Conclusions: This study provides preliminary information about sixmonth CMRgl declines in AD and MCI patients and a preliminary estimate of the number of patients needed to detect CMRgl effects in six-month clinical trials of putative disease-slowing treatments. O1-04-06
CORRELATION OF MEMORY DYSFUNCTION AND AMYLOID BURDEN IN MILD COGNITIVE IMPAIRMENT
Christopher C. Rowe1, Kerryn Pike2, Greg Savage2, Steven Ng1, William Browne1, Graeme O’Keefe1, Henri J. Tochon-Danguy1, J. Gordon Chan1, Colin L. Masters3, Victor L. Villemagne1,3, 1Austin Hospital, Melbourne, VIC, Australia; 2Monash University, Melbourne, VIC, Australia; 3University of Melbourne, Melbourne, VIC, Australia. Contact e-mail: [email protected] Background: Mild cognitive impairment (MCI) carries a high risk of conversion to Alzheimer’s disease (AD). The relationship between amyloid (A) burden and severity of impairment in AD is controversial and has not been explored in MCI. Objectives: We examined the relationship between memory impairment and A burden as measured by PIB-PET. Methods: 34 healthy controls (HC) (age 71 ⫾ 7; MMSE ⬎28), 44 MCI subjects (age 72 ⫾ 9; MMSE 26.6 ⫾ 3) and 44 subjects with mild to moderate AD (age 73 ⫾ 10; MMSE 21.3 ⫾ 4) were studied. All subjects underwent cognitive assessment including MMSE and California Verbal Learning Test II long delay (CVLT). A burden was quantified using Standardized Uptake Value normalized to cerebellar cortex (SUVR) 40-70 min.PI. The mean of frontal, posterior cingulate, parietal, lateral temporal and occipital regions was used for analysis. Results: SUVR was 1.40 ⫾ 0.33 in HC, 1.81 ⫾ 0.59 in MCI and 2.39 ⫾ 0.39 in AD and correlated negatively across all subjects with cognitive measures (MMSE r ⫽ -0.43, p⬍0.0001). When groups were examined separately, only the MCI cohort showed a correlation with cognition (CVLT r ⫽ -0.53, p ⬍ 0.001). At a SUVR thresh-hold of 1.6 (the 75th percentile of HC), cortical PIB binding was present in 100% of AD, 60% of MCI and 23% of HC. In MCI, but not in HC, PIB ⫹ve subjects performed worse than PIB -ve subjects on memory measures (CVLT 2.9 ⫾ 0.9 vs 7.2 ⫾ 1.1, p ⫽ 0.004). Correlation between A and memory impairment in MCI persisted after removing the PIB -ve subjects (CVLT r ⫽ -0.49, p ⫽ 0.01). Conclusions: Our data supports a pathogenic role for A accumulation in AD by showing a relationship to mild cognitive impairment. This relationship is lost in
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later stages of disease as dementia develops. These findings may have implications for anti-amyloid therapy. O1-04-07
CSF AND MRI PERFUSION BIOMARKERS IN MIDDLE-AGED ADULTS AT RISK FOR ALZHEIMER’S DISEASE: INFLUENCE OF APOE4 ALLELE
Cynthia M. Carlsson1,2, Zhifei Wen1, Guofan Xu1, Howard A. Rowley1, George C. Newman3, Jodi H. Barnet1, Carey E. Gleason1,2, Luigi Puglielli1,2, Karl K. Vigen1, Alan B. McMillan1, Rachel D. McKinsey1, John M. Ollinger1, Mark A. Sager1, Bruce P. Hermann1, Sanjay Asthana1,2, Sean B. Fain1, Sterling C. Johnson1,2, 1University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 2Madison Veterans Affairs (VA) Geriatric Research, Education and Clinical Center (GRECC), Madison, WI, USA; 3Albert Einstein Medical Center, Philadelphia, PA, USA. Contact e-mail: [email protected] Background: APOE4 allele and vascular risk factors in midlife are independently associated with an increased risk of Alzheimer’s disease (AD) in later life. It is unclear how APOE4 and vascular factors interact to affect -amyloid (A) metabolism and cerebral perfusion - two key processes that become dysregulated early in preclinical AD. Objective: To describe the relationship of APOE4 allele and vascular risk factors with CSF A levels and quantitative cerebral blood flow (qCBF) in asymptomatic adult children of persons with AD. Methods: In a crosssectional analysis of 42 middle-aged adults at risk for AD, CSF A40 and A42 (n⫽27), vascular risk factors (n⫽42), and quantitative T2*weighted perfusion MR images (n⫽20) were measured (5 subjects with both CSF and MRI). CSF A levels were measured using ELISA. T2*-weighted perfusion MR images were obtained on a GE 1.5 T MR scanner with echo planar capability. Results: Participant characteristics are shown in the Table. In subjects with CSF data, vascular risk factors did not correlate with CSF A40 or A42 levels. However, APOE4 interacted with systolic blood pressure (SBP) and body mass index (BMI) to predict CSF A levels (Figure 1). In APOE4 carriers, increased SBP and BMI were associated with CSF A40 and A42 levels and A40/42 ratios suggestive of preclinical disease progression. This relationship was not noted in APOE4 non-carriers (Figure 1). In MR perfusion analyses (n⫽20), APOE4 carriers had lower qCBF in the middle temporal gyrus compared to non-carriers (APOE4 carriers 39.3 ⫾ 18.8 vs. APOE4 non-carriers 59.6 ⫾ 15.9 ml/100g/min, p⫽0.023, Figure 2). While APOE group differences in qCBF did not reach statistical significance in the superior frontal gyrus, parietal lobe, posterior cingulate, parahippocampus, and hippocampus (all p⬎0.3), the overall pattern suggests lower qCBF in these regions in APOE4 carriers compared to non-carriers (Figure 2). Conclusions: In asymptomatic middle-aged adult children of persons with AD, APOE4 allele may influence the relationship of vascular risk factors with A metabolism as well as CBF in brain areas known to be hypometabolic in symptomatic AD. Further studies are needed to confirm and clarify the clinical implications of these findings. Funded by NIA K23AG026752. Table Participant Characteristics Characteristic (nⴝ42)
Value (Mean ⴞ SD)
Age, y Women, n (%) APOE4 carriers, n (%) Total cholesterol, mg/dL (mmol/L) LDL cholesterol, mg/dL (mmol/L) Systolic blood pressure, mm Hg Body mass index (BMI), kg/m2 Diabetes mellitus, n (%) Current tobacco use, n (%)
54.5 ⫾ 8.0 29 (69) 15 (36) 195.8 ⫾ 35.2 (5.07 ⫾ 0.9) 107.8 ⫾ 37.9 (2.8 ⫾ 1.0) 119.0 ⫾ 13.0 27.2 ⫾ 5.0 0 (0) 4 (10)
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Oral O1-05-01: Early Detection and Diagnosis 2 SUNDAY, JUNE 10, 2007 ORAL O1-05 EARLY DETECTION AND DIAGNOSIS 2 O1-05-01
CORTICAL AMYLOID DEPOSITION RELATED TO FAILURE OF HIPPOCAMPAL ACTIVATION
Reisa Sperling1, Pete LaViolette2, Eli White1, J. Alex Becker2, Erin Moran2, Matt Gregas3, William Klunk4, Chet Mathis4, Julie Price4, Alan Fischman2, Dennis Selkoe1, Dorene Rentz1, Keith Johnson2, 1 Brigham and Women’s Hospital, Boston, MA, USA; 2Massachusetts General Hospital, Boston, MA, USA; 3Harvard School of Public Health, Boston, MA, USA; 4University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: [email protected]
O1-04-08
PIB AND MRI PROVIDE COMPLEMENTARY INFORMATION IN IMAGING OF AD AND MCI
Clifford R. Jack, Val Lowe, Bradley Kemp, Maria Shiung, Stephen Weigand, David Knopman, Bradley Boeve, Ronald Petersen, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: The development of amyloid plaque (or plaque and tangle) labeling compounds like Pittsburgh Compound -B (PIB) has revolutionized the approach to diagnosis of Alzheimer’s Disease (AD). Early diagnostic imaging comparisons have been between PIB and FDG PET with only a single published PIB - Magnetic Resonance Imaging (MRI) comparison report to date. We report preliminary results of an ongoing study comparing MRI and PIB in the same subjects spanning the cognitive spectrum from normal to demented. Objective: To compare structural MRI and PIB measures in prevalent normal aging, amnestic Mild Cognitive Impairment (aMCI), and AD. Methods: Thirteen cognitively normal (CN) elderly, 13 aMCI, and 7 AD subjects underwent PIB and structural MRI. We measured global PIB cortical to cerebellar uptake ratio and hippocampal volumes (HV) corrected for age, gender, and head size in all subjects. Results: PIB ratios were ordered AD ⬎ aMCI ⬎ CN, and group-wise ordering of HV was reversed. Group-wise separation by PIB and HV was comparable. Mean (SD) PIB ratios in CN, aMCI, and AD were 1.1 (0.1), 1.5 (0.3), 1.9 (0.3), respectively. HV were 0.0 (1.3), - 0.9 (0.6), -2.2 (0.6), respectively. For both modalities, CN and AD subjects were completely separated while aMCI subjects overlapped both the CN and AD range. There was a single exception - one CN subject whose HV was in the AD range. All pair-wise comparisons (CN vs aMCI, CN vs AD, aMCI vs AD) were significant (p ⬍ 0.05) for both PIB and MRI. Conclusions: The two modalities supply independent information about mechanisms relevant to dementia: PIB is an in vivo measure of plaque burden, and structural MRI a measure of neuronal and synaptic damage. Although the inverse correlation was high (r -0.65, p ⫽ 0.003), ranking of individual subjects by PIB ratio and HV was not monotonically inverse, indicating that the two modalities provide complimentary diagnostic information. And, combining the two modalities should provide unique insight into the multifactorial mechanisms underlying dementias. Acknowledgments: AG11378, AG06786, AG16574, Robert and Clarice Smith and Abigail Van Buren AD Research Program
Background: Amyloid is thought to be an inciting factor in the pathophysiological process of Alzheimer’s disease (AD). Autopsy data, however, has revealed relatively weak correlations between the amount and location of amyloid plaque burden and dementia severity, while in vitro assays of synaptic function and animal experiments have suggested that amount of amyloid may acutely modulate memory function. Our previous fMRI studies have shown that AD patients demonstrate significantly decreased hippocampal activation compared to normal older controls. In this study, we wanted to examine the relationship of amyloid burden to the hippocampal activation across a spectrum of cognitive impairment. Objective(s): To investigate the relationship of amyloid deposition, as assessed by positron emission tomography (PET) with Pittsburgh Imaging Compound B (PIB), to memory-related functional magnetic resonance imaging (fMRI) patterns of activation. Methods: Seventeen older subjects (seven controls (CDR 0); five subjects with mild cognitive impairment (MCI; CDR 0.5) and five mild AD patients (CDR 1.0)) were imaged with both fMRI during an associative face-name encoding task and PIB-PET acquired over 60 minutes after injection of 10-15 mCi C11-PIB. fMRI datasets were analyzed with two-sample t-tests in SPM2. Functional connectivity was assessed with psychophysiological interactions (PPI). Specific PIB binding was calculated using the Logan graphical analysis method yielding a distribution volume ratio (DVR) with cerebellar gray as reference. Subjects were classified as PIB⫹ if the cortical DVR was ⬎1.05 and PIB- if only non-specific binding was present. Level of PIB binding was entered as a regressor into the functional connectivity maps. Results: Ten of the 17 subjects were PIB⫹, while seven subjects were PIB-. PIB⫹ subjects showed significantly decreased activation in the right hippocampus (p⬍0.003), compared to PIB- subjects. This finding remained significant, even when CDR score was entered as a co-variate. Furthermore, the level of PIB binding in cortical regions, in particular the precuneus, was correlated with decreased connectivity between precuneus and hippocampal regions (p⬍0.007). Conclusions: These preliminary results support the hypothesis that cortical amyloid deposition, particularly in medial parietal regions, is related to hippocampal dysfunction. O1-05-02
AGE AND ALZHEIMER’S DISEASE RELATED EFFECTS ON CEREBRAL BLOOD FLOW AND ARTERIAL TRANSIT TIME OF POSTERIOR CINGULATE CORTEX WITH SERIAL ARTERIAL SPIN LABELING MRI
Xiaoping Zhu1,2, Norbert Schuff1,2, Matthias Gunther3, David Feinberg3, Yu Zhang1,2, Geon-ho Jahng1,2, Michael W. Weiner1,2, 1 Department of Radiology, UCSF, San Francisco, CA, USA; 2Center for Imaging of Neurodegenerative Diseases, VA Medical Center, San Francisco, CA, USA; 3Advanced MRI Technologies, Sebastopol, CA, USA. Contact e-mail: [email protected] Background: Previous studies using PET and SPECT reported substantial reduction of cerebral blood flow (CBF) of the posterior cingulate (PC) in Alzheimer disease (AD) and mild cognitive impairment (MCI). However, these methods use ionizing radiation and quantification of CBF remains a
CORRELATION OF MEMORY DYSFUNCTION AND AMYLOID BURDEN IN MILD COGNITIVE IMPAIRMENT
Christopher C. Rowe1, Kerryn Pike2, Greg Savage2, Steven Ng1, William Browne1, Graeme O’Keefe1, Henri J. Tochon-Danguy1, J. Gordon Chan1, Colin L. Masters3, Victor L. Villemagne1,3, 1Austin Hospital, Melbourne, VIC, Australia; 2Monash University, Melbourne, VIC, Australia; 3University of Melbourne, Melbourne, VIC, Australia. Contact e-mail: [email protected] Background: Mild cognitive impairment (MCI) carries a high risk of conversion to Alzheimer’s disease (AD). The relationship between amyloid (A) burden and severity of impairment in AD is controversial and has not been explored in MCI. Objectives: We examined the relationship between memory impairment and A burden as measured by PIB-PET. Methods: 34 healthy controls (HC) (age 71 ⫾ 7; MMSE ⬎28), 44 MCI subjects (age 72 ⫾ 9; MMSE 26.6 ⫾ 3) and 44 subjects with mild to moderate AD (age 73 ⫾ 10; MMSE 21.3 ⫾ 4) were studied. All subjects underwent cognitive assessment including MMSE and California Verbal Learning Test II long delay (CVLT). A burden was quantified using Standardized Uptake Value normalized to cerebellar cortex (SUVR) 40-70 min.PI. The mean of frontal, posterior cingulate, parietal, lateral temporal and occipital regions was used for analysis. Results: SUVR was 1.40 ⫾ 0.33 in HC, 1.81 ⫾ 0.59 in MCI and 2.39 ⫾ 0.39 in AD and correlated negatively across all subjects with cognitive measures (MMSE r ⫽ -0.43, p⬍0.0001). When groups were examined separately, only the MCI cohort showed a correlation with cognition (CVLT r ⫽ -0.53, p ⬍ 0.001). At a SUVR thresh-hold of 1.6 (the 75th percentile of HC), cortical PIB binding was present in 100% of AD, 60% of MCI and 23% of HC. In MCI, but not in HC, PIB ⫹ve subjects performed worse than PIB -ve subjects on memory measures (CVLT 2.9 ⫾ 0.9 vs 7.2 ⫾ 1.1, p ⫽ 0.004). Correlation between A and memory impairment in MCI persisted after removing the PIB -ve subjects (CVLT r ⫽ -0.49, p ⫽ 0.01). Conclusions: Our data supports a pathogenic role for A accumulation in AD by showing a relationship to mild cognitive impairment. This relationship is lost in
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later stages of disease as dementia develops. These findings may have implications for anti-amyloid therapy. O1-04-07
CSF AND MRI PERFUSION BIOMARKERS IN MIDDLE-AGED ADULTS AT RISK FOR ALZHEIMER’S DISEASE: INFLUENCE OF APOE4 ALLELE
Cynthia M. Carlsson1,2, Zhifei Wen1, Guofan Xu1, Howard A. Rowley1, George C. Newman3, Jodi H. Barnet1, Carey E. Gleason1,2, Luigi Puglielli1,2, Karl K. Vigen1, Alan B. McMillan1, Rachel D. McKinsey1, John M. Ollinger1, Mark A. Sager1, Bruce P. Hermann1, Sanjay Asthana1,2, Sean B. Fain1, Sterling C. Johnson1,2, 1University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 2Madison Veterans Affairs (VA) Geriatric Research, Education and Clinical Center (GRECC), Madison, WI, USA; 3Albert Einstein Medical Center, Philadelphia, PA, USA. Contact e-mail: [email protected] Background: APOE4 allele and vascular risk factors in midlife are independently associated with an increased risk of Alzheimer’s disease (AD) in later life. It is unclear how APOE4 and vascular factors interact to affect -amyloid (A) metabolism and cerebral perfusion - two key processes that become dysregulated early in preclinical AD. Objective: To describe the relationship of APOE4 allele and vascular risk factors with CSF A levels and quantitative cerebral blood flow (qCBF) in asymptomatic adult children of persons with AD. Methods: In a crosssectional analysis of 42 middle-aged adults at risk for AD, CSF A40 and A42 (n⫽27), vascular risk factors (n⫽42), and quantitative T2*weighted perfusion MR images (n⫽20) were measured (5 subjects with both CSF and MRI). CSF A levels were measured using ELISA. T2*-weighted perfusion MR images were obtained on a GE 1.5 T MR scanner with echo planar capability. Results: Participant characteristics are shown in the Table. In subjects with CSF data, vascular risk factors did not correlate with CSF A40 or A42 levels. However, APOE4 interacted with systolic blood pressure (SBP) and body mass index (BMI) to predict CSF A levels (Figure 1). In APOE4 carriers, increased SBP and BMI were associated with CSF A40 and A42 levels and A40/42 ratios suggestive of preclinical disease progression. This relationship was not noted in APOE4 non-carriers (Figure 1). In MR perfusion analyses (n⫽20), APOE4 carriers had lower qCBF in the middle temporal gyrus compared to non-carriers (APOE4 carriers 39.3 ⫾ 18.8 vs. APOE4 non-carriers 59.6 ⫾ 15.9 ml/100g/min, p⫽0.023, Figure 2). While APOE group differences in qCBF did not reach statistical significance in the superior frontal gyrus, parietal lobe, posterior cingulate, parahippocampus, and hippocampus (all p⬎0.3), the overall pattern suggests lower qCBF in these regions in APOE4 carriers compared to non-carriers (Figure 2). Conclusions: In asymptomatic middle-aged adult children of persons with AD, APOE4 allele may influence the relationship of vascular risk factors with A metabolism as well as CBF in brain areas known to be hypometabolic in symptomatic AD. Further studies are needed to confirm and clarify the clinical implications of these findings. Funded by NIA K23AG026752. Table Participant Characteristics Characteristic (nⴝ42)
Value (Mean ⴞ SD)
Age, y Women, n (%) APOE4 carriers, n (%) Total cholesterol, mg/dL (mmol/L) LDL cholesterol, mg/dL (mmol/L) Systolic blood pressure, mm Hg Body mass index (BMI), kg/m2 Diabetes mellitus, n (%) Current tobacco use, n (%)
54.5 ⫾ 8.0 29 (69) 15 (36) 195.8 ⫾ 35.2 (5.07 ⫾ 0.9) 107.8 ⫾ 37.9 (2.8 ⫾ 1.0) 119.0 ⫾ 13.0 27.2 ⫾ 5.0 0 (0) 4 (10)
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Oral O1-05-01: Early Detection and Diagnosis 2 SUNDAY, JUNE 10, 2007 ORAL O1-05 EARLY DETECTION AND DIAGNOSIS 2 O1-05-01
CORTICAL AMYLOID DEPOSITION RELATED TO FAILURE OF HIPPOCAMPAL ACTIVATION
Reisa Sperling1, Pete LaViolette2, Eli White1, J. Alex Becker2, Erin Moran2, Matt Gregas3, William Klunk4, Chet Mathis4, Julie Price4, Alan Fischman2, Dennis Selkoe1, Dorene Rentz1, Keith Johnson2, 1 Brigham and Women’s Hospital, Boston, MA, USA; 2Massachusetts General Hospital, Boston, MA, USA; 3Harvard School of Public Health, Boston, MA, USA; 4University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: [email protected]
O1-04-08
PIB AND MRI PROVIDE COMPLEMENTARY INFORMATION IN IMAGING OF AD AND MCI
Clifford R. Jack, Val Lowe, Bradley Kemp, Maria Shiung, Stephen Weigand, David Knopman, Bradley Boeve, Ronald Petersen, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: The development of amyloid plaque (or plaque and tangle) labeling compounds like Pittsburgh Compound -B (PIB) has revolutionized the approach to diagnosis of Alzheimer’s Disease (AD). Early diagnostic imaging comparisons have been between PIB and FDG PET with only a single published PIB - Magnetic Resonance Imaging (MRI) comparison report to date. We report preliminary results of an ongoing study comparing MRI and PIB in the same subjects spanning the cognitive spectrum from normal to demented. Objective: To compare structural MRI and PIB measures in prevalent normal aging, amnestic Mild Cognitive Impairment (aMCI), and AD. Methods: Thirteen cognitively normal (CN) elderly, 13 aMCI, and 7 AD subjects underwent PIB and structural MRI. We measured global PIB cortical to cerebellar uptake ratio and hippocampal volumes (HV) corrected for age, gender, and head size in all subjects. Results: PIB ratios were ordered AD ⬎ aMCI ⬎ CN, and group-wise ordering of HV was reversed. Group-wise separation by PIB and HV was comparable. Mean (SD) PIB ratios in CN, aMCI, and AD were 1.1 (0.1), 1.5 (0.3), 1.9 (0.3), respectively. HV were 0.0 (1.3), - 0.9 (0.6), -2.2 (0.6), respectively. For both modalities, CN and AD subjects were completely separated while aMCI subjects overlapped both the CN and AD range. There was a single exception - one CN subject whose HV was in the AD range. All pair-wise comparisons (CN vs aMCI, CN vs AD, aMCI vs AD) were significant (p ⬍ 0.05) for both PIB and MRI. Conclusions: The two modalities supply independent information about mechanisms relevant to dementia: PIB is an in vivo measure of plaque burden, and structural MRI a measure of neuronal and synaptic damage. Although the inverse correlation was high (r -0.65, p ⫽ 0.003), ranking of individual subjects by PIB ratio and HV was not monotonically inverse, indicating that the two modalities provide complimentary diagnostic information. And, combining the two modalities should provide unique insight into the multifactorial mechanisms underlying dementias. Acknowledgments: AG11378, AG06786, AG16574, Robert and Clarice Smith and Abigail Van Buren AD Research Program
Background: Amyloid is thought to be an inciting factor in the pathophysiological process of Alzheimer’s disease (AD). Autopsy data, however, has revealed relatively weak correlations between the amount and location of amyloid plaque burden and dementia severity, while in vitro assays of synaptic function and animal experiments have suggested that amount of amyloid may acutely modulate memory function. Our previous fMRI studies have shown that AD patients demonstrate significantly decreased hippocampal activation compared to normal older controls. In this study, we wanted to examine the relationship of amyloid burden to the hippocampal activation across a spectrum of cognitive impairment. Objective(s): To investigate the relationship of amyloid deposition, as assessed by positron emission tomography (PET) with Pittsburgh Imaging Compound B (PIB), to memory-related functional magnetic resonance imaging (fMRI) patterns of activation. Methods: Seventeen older subjects (seven controls (CDR 0); five subjects with mild cognitive impairment (MCI; CDR 0.5) and five mild AD patients (CDR 1.0)) were imaged with both fMRI during an associative face-name encoding task and PIB-PET acquired over 60 minutes after injection of 10-15 mCi C11-PIB. fMRI datasets were analyzed with two-sample t-tests in SPM2. Functional connectivity was assessed with psychophysiological interactions (PPI). Specific PIB binding was calculated using the Logan graphical analysis method yielding a distribution volume ratio (DVR) with cerebellar gray as reference. Subjects were classified as PIB⫹ if the cortical DVR was ⬎1.05 and PIB- if only non-specific binding was present. Level of PIB binding was entered as a regressor into the functional connectivity maps. Results: Ten of the 17 subjects were PIB⫹, while seven subjects were PIB-. PIB⫹ subjects showed significantly decreased activation in the right hippocampus (p⬍0.003), compared to PIB- subjects. This finding remained significant, even when CDR score was entered as a co-variate. Furthermore, the level of PIB binding in cortical regions, in particular the precuneus, was correlated with decreased connectivity between precuneus and hippocampal regions (p⬍0.007). Conclusions: These preliminary results support the hypothesis that cortical amyloid deposition, particularly in medial parietal regions, is related to hippocampal dysfunction. O1-05-02
AGE AND ALZHEIMER’S DISEASE RELATED EFFECTS ON CEREBRAL BLOOD FLOW AND ARTERIAL TRANSIT TIME OF POSTERIOR CINGULATE CORTEX WITH SERIAL ARTERIAL SPIN LABELING MRI
Xiaoping Zhu1,2, Norbert Schuff1,2, Matthias Gunther3, David Feinberg3, Yu Zhang1,2, Geon-ho Jahng1,2, Michael W. Weiner1,2, 1 Department of Radiology, UCSF, San Francisco, CA, USA; 2Center for Imaging of Neurodegenerative Diseases, VA Medical Center, San Francisco, CA, USA; 3Advanced MRI Technologies, Sebastopol, CA, USA. Contact e-mail: [email protected] Background: Previous studies using PET and SPECT reported substantial reduction of cerebral blood flow (CBF) of the posterior cingulate (PC) in Alzheimer disease (AD) and mild cognitive impairment (MCI). However, these methods use ionizing radiation and quantification of CBF remains a