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Amyloid imaging with Pittsburgh Compound-B in late-life depression
Abstracts: PET and MRI / 1 (Suppl 1) (2005)
S85
Methods: 12 AD patients and 9 control subjects had 11C-PIB PET with online arterial sampling and 9 AD patients and 9 controls had 11CPK11195 PET. Spectral analysis was used to generate parametric maps of regional cerebral 11C-PIB binding. Compartmental analysis was used to generate parametric maps of regional brain 11C-PK11195 binding, a nonspecific tissue reference input function being defined with cluster analysis. Object maps were created by segmenting individual MRIs and spatially transforming the grey matter images and PET scans into standard stereotaxic MNI space on which a probabilistic atlas was superimposed. Significant clusters of increased 11C-PIB and 11C-PK11195 binding in AD were localised with SPM99 software. A correlation coefficient map was then generated from the coregistered Alzheimer PK and PIB scans with SSM software. Results: PIB-SPM PK-SPM Correlation map 11C-PIB PET showed significant 2-3 fold increases in amyloid load in the frontal, temporal, parietal, occipital association cortex of AD patients (p⬍0.0001) [Fig1]. 11C-PK11195 PET detected an increase in frontal, temporal, parietaletal, and occipital microglial activation in AD (p⬍0.05) [Fig2]. The correlation map shows voxels where there are parallel increases in 11C-PIB and 11C-PK11195 uptake (p⬍0.05, r⫽0.68)[Fig3] in 7 AD patients who had both scans. Conclusion: Increased amyloid load in cortical association areas in Alzheimer’s disease positively correlates with the presence of increased microglial activation. This provides a rationale for examining both these pathologies when studying the efficacy of putative anti-amyloid agents.
O1-03-08
AMYLOID IMAGING WITH PITTSBURGH COMPOUND-B IN LATE-LIFE DEPRESSION
Carolyn C. Meltzer, Meryl A. Butters, William E. Klunk, Chester A. Mathis, Julie C. Price, Brian J. Lopresti, Charles F. Reynolds, Stephen T. DeKosky; University of Pittsburgh, Pittsburgh, PA, USA Background: Cognitive impairment—whether reversible or irreversible by antidepressant therapy—appears to be the single strongest predictor of the development of Alzheimer’s disease (AD) in late-life depressed patients. Increasing evidence supports the concept that latelife, and particularly late-onset, depression may be a prodrome of AD. The development of Pittsburgh Compound-B (PIB) presents the opportunity to investigate the relationship among cognitive impairment, subclinical AD pathology, and dementia risk in patients with depression of late life. Objective: To investigate the link between late-life depression and AD using PET imaging and the beta-amyloid binding agent, PIB. Methods: Following injection of 15mCi PIB, dynamic PET imaging (90min) was performed with arterial sampling in remitted depressed subjects using a Siemens HR⫹ tomograph. These data were compared with similarly acquired PIB data in AD and age-matched healthy controls. Regional time-activity data were generated from magnetic resonance imaging (MRI)-guided regions-of-interest, including the posterior cingulate, prefrontal cortex, mesial temporal cortex, parietal cortex. Compartmental modeling and graphical analyses (Patlak and Logan methods) were applied to the data for determination of regional PIB distribution volume (DV); these were normalized to the cerebellar DV (reference region, in which amyloid plaques are not present) to yield DV ratios (DVRs). MRI-based partial volume correction was applied to regional DVR values. Results: Preliminary PET studies show elevated PIB binding relative to controls in non-demented late-life depressed subjects. Conclusion: Preliminary data support the hypothesis that late-life depression may herald the development of AD, as evidenced by cortical PIB retention which is reflective of the presence of amyloid deposition. Supported by PHS grants MH52247, MH43832, AG05133, AG18402, MH070729
S85
Methods: 12 AD patients and 9 control subjects had 11C-PIB PET with online arterial sampling and 9 AD patients and 9 controls had 11CPK11195 PET. Spectral analysis was used to generate parametric maps of regional cerebral 11C-PIB binding. Compartmental analysis was used to generate parametric maps of regional brain 11C-PK11195 binding, a nonspecific tissue reference input function being defined with cluster analysis. Object maps were created by segmenting individual MRIs and spatially transforming the grey matter images and PET scans into standard stereotaxic MNI space on which a probabilistic atlas was superimposed. Significant clusters of increased 11C-PIB and 11C-PK11195 binding in AD were localised with SPM99 software. A correlation coefficient map was then generated from the coregistered Alzheimer PK and PIB scans with SSM software. Results: PIB-SPM PK-SPM Correlation map 11C-PIB PET showed significant 2-3 fold increases in amyloid load in the frontal, temporal, parietal, occipital association cortex of AD patients (p⬍0.0001) [Fig1]. 11C-PK11195 PET detected an increase in frontal, temporal, parietaletal, and occipital microglial activation in AD (p⬍0.05) [Fig2]. The correlation map shows voxels where there are parallel increases in 11C-PIB and 11C-PK11195 uptake (p⬍0.05, r⫽0.68)[Fig3] in 7 AD patients who had both scans. Conclusion: Increased amyloid load in cortical association areas in Alzheimer’s disease positively correlates with the presence of increased microglial activation. This provides a rationale for examining both these pathologies when studying the efficacy of putative anti-amyloid agents.
O1-03-08
AMYLOID IMAGING WITH PITTSBURGH COMPOUND-B IN LATE-LIFE DEPRESSION
Carolyn C. Meltzer, Meryl A. Butters, William E. Klunk, Chester A. Mathis, Julie C. Price, Brian J. Lopresti, Charles F. Reynolds, Stephen T. DeKosky; University of Pittsburgh, Pittsburgh, PA, USA Background: Cognitive impairment—whether reversible or irreversible by antidepressant therapy—appears to be the single strongest predictor of the development of Alzheimer’s disease (AD) in late-life depressed patients. Increasing evidence supports the concept that latelife, and particularly late-onset, depression may be a prodrome of AD. The development of Pittsburgh Compound-B (PIB) presents the opportunity to investigate the relationship among cognitive impairment, subclinical AD pathology, and dementia risk in patients with depression of late life. Objective: To investigate the link between late-life depression and AD using PET imaging and the beta-amyloid binding agent, PIB. Methods: Following injection of 15mCi PIB, dynamic PET imaging (90min) was performed with arterial sampling in remitted depressed subjects using a Siemens HR⫹ tomograph. These data were compared with similarly acquired PIB data in AD and age-matched healthy controls. Regional time-activity data were generated from magnetic resonance imaging (MRI)-guided regions-of-interest, including the posterior cingulate, prefrontal cortex, mesial temporal cortex, parietal cortex. Compartmental modeling and graphical analyses (Patlak and Logan methods) were applied to the data for determination of regional PIB distribution volume (DV); these were normalized to the cerebellar DV (reference region, in which amyloid plaques are not present) to yield DV ratios (DVRs). MRI-based partial volume correction was applied to regional DVR values. Results: Preliminary PET studies show elevated PIB binding relative to controls in non-demented late-life depressed subjects. Conclusion: Preliminary data support the hypothesis that late-life depression may herald the development of AD, as evidenced by cortical PIB retention which is reflective of the presence of amyloid deposition. Supported by PHS grants MH52247, MH43832, AG05133, AG18402, MH070729