Inverse correlations between amyloid-␤ (A␤) load measured by Pittsburgh Compound-B (PiB) positron emission tomography (PET) and cerebral metabolism using [18 F]fluoro-2-deoxy-D-glucose (FDG) in Alzheimer's disease (AD) patients, suggest local A␤-induced metabolic insults. However, this relationship has not been well studied in mild cognitive impairment (MCI) or amyloid-positive controls. Here, we explored associations of A␤ deposition with metabolism via both region-of-interest-based and voxel-based analyses in amyloidpositive control subjects and patients with MCI or AD. Metabolism in parietal and precuneus cortices of AD patients was negatively correlated with PiB retention locally, and more distantly with PiB retention in frontal cortex. In amyloid-positive controls, no clear patterns in correlations were observed. In MCI patients, there were essentially no significant, negative correlations, but there were frequent significant positive correlations between metabolism and PiB retention. Metabolism in anterior cingulate showed positive correlations with PiB in most brain areas in MCI, and metabolism and PiB retention were positively correlated locally in precuneus/ parietal cortex. However, there was no significant increase in metabolism in MCI compared to age-matched controls, negating the possibility that A␤ deposition directly caused reactive hypermetabolism. This suggests that, in MCI, higher basal metabolism could either be exacerbating A␤ deposition or increasing the level of A␤ necessary for cognitive impairment sufficient for the clinical diagnosis of AD. Only after extensive A␤ deposition has been present for longer periods of time does A␤ become the driving force for decreased metabolism in clinical AD and, only in more vulnerable brain regions such as parietal and precuneus cortices.

Introduction There is a strong female preponderance reported in many connective tissue diseases and in almost all systemic sclerosis (SSc) case series. Methods We compared gender differences in SSc patients in a large single-center cohort, including demographic features, disease subtype, environmental exposures, disease-specific serum autoantibodies, organ system involvement (frequency and severity) and survival. Adjustment for cutaneous subset (diffuse cutaneous [dc] and limited cutaneous [lc]) was performed. Results We identified key characteristics which distinguished female from male SSc patients. Females were more frequently younger at disease onset with a longer disease duration at the time of their first visit. Females more often had lcSSc and, if an overlap syndrome was present, it was most often systemic lupus erythematosus. In contrast, males more frequently had dcSSc and overlap with myositis. Females more frequently had peripheral vascular involvement but in males it was more often severe. Males were more often cigarette smokers and more frequently had environmental exposures. Males more frequently had interstitial lung disease (ILD or pulmonary fibrosis) which was more severe. Females had a significantly increased frequency of anti-centromere antibody and males anti-topoisomerase I and anti-U3RNP antibody. Males had significantly reduced survival (73% at 5 years and 45% at 10 years after onset of SSc). The most frequent causes of death were ILD in males and pulmonary hypertension in females. Conclusions Gender differences may be important clues to understanding the natural history and pathogenesis of SSc.

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Objective This study examined amyloid-β (Aβ) deposition in 190 non-demented subjects aged 82 and older to determine the proportion of Aβ-positive scans and associations with cognition, APOE status, brain volume, and Ginko biloba (Gb) treatment. Methods Subjects who agreed to participate had a brain MRI and positron emission tomography scan with 11C-labeled Pittsburgh compound B (PiB) following completion of a Gb treatment clinical trial. The youngest subject in this imaging study was 82, and the mean age of the subjects was 85.5 at the time of the scans;152 (80%) were cognitively normal and 38 (20%) were diagnosed with mild cognitive impairment (MCI)at the time of the PiB study. Results A high proportion of the cognitively normal subjects (51%) and MCI subjects (68%) were PiB-positive. The APOE*4 allele was more prevalent in PiB-positive than in PiB-negative subjects (30% vs 6%). Measures of memory, language and attentional functions were worse in PiB-positive than in PiB-negative subjects, when both normal and MCI cases were analyzed together; however no significant associations were observed within either normal or MCI subject groups alone. There was no relationship between Gb treatment and Aβ deposition as determined by PiB. Interpretation The data revealed a 55% prevalence of PiB-positivity in non-demented subjects age >80 and 85% PiB-positivity in the APOE*4 non-demented elderly subjects. The findings also showed that long-term exposure to Gb did not affect the prevalence of cerebral Aβ deposition.

The standardized uptake value ratio (SUVR, or summed tissue ratio) has been used effectively in Pittsburgh compound B (PiB) PET studies to distinguish subjects who have significant amyloid-β deposition in their brain from those who do not. Relative to quantitative measurements, advantages of the SUVR are improved study feasibility and low test-retest variation; disadvantages include inherent bias (PiB retention overestimation) and potential for time-varying outcomes. The PiB SUVR has proven to be highly correlated with quantitative outcomes and to allow reliable detection of significant group differences (or effective contrasts). In this work, regional PiB SUVRs were examined across 9 time windows to select the window that provided the best trade-offs between bias, correlation, and effective contrast.Methods-A total of 40 dynamic PiB PET studies were performed on controls (n =16), patients with Alzheimer disease (AD; n =11), and patients with mild cognitive impairment (MCI; n = 13) (555 MBq [15 mCi], 90-min scan, and arterial blood sampling). The SUVR was computed for five 20-min and four 30-min windows that spanned the 30-to 90-min postinjection period. The SUVRs were compared with Logan graphical distribution volume ratio (DVR) measurements (35-90 min), determined with arterial blood as input and without arterial blood as input (cerebellum as reference).Results-Greater correlation and more bias were generally observed for the SUVR measurement at later times than at earlier times (relative to DVR). The effective contrast between the control and AD PiB SUVRs was slightly better for earlier data than for later data. The temporal dynamics of the SUVR measurement indicated greater stability in the measurement at 40 min after injection. Conclusion-The 50-to 70-min time window provided a good compromise between physiologic validity, stability, sensitivity, and clinical feasibility across the control, MCI, and AD subject data examined in this study. The 40-to 60-min period demonstrated many advantages and should be used in studies limited by low injected dose. Although more biased than the 40-to 60-min SUVR, the 50-to 70-min SUVR was thought to be optimal because of greater measurement stability, which may prove to be important for longitudinal multisite studies performed in control, MCI, and AD subjects that are not dose-limited.