Cognition, glucose metabolism and amyloid burden in Alzheimer's disease

Abstract

We investigated relationships between glucose metabolism, amyloid load and measures of cognitive and functional impairment in Alzheimer’s disease (AD). Patients meeting criteria for probable AD underwent [11C]PIB and [18F]FDG PET imaging and were assessed on a set of clinical measures. PIB Distribution volume ratios and FDG scans were spatially normalized and average PIB counts from regions-of-interest (ROI) were used to compute a measure of global PIB uptake. Separate voxel-wise regressions explored local and global relationships between metabolism, amyloid burden and clinical measures. Regressions reflected cognitive domains assessed by individual measures, with visuospatial tests associated with more posterior metabolism, and language tests associated with metabolism in the left hemisphere. Correlating regional FDG uptake with these measures confirmed these findings. In contrast, no correlations were found between either voxel-wise or regional PIB uptake and any of the clinical measures. Finally, there were no associations between regional PIB and FDG uptake. We conclude that regional and global amyloid burden does not correlate with clinical status or glucose metabolism in AD.

Diagnostic utility of ASL‐MRI and FDG‐PET in the behavioral variant of FTD and AD

“…Tracer synthesis, PET acquisition, and preprocessing were performed as previously described 39. Thirty minutes of dynamic FDG data ( t = 30–60 min postinjection) were obtained.…”

Brain Imaging in Alzheimer Disease

“…Several groups have observed high amyloid deposition in parietal regions to be associated with co-localized FDG hypometabolism, possibly indicating a local toxicity (Klunk et al 2004;Engler et al 2006;Edison et al 2007;Cohen et al 2009). In other groups, this association was not statistically significant, possibly because the amyloid burden in these patients was already at its plateau (Kadir et al 2008;Furst et al 2010). An important clue to this relationship could lie in the observation that the relation is consistently weaker in frontal regions, where some of the highest amyloid burdens are found (Klunk et al 2004;Edison et al 2007).…”

“…Differences in FDG between MCI and normal aging have not typically been large, but the control groups in most of these studies were likely contaminated with a number of individuals who, although clinically normal, were amyloid positive (see below) and possibly in earlier phases of preclinical AD. FDG hypometabolism parallels cognitive function along the trajectory of normal, preclinical, prodromal, and established AD (Minoshima et al 1997;Furst et al 2010); however, higher levels of brain and cognitive reserve are well known to attenuate the strength of these correlations and highly intelligent AD patients can be clinically mild, but severely hypometabolic (Stern et al 1992;Alexander et al 1997). Coexisting vascular disorders, including ischemia, amyloid angiopathy, and micro-hemorrhage, potentially confound the relation of FDG to clinical phenotype, but the classic AD FDG pattern is well correlated with histopathologic diagnosis of AD at autopsy (Hoffman et al 2000;Jagust et al 2007).…”

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

“…Although significant correlations between memory performance and Ab load have been detected in some cohorts of nondemented individuals (8,(11)(12)(13)(14)(15), they could not be found in others (9,13,14,(16)(17)(18)(19). When such correlations within groups of AD patients were evaluated, most studies did not find significant results (7,9,15,16,(20)(21)(22). This may in part be explained by the fact that the rate of cerebral Ab accumulation is apparently highest before the onset of dementia and decreases in symptomatic AD stages (1), resulting in little variability of amyloid burden within the groups of AD patients despite variable degrees of cognitive impairment.…”

“…This may in part be explained by the fact that the rate of cerebral Ab accumulation is apparently highest before the onset of dementia and decreases in symptomatic AD stages (1), resulting in little variability of amyloid burden within the groups of AD patients despite variable degrees of cognitive impairment. Only a few studies thus far have investigated amyloid deposition, glucose metabolism, and memory in the same patient (4,5,16,20,21,23) and yielded inconclusive results. Although memory deficits were typically related to hypometabolism, Ab load and glucose metabolism were found to be negatively correlated-predominantly in parietal, frontal, and posterior cingulate or precuneus cortex-in most (4,5,16,20,23), but not all, studies (21).…”