O1‐01‐03: Relationship between regional amyloid levels and cognitive performance in healthy controls, MCI subjects, and patients with alzheimer's: Phase II results from a florpiramine F18 PET imaging study

Brain imaging in the study of Alzheimer's disease

“…They include [11C]-labeled “Pittsburgh Compound B (PIB),”(Klunk et al, 2004; Mathis et al, 2002) which has had a major impact on the field and other investigational ligands, including several [F18] ligands that are being developed for the clinical setting due to their longer radioactive half-life and the ability to transport the tracer to different PET Centers from a regional radiopharmacy (Choi et al, 2009; Jureus et al, 2010; Nelissen et al, 2009; Rowe et al, 2008; Tolboom et al, 2009; Vandenberghe et al, 2010). Among other things, fibrillar Aβ PET studies have already confirmed the cortical distribution of fibrillar Aβ in clinically affected patients, with preferential deposition in precuneus, posterior cingulate, parietotemporal, and frontal regions and relative sparing in the hippocampus, and they have suggested that fibrillar Aβ levels are virtually saturated by the time patients have MCI (Doraiswamy et al, 2009; Forsberg et al, 2008; Grimmer et al, 2009; Jack, Jr. et al, 2008; Kemppainen et al, 2007; Klunk et al, 2004; Klunk et al, 2006; Morris et al, 2009; Resnick et al, 2010; Rowe et al, 2007; Rowe et al, 2010; Villemagne et al, 2011; Wolk et al, 2009) (Figure 3). They have suggested significant fibrillar Aβ deposition in about 30% of cognitively normal adults over the age of 70, perhaps 10-15 years before clinical onset, and that the magnitude and spatial extent of fibrillar Aβ is associated with older age and the genetic risk for late-onset AD (Aizenstein et al, 2008; Mintun et al, 2006; Morris et al, 2010; Pike et al, 2007; Reiman et al, 2009; Rowe et al, 2010; Small et al, 2009; Villemagne et al, 2011).…”

Twelve-month metabolic declines in probable Alzheimer's disease and amnestic mild cognitive impairment assessed using an empirically pre-defined statistical region-of-interest: Findings from the Alzheimer's Disease Neuroimaging Initiative

“…For these and other reasons, researchers have sought to develop biomarker endpoints that reflect AD progression or pathology and that could help to assess putative AD-slowing treatments with better statistical power than clinical endpoints (Jones et al, in press; Landau et al, in press). To date, the best established biomarkers of AD progression are volumetric magnetic resonance imaging (MRI) measurements of brain shrinkage (Fox et al, 1999; Fox et al, 2000; Hua et al, 2009; Jack, Jr. et al, 2008; Schuff et al, 2009) and fluorodeoxyglucose positron emission tomography (FDG PET) measurements of regional cerebral metabolic rate for glucose (CMRgl) decline (Alexander et al, 2002; Reiman and Langbaum, 2009; Reiman et al, 2001) and the best established biomarkers of AD pathology are fibrillar amyloid-β (Aβ) PET measurements using Pittsburgh Compound B (PiB) and other recently developed radioligands (Doraiswamy et al, 2009; Jack, Jr. et al, 2009; Johnson et al, 2009; Klunk et al, 2004; Nyberg et al, in press; Shoghi-Jadid et al, 2002; Small et al, 2006) and cerebrospinal fluid (CSF) Aβ, total tau and phospho-tau levels (Fagan et al, 2006; Fagan et al, 2007; Fagan et al, 2009; Hansson et al, 2006; Hansson et al, 2009; Li et al, 2007; Sunderland et al, 2004). …”