The prognostic value of amyloid imaging.
ABSTRACT Mild cognitive impairment is characterized by a decline in cognitive performance without interference with activities of daily living. The amnestic subtype of mild cognitive impairment progresses to Alzheimer's disease at a rate of 10-15% per year and in the majority the neuropathology is intermediate between the neuropathological changes of typical ageing and Alzheimer's disease. Amyloid deposition occurs over a decade before the development of noticeable cognitive symptoms in a continuous process that starts in healthy elderly individuals. Newly developed PET amyloid imaging agents provide noninvasive biomarkers for the early in vivo detection of Alzheimer's pathology in healthy elderly individuals and those with mild cognitive impairment. Exclusion of amyloid pathology should allow a more accurate prognosis to be given and ensure appropriate recruitment into clinical trials testing the efficacy of new putative antiamyloid agents at an earlier disease stage. The development of (18)F-labelled amyloid imaging agents has increased the availability of this new technology for clinical and research use since they can be used in PET centres where a cyclotron and radiochemistry are not available. This review discusses the role of PET imaging for assessing the amyloid load in cognitively normal elderly subjects and subjects with mild cognitive impairment at risk of conversion to Alzheimer's disease.
- SourceAvailable from: Urszula Wojda[Show abstract] [Hide abstract]
ABSTRACT: Major breakthroughs are required to win the war against the increasing threat of Alzheimer's disease. Until now, however, despite enormous efforts and funds, effective therapies are lacking, and adequate models for drug validation are still unavailable. In this article, we review the available animal and cellular models of different features of human Alzheimer's disease and critically evaluate their usefulness for understanding the mechanisms of the disease. The majority of the presently used models are based on the amyloid-β and hyperphosphorylated tau hypothesis, which resembles features of familial Alzheimer's disease. Unfortunately, these models offer limited help for understanding the pathomechanisms of the early stages of sporadic Alzheimer's disease. Thus, new models are needed to discover ways to treat or delay the onset of Alzheimer's disease, and we discuss the prospects for such desperately needed models, including human induced pluripotent stem cells and in silico brain models.Journal of Alzheimer's disease: JAD 01/2013; 34(3). DOI:10.3233/JAD-121984 · 3.61 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: We conducted a meta-analysis of relationships between amyloid burden and cognition in cognitively normal, older adult humans. Methods of assessing amyloid burden included were CSF or plasma assays, histopathology, and PET ligands. Cognitive domains examined were episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Sixty-four studies representing 7,140 subjects met selection criteria, with 3,495 subjects from 34 studies representing independent cohorts. Weighted effect sizes were obtained for each study. Primary analyses were conducted limiting to independent cohort studies using only the most common assessment method (Pittsburgh compound B). Exploratory analyses included all assessment methods. Episodic memory (r = 0.12) had a significant relationship to amyloid burden. Executive function and global cognition did not have significant relationships to amyloid in the primary analysis of Pittsburgh compound B (r = 0.05 and r = 0.08, respectively), but did when including all assessment methods (r = 0.08 and r = 0.09, respectively). The domains of working memory, processing speed, visuospatial function, and semantic memory did not have significant relationships to amyloid. Differences in the method of amyloid assessment, study design (longitudinal vs cross-sectional), or inclusion of control variables (age, etc.) had little influence. Based on this meta-analytic survey of the literature, increased amyloid burden has small but nontrivial associations with specific domains of cognitive performance in individuals who are currently cognitively normal. These associations may be useful for identifying preclinical Alzheimer disease or developing clinical outcome measures.Neurology 04/2013; 80(14):1341-8. DOI:10.1212/WNL.0b013e31828ab35d · 8.30 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The potential of brain imaging has grown rapidly with new modalities, hybrid combinations of existing modalities, and novel metabolic tracers. F-florbetapir is an amyloid plaque-binding molecule labeled to F that allows positron imaging of the amyloid deposition in the brain. This protein deposition is known to be one of the features in Alzheimer disease and therefore can be of interest in the differential diagnosis of dementia. We present 2 cases combining the new hybrid imaging modality PET/MRI, which offers molecular and morphological information, with F-florbetapir in the differential diagnosis of dementia.Clinical nuclear medicine 07/2013; 36(6). DOI:10.1097/RLU.0b013e31829b9e5f · 2.86 Impact Factor