Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease

Abstract

Recent developments of PET amyloid ligands have made it possible to visualize the presence of Aβ deposition in the brain of living participants and to assess the consequences especially in individuals with no objective sign of cognitive deficits. The present review will focus on amyloid imaging in cognitively normal elderly, asymptomatic at-risk populations, and individuals with subjective cognitive decline. It will cover the prevalence of amyloid-positive cases amongst cognitively normal elderly, the influence of risk factors for AD, the relationships to cognition, atrophy and prognosis, longitudinal amyloid imaging and ethical aspects related to amyloid imaging in cognitively normal individuals. Almost ten years of research have led to a few consensual and relatively consistent findings: some cognitively normal elderly have Aβ deposition in their brain, the prevalence of amyloid-positive cases increases in at-risk populations, the prognosis for these individuals is worse than for those with no Aβ deposition, and significant increase in Aβ deposition over time is detectable in cognitively normal elderly. More inconsistent findings are still under debate; these include the relationship between Aβ deposition and cognition and brain volume, the sequence and cause-to-effect relations between the different AD biomarkers, and the individual outcome associated with an amyloid positive versus negative scan. Preclinical amyloid imaging also raises important ethical issues. While amyloid imaging is definitely useful to understand the role of Aβ in early stages, to define at-risk populations for research or for clinical trial, and to assess the effects of anti-amyloid treatments, we are not ready yet to translate research results into clinical practice and policy. More researches are needed to determine which information to disclose from an individual amyloid imaging scan, the way of disclosing such information and the impact on individuals and on society.

Ic‐p‐118: Amyloid Burden, Cortical Thickness, and Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention

“…Similar to our colocalized PiB/MRI analyses, although only the parahippocampal gyrus neared statistical significance in our analysis of the potential Ab-induced acceleration of agerelated cortical thinning, there was a general tendency for increased Ab to be associated with faster age-related cortical thinning across the other ROIs examined. This supports the notion that even ostensibly mild Ab aggregation might not be innocuous, perhaps becoming more pernicious with the passage of time [47].…”

“…A meta-analysis of studies investigating Ab-cognition effects in CN individuals [49] suggested that although there is a modest association between amyloid accumulation and cognition, effect sizes in areas other than episodic memory and global cognition are small. Chetelat and colleagues [47] suggested that the variations in the observed effect of Ab on cognition may be due to differences in the underlying characteristics of the study samples, especially in age and APOE ε4 status. In the present study, we found that, despite the apparent Ab-induced degeneration of the entorhinal cortex and amygdala-two structures critical to episodic memory-there were no statistically significant main effect of Ab on memory or other cognitive functions, although the Ab1 group consistently exhibited lower cognitive test scores than the Ab2 group.…”

“…Second, we determined cerebral amyloidosis via qualitative ratings. Although this approach has potential clinical value (patients are likely to be more interested in whether their PiB scans are indicative of AD versus whether their PiB binding is 1.2) and has established precedence in the literature (for an excellent review, see Chetelat et al [47]), there is a possibility that we might have made different observations had we used a quantitative approach such as by averaging PiB uptake in select ROIs. Similarly, although our use of an ROI approach to investigate the effect of Ab burden on brain structure made our enquiry focused and hypothesis driven, it may have resulted in a failure to detect findings that were outside the examined ROIs.…”

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

“…Given the biphasic distribution in the HAMCs (Figure 1), using a more conservative wcDVR cutoff such as 1.5 35 would further strengthen, rather than weaken, this observation, since using this cutoff would result in 3/9 HAMCs versus 2/11 CAA patients being PiB þ . As reviewed recently, 18,36 20% to 40% of healthy elderly 460 years of age (and up to 50% above 80) have a significant amyloid burden on PET imaging, despite normal general cognition. 37 Our prevalence of 44% is therefore high but consistent with these ranges.…”

Advances in the therapy of Alzheimer’s disease: targeting amyloid beta and tau and perspectives for the future

“…Moreover, some patients with 'typical' signs and symptoms of AD show negative scans. So for the time being a positive amyloid scan must be considered in the full clinical picture of a patient, on the other hand, a negative amyloid scan indicates that the likelihood of cognitive impairment due to AD might be low, nevertheless, further data on sensitivity and specificity are needed [135][136][137][138].…”