Subthreshold Increases in Beta-Amyloid Correlate with Memory Decline in Healthy Adults

Friday, March 23, 2018


Susan M. Landau, Andy Horng, and William J. Jagust for the Alzheimer's Disease Neuroimaging Initiative published findings (Neurology. 2018:published online March 23, 2018) that show amyloid increases within the negative range are associated with poorer longitudinal memory performance. Previous studies have shown that extensive Aβ levels in the brain are linked to cognitive decline and these studies have been used to set a threshold level for Aβ positive status. This study now shows that accumulating Aβ  

Investigators used [18F]-florbetapir-PET scanning to examine subjects β-amyloid (Aβ) levels in the brain. Florbetapir binds to amyloid and signal intensity of the bound tracer can be used to quantify Aβ accumulation. Longitudinal memory performance and executive function with also assessed in the study participants.

The study subjects included 142 cognitively normal older individuals who were Aβ-negative at baseline and had at least 2 [18F]-florbetapir PET scans during a period of 3.9 ± 1.4 years. The increase in Aβ accumulation among those who were baseline-negative for Aβ was not related to baseline memory or executive function, hippocampal volume, temporoparietal lobe glucose metabolism, APOE4 status, age, sex, or education of the individuals, and the mean annual increase was 0.002 ± 0.008 standardized uptake value ratio units per year. Accumulation of Aβ was related to higher level of Aβ at baseline, suggesting that accumulation had already begun in those for whom it was seen throughout the study.

During follow-up, 13 individuals converted to Aβ positive status, and 14 individuals converted to a diagnosis of mild cognitive impairment (MCI); however, there was little overlap amongst individuals in those two groups. Amyloid accumulation among all baseline-negative individuals did not correlate with changes in executive function but did correlate with declining memory performance (P = 0.019). In individuals who had at least 3 [18F]-florbetapir-PET scans with in the period of the study, the correlation between Aβ accumulation and memory decline was stronger (P=.007).  

The authors concluded that subthreshold increases in Aβ may represent the earliest dectectable indication of illness that has domain-specific effects on cognition. These findings are important in the search for disease-modifying treatments as they suggest earlier identification of individuals who are accumulating Aβ, perhaps even at subthreshold levels, may lead to more successful clinical trials. 

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