Finally, CN individuals who are A??-negative and do not the show accelerated longitudinal decline in memory can be reassured that they are not likely to develop AD over the next several years. CN individuals who are A??-positive and have stable longitudinal memory performance may represent the group of asymptomatic AD or may not have reached a threshold of pathology where memory decline is evident. These findings, of course, must be interpreted in the context of an individual’s age and APOE genotype, as younger CN individuals with A?? pathology may not have passed through the risk period for accelerated cognitive decline and dementia. Longitudinal follow-up studies will determine the time course of the development of A?? and whether there truly are individuals who are resilient to pathology or in whom the clinical symptoms are delayed.

Moreover, comparisons between A??-positive individuals who have stable memory performance and those who show cognitive decline and impairment may lead to identification of factors that promote cognitive resilience despite pathology. The ability to stratify longitudinal trajectories of memory performance by A?? will also inform and perhaps revise our definition of what constitutes ‘normal aging’ in the absence of pathology. Finally, prediction models incorporating other factors, such as APOE genotype, cerebrospinal fluid (CSF) A?? and Tau, as well as both regional and network-based spatial measures of brain atrophy on MRI [47] may increase sensitivity and specificity GSK-3 for early identification of AD and cognitive resilience.

Table Axitinib cancer 4 Joint consideration of ??-amyloid and cognition for prediction of cognitive outcomes In addition to its contributing role in early identification of individuals at greatest risk for AD, amyloid imaging is also aiding in drug development and elucidating the regional distribution and temporal course of the neuro-biological changes leading to memory loss and AD. Amyloid imaging informs the selection of participants in therapeutic trials – for example, for anti-A?? treatments – and may be useful in monitoring therapeutic response. In one recent trial, an 8.5% decline in A?? level was detected in response to an anti-A?? treatment [48]. PET amyloid imaging is also being used in combination with CSF and MRI measures to track the temporal course and regional brain changes preceding memory loss. Amyloid deposition is hypothesized to be an early stage of the disease process, with functional and structural brain changes, including hippocampal volume loss, occurring closer to the manifestation of clinical symptoms [49]. Imaging tools provide information throughout the brain, directing attention to the regions showing the earliest amyloid deposition and volumetric changes.