One recent preliminary report [59] was consistent with the results above showing a relationship between florbetapir order inhibitor PET amyloid binding and prospectively measured cognitive decline. In summary, the data to date are limited, but taken together provide evidence that abnormal accumulation of A?? as evidenced by PET amyloid imaging is associated with increased risk of both concurrent cognitive deficits and subsequent progression of cognitive impairment, and thus may be pathological even in apparently cognitively normal subjects. Conclusion Emerging consensus regarding diagnostic algorithms and criteria suggests that diagnosis of AD can be enhanced by use of biomarkers to increase certainty, and, in early stages, to identify the group of patients at risk for progression to AD.

The data reviewed above suggest that PET amyloid imaging may be well suited to both tasks. Amyloid binding on PET has been shown to be strongly correlated with brain A?? burden at autopsy, and PET imaging identified amyloid-positive subjects with a high sensitivity and specificity in relationship to postmortem histopathological criteria for AD. Additionally, there is consistent evidence that PET imaging can identify subjects with elevated A?? burden, even at early stages of disease, and preliminary evidence suggests that excess A?? accumulation, as evidenced by PET imaging, has implications for both present and future cognitive performance. Current theory suggests that A?? accumulation may be a critical early step in a cascade of events, including phosphoryl tau and inflammation-mediated synaptic damage and neuronal loss, that leads to cognitive impairment in AD.

Early identification of subjects with A?? accumulation may be critical to the development of potential disease-modifying therapies because amyloid targeted therapies may not be effective once later stages of the cascade have begun. There is an opportunity to identify patients earlier than occurs in current clinical practice. Typical patients in clinical trials, who are generally well educated and well integrated into the medical system, report delays of approximately 2 years between symptom onset and diagnosis. Delays may be even greater in a community setting where physicians are known to overlook diagnoses in a substantial proportion of patients. However, improved diagnostic aids, such as amyloid-targeted PET scans, alone may not be sufficient to overcome this problem.

Diagnostic delays may be partly a matter AV-951 of patient education (recognition and acceptance of AD symptoms, readiness to seek treatment) and physician practice. In particular, some physicians may be unwilling to commit to diagnosis in the absence of viable treatments. On the other hand, tools that provide evidence of the underlying during pathology might improve physician’s confidence, and lead to an earlier diagnosis, by reducing the need for longitudinal follow-up and progression to a more advanced stage of symptoms.