DIAGNOSTIC CRITERIA FOR EARLY ALZHEIMER’S DISEASE

The diagnosis of MCI, particularly the amnestic subtype, has often been used to identify patients
78 in the early stages of AD, although not all patients with this diagnosis progress to develop
79 dementia. In recent years, the research community has actively sought to develop improved
80 diagnostic guidelines for the accurate identification of these patients, primarily through the
81 incorporation of various biomarker-based criteria into their framework (i.e., to add anatomic
82 evidence to the somewhat uncertain characterization of MCI). Leading examples of such efforts
83 are the research criteria for prodromal AD, published by the International Working Group for
84 New Research Criteria for the Diagnosis of AD (Dubois, Feldman, et al. 2010), and MCI due to
85 AD by a National Institute on Aging — Alzheimer’s Association working group (Albert,
86 DeKosky, et al. 2011).
87
88 Research diagnoses such as preclinical AD have also been developed by these same groups in an
89 attempt to identify patients even earlier in the disease continuum who are considered at-risk for
90 developing AD dementia because of the presence of certain AD biological hallmarks. Although
91 these criteria rely primarily on the presence of biomarker changes, they also allow for the use of
92 sensitive (albeit yet undeveloped) clinical measures to detect subtle evidence of cognitive
93 decline.
94
95 We acknowledge that many similarities exist between the leading diagnostic guideline proposals
96 for the earliest stages of AD, and we support the concept of enriching trial populations with
97 patients most likely to progress to more overt dementia, using both clinical and biomarker-based
98 criteria. However, the need for an assessment of sensitivity and specificity in identifying patients
99 who do have actual AD in clinical trials, as well as for the validation of the respective component
100 methodologies (e.g., the selection of appropriate cut-points, assessment of assay variability),
101 does not allow the FDA to formally endorse any specific diagnostic frameworks at this time.