P2‐215: Supporting evidence of the Alzheimer's disease biomarker dynamic model in patients with mild cognitive impairment

A pathophysiologic model of Alzheimer's disease (AD) has been recently proposed in which beta amyloid accumulation occurs earlier (indexed by abnormal CSF Abeta42), followed by tau-mediated neuronal injury and dysfunction (abnormal CSF tau or FDG-PET) and lastly atrophic changes (abnormal hippocampal volume, HV). The aim of this study is to validate this model by comparing clinical features and conversion to AD and other dementias among groups of patients with mild cognitive impairment (MCI) with different abnormal biomarker profiles. The patients of this study were 58 with MCI in whom AD biomarkers (CSF Abeta42 and tau, temporoparietal hypometabolism on 18F-FDG PET, and hippocampal volume) were collected. Patients were divided into 3 groups of no abnormal biomarker, AD biomarker pattern (including 3 subgroups of early = only abnormal Abeta42, intermediate = abnormal Abeta42 and FDG-PET or tau, and late = abnormal Abeta42, FDG-PET or tau, and HV), and any other biomarker combination. MCI patients with AD biomarker pattern had lower behavioral disturbances than patients with any other biomarker combination (P <.0005) and lower performance on verbal and nonverbal memory than the other two groups (P = .07 and P = .004, respectively). Within the 3 subgroups with AD biomarker pattern there was a significant trend to higher rate of conversion to dementia (p for trend = .006). Moreover, AD was the type of incident dementia in 100% of patients with an AD biomarker pattern, but 0% and 27% in converters with no abnormal biomarker and any other biomarker combination, respectively (P = .002). Clinical cases representative of the three groups were also described. The results of this study provide evidence in favor of the dynamic biomarker model and support the use of biomarkers for the diagnosis of MCI due to AD according to the new recently published research criteria.