P1-198: Biology-based approach to mild cognitive impairment

Abstract

Mild cognitive impairment (MCI) is interpreted to be pre- Alzheimer disease (AD). However, our neuropathological studies of an aged cohort did not support the hypothesis. Consecutive autopsy cases from an aged cohort were immunohistochemically examined for the correlation between cognitive state and neuropathological findings. Based on these findings, screening of MCI was done with surrogate biomarkers including objective psychological tests, cerebrospinal fluid biomarker (tau, phosphorylated tau and Abeta 1–42), voxel based morphometry of three dimentionally acquired MRI and specific volumetric analysis of brain perfusion SPECT and results were confirmed by FDG (11F deoxy glucos) and PIB (Pittsburgh Compound B) PET scans. For pathological study, retrospectively determined CDR 0.5 was interpreted to be equivalent for MCI. Neuropathology of MCI consisted of large number of senile tuopathy (argyrophlic grain dementia and neurofibrillary tangle- predominant form of dementia) as well as AD, dementia with Lewy bodies (DLB) and vascular disorders. Among 40% cases who were classified into dementia (CDR>=1), AD pathology can only explain 1/4. For longitudinal clinical studies, MCI is operatively defined as MMSE>=24 and Rivermead Behavioral Memory Test Standard Profile Test <16. MCI was classified into presymptomatic AD, when both CSF biomarkers and neuroimages (either MRI or SPECT) were consistent with AD. Among those cases who were classified into AD- MCI, twenty percent of cases are negative for PIB PET scans. FDG of theses cases showed severe metabolic fall in mesial temporal lobe. Both clinical and pathological studies strongly suggest that MCI contained various pathological backgrounds, in addition to AD. In Japan, FDG and PIB are not reimbursed by medical insurance, but these sets are apparently essential for accurate diagnosis of MCI. Pathological correlation between FDG and PIB PET scan are now on going.