Understanding early events in Alzheimer disease (AD) pathogenesis: Integration of molecular, functional and structural imaging

This project will develop and employ integrated imaging techniques in the longitudinal study of patients with mild cognitive impairment (MCI). We aim to study mechanisms for Alzheimer disease induction, and to determine factors predictive for cognitive de cline and conversion to dementia. Fractional anisotropy , white matter lesions (WML), tractograms and functional imaging (FDG-PET) will be related to brain morphometry measures, to see if these factors may predict cortical volume loss in MCI patients. A special focus is to relate earlier findings concerning ischemic white matter lesions and CSF biomarker pathology (i.e. low CSF Ab42) to white matter tractograms and amyloid depositions as visualized by PIB amyloid imaging, to examine a putative causal rel ationship between WML and amyloid deposition. The ongoing multi-senter study (GO-MCI) is tailored to answer these research questions, encompassing patients with subjective memory deficits only, as well as ordinary MCI patients with detectable cognitive l oss and a control group (spouses). Building up special expertise and methods/tools that early confirms and predict the course of AD is important to improve diagnosis and hopefully treatment within this patient group. The project contributes to networks f or research in establishing ties between clinical centers, centers for advanced neuropsychology and imaging and for advanced proteomics. This research concerns major patient groups where we at present lack insight in the fundamental mechanisms of disease, and also lack established treatment that may alter the course of the diseases. The disease is detrimental to life quality and health of both patients and caregivers, and among the most costly diseases especially at advanced stages. Demographic and epidem iological trends indicate major increases in disease prevalence in the near future, making progress in research and disease-modifying treatment pressing.