Positron Emission Tomography of Amyloid in Alzheimer's Disease

Alzheimer's disease (AD) is a fatal neurodegenerative disorder characterized by progressive impairment in daily life, cognitive deterioration, and a variety of neuropsychiatric and behavioural symptoms. The diagnosis of AD is based on clinical criteria, but these have low sensitivity and specificity for AD in the early stages of the disease. Therefore, there is a great need for a method to identify the pathological process of AD at an earlier, preclinical stage. In-vivo imaging and quantification of pathological beta-amyloid (Aß) accumulation may provide such a method as the production and accumulation of Aß is thought to be central to the pathogenesis of AD. The view is widely held that Aß may be present in the brain at sublethal concentrations for extended periods before the overt manifestation of AD. Therefore, early, in-vivo detection of pathological Aß accumulation is warranted and may identify subjects at risk for AD. Neuroimaging with Positron Emission Tomography (PET) permits in-vivo imaging and quantification of cerebral amyloid load, which is a novel application of PET. Recently, several PET tracers ([18F]FDDNP and [11C]PIB) have been developed for this purpose and the first clinical studies in patients with AD are encouraging. For both tracers, many methodological issues still need to be resolved and the clinical value of in-vivo amyloid imaging remains to be established. The most important objectives of this project are twofold: to provide an independent and unbiased evaluation of the value of in-vivo amyloid imaging in the (early) diagnosis of AD and to optimize methods for quantification of the in-vivo cerebral amyloid load. To investigate the value in the early diagnosis, identification of subjects at risk for AD is essential. Patients with amnestic mild cognitive impairment (MCI), i.e patients suffering only from memory problems but without the other symptoms of AD, are recruited for this purpose. MCI is a disease state considered to be a transitional state between normal aging and dementia. It is generally accepted that the ability to identify the presence of Alzheimer type pathology in the MCI stage will benefit disease management. Twenty patients with amnestic MCI, 15 patients with AD and 15 age and sex matched healthy controls will be included in this study. Only consecutive new patients fulfilling criteria of amnestic MCI will be included. Patients with MCI will remain under clinical observation during two years after participation in order to monitor conversion to clinical dementia. All subjects will receive [11C]PIB and [18F]FDDNP PET scans on a single day. In addition, patients will receive a [18F]FDG PET scan. Furthermore, an MRI scan, a neuropsychological evaluation and CSF analysis for diagnostic purposes will be performed in all subjects.