Dementia; Early Diagnosis; Positron emission tomography; Beta-Amyloid Imaging; PET; PIB; Alzheimer's disease
Steininger Stefanie C, Liu Xinyang, Gietl Anton, Wyss Michael, Schreiner Simon, Gruber Esmeralda, Treyer Valerie, Kälin Andrea, Leh Sandra, Buck Alfred, Nitsch Roger M, Prüssmann Klaas P, Hock Christoph, Unschuld Paul G (2014), Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System., in Frontiers in aging neuroscience
, 6, 52-52.
Kälin Andrea M, Pflüger Marlon, Gietl Anton F, Riese Florian, Jäncke Lutz, Nitsch Roger M, Hock Christoph (2014), Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer's disease., in Frontiers in aging neuroscience
, 6, 147-147.
Riese Florian, Gietl Anton, Zölch Niklaus, Henning Anke, O'Gorman Ruth, Kälin Andrea M, Leh Sandra E, Buck Alfred, Warnock Geoffrey, Edden Richard A E, Luechinger Roger, Hock Christoph, Kollias Spyros, Michels Lars (2014), Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype., in Neurobiology of aging
Schreiner Simon J, Liu Xinyang, Gietl Anton F, Wyss Michael, Steininger Stefanie C, Gruber Esmeralda, Treyer Valerie, Meier Irene B, Kälin Andrea M, Leh Sandra E, Buck Alfred, Nitsch Roger M, Pruessmann Klaas P, Hock Christoph, Unschuld Paul G (2014), Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects., in Frontiers in aging neuroscience
, 6, 240-240.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease with a considerable increase in incidence in the aging population. Beta-amyloid pathology is a central feature of the neuropathology in AD, with the build-up and accumulation of beta-amyloid commencing as early as 30 years before the onset of initial clinical signs of dementia, as suggested by neuropathological studies. Pittsburgh Compound B (PIB) PET-imaging can reiably detect brain beta-amyloidosis in living subjects. Because of the known conversion of PIB-positive subjects with mild cognitive impairment to clinically manifest AD, the presence of PIB-positive brain beta-amyloidosis can be considered a major risk factor for the development of dementia. Human brain aging occurs both with and without the development of progressive brain beta-amyloidosis, and it is hypothesized that the development of progressive beta-amyloidosis is a preclinical, prodromal state of Alzheimer’s disease that will eventually become clinically manifest. The factors, however, contributing to progressive brain beta-amyloidosis occurring during normal aging are unknown. This research program is designed to compare PIB-positive healthy elderly subjects with brain beta-amyloidosis to matched PIB-negative elderly subjects without brain beta-amyloidosis and to determine whether cognitive, genetic (ApoE4), cardiovascular (lipids, cholesterol, blood pressure, obesity), prior episodes of brain disease (ischemia, trauma, depression) and structural (brain atrophy) factors correlate with PIB-positive PET scans. In a further planned study, we plan to re-mage study participants with PIB-PET three years following the initial scan in order to determine that rates of progression of brain beta-amyloidosis over time.The program will test the following Working Hypotheses: (1) that brain beta-amyloidosis is occurring more frequently in ApoE4-positive subjects as well as in subjects with cardiovas-cular risk factors or brain trauma, (2) that brain beta-amyloid is associated with initial signs of compromised cognitive functions compatible with mild cognitive impairment (MCI), and (3) that brain beta-amyloidosis is associated with initial signs of brain atrophy.The Specific Aims of this project are:1.To characterize differences is cognitive functions in healthy elderly subjects with and without brain beta-amyloidosis.2.To determine whether ApoE genotype or cardiovascular risk factors are associated with brain beta-amyloidosis in healthy elderly subjects.3.To determine the effects of prior episodes of such brain diseases as ischemia, depression or trauma are associated with brain beta-amyloidosis.4.To determine whether brain-beta amyloidosis is associated with MRI signs of brain atrophy. Experimental Design and Methods - To achieve these aims, we will recruit 100 healthy elderly subjects aged 55 to 70 with subjective memory complaints but with no clinical signs of dementia. In collaboration with the Department of Nuclear Medicine (Profs. Gustav von Schulthess and Freddi Buck) we will perform PET-Imaging of PIB radiochemically synthesized under GMP condition in collaboration with Prof. P. August Schubiger at the Center for Radiopharmaceutical Science of ETH, PSI and USZ. Initial signs of progressively compromised cognition will be determined both upon inclusion and 18 months later by standardized neuropsychological test batteries normalized for the healthy elderly population. Cardiovascular risk factors will be analyzed in collaboration with Prof. Thomas Lüscher by using a standardized battery of blood tests, clinical examinations and anam-nestic investigations. The history of prior brain diseases will be validated though patient record files, and signs of progressive brain atrophy will be determined by using MRI brain volumetry with a period of 18 months. Expected value - The results generated by these studies will identify factors that influence the development of brain beta-amyloidosis in healthy elderly subjects. Should it turn out that brain beta-amyloidosis is associated with signs of compromised cognition or signs of brain atrophy, this population of elderly subjects could become a prime target population for primary prevention of Alzheimer’s disease by using beta-amyloid-reducing therapy.