Positron emission tomography (PET) has been used to study Alzheimer’s disease (AD) as well as various stages of age-related cognitive decline. Studies of cerebral glucose metabolism using [18F]fluorodeoxyglucose (FDG) have demonstrated that regional metabolic patterns vary among different forms of degenerative dementia and that these patterns can predict clinical progression and definitive diagnosis with high degrees of accuracy. When FDG-PET scan measures are combined with apolipoprotein E-4 (APOE-4) measures of AD genetic risk, parietal, temporal, and posterior cingulate deficits are observed in middle-aged people and older adults at genetic risk. At follow-up, metabolic decline consistently continues in at-risk individuals and patients with AD.
Such results have led to current clinical trials of medications and non-pharmacological strategies using PET as a surrogate marker. Initial studies of cholinesterase inhibitor drugs show that cerebral metabolic rates and cognitive measures stabilize or improve after treatment. More recently, PET scans have provided signals measuring cerebral amyloid neuritic plaques and neurofibrillary tangles, and such signals correlate with cognitive scores in AD patients and even in non-demented controls. These kinds of approaches offer promise for PET as a useful surrogate marker for drug discovery in AD and age-related cognitive decline. Several lines of evidence suggest that environmental factors and lifestyle choices influence the rate of brain aging and the risk of AD, and PET surrogate markers may also effectively monitor such non-pharmacological interventions. This review will consider these discoveries and their implications for current and future studies of medications and non-pharmacological approaches for both treatment and prevention of AD.
Back to S019 New Drug Development in Psychogeriatrics
Back to The Eleventh International Congress