[In vivo imaging for evaluating synaptic integrity in Alzheimer disease]

In vivo imaging of regional brain glucose metabolism or blood flow (which is coupled to glucose metabolism) can elucidate regional brain synaptic activity, which is supported by mitochondrial oxidative phosphorylation. In Alzheimer disease, postmortem evidence indicates that synaptic loss correlates with dementia severity, and that oxidative phosphorylation in individual neurons declines in relation to the severity of synaptic dysfunction and the intracellular accumulation of neurofibrillary tangles. Brain imaging in asymptomatic and diagnosed Alzheimer disease patients confirms and extends this scenario. Resting state brain glucose metabolism falls with dementia severity, particularly in brain association areas. However, the brain can be almost normally activated in the early stages of disease, although not during moderate-severe dementia. Thus, in vivo imaging during graded parametric stimulation can be used to evaluate synaptic efficacy, and the ability of therapeutic intervention to ameliorate synaptic dysfunction, in pre-symptomatic and diagnosed Alzheimer disease patients.