Genetic and degenerative disorders primarily causing dementia

Neuroimaging comprises a powerful set of instruments to diagnose the different causes of dementia, clarify their neurobiology, and monitor their treatment. Magnetic resonance imaging (MRI) depicts volume changes with neurodegeneration and inflammation, as well as abnormalities in functional and structural connectivity. MRI arterial spin labeling allows for the quantification of regional cerebral blood flow, characteristically altered in Alzheimer's disease, diffuse Lewy-body disease, and the frontotemporal dementias. Positron emission tomography allows for the determination of regional metabolism, with similar abnormalities as flow, and for the measurement of β-amyloid and abnormal tau deposition in the brain, as well as regional inflammation. These instruments allow for the quantification in vivo of most of the pathologic features observed in disorders causing dementia. Importantly, they allow for the longitudinal study of these abnormalities, having revealed, for instance, that the deposition of β-amyloid in the brain can antecede by decades the onset of dementia. Thus, a therapeutic window has been opened and the efficacy of immunotherapies directed at removing β-amyloid from the brain of asymptomatic individuals is currently being tested. Tau and inflammation imaging, still in their infancy, combined with genomics, should provide powerful insights into these disorders and facilitate their treatment.