FDG PET and the genetics of dementia

Abstract

Dementias are the most common neurodegenerative diseases and they are increasingly becoming a major public health problem. The most common form of dementia, affecting over 20 million people worldwide, is Alzheimer's disease (AD). AD is a neurodegenerative disease of the central nervous system mainly found in older adults, with an incidence that increases with age. With the development of newer technologies, including genetic screening technologies and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined; indeed, these approaches are able to provide support not only in the clinical diagnosis of dementia, but also in its presymptomatic evaluation. Many researchers agree that early identification of AD, before abnormal accumulation of amyloid and tau proteins, could provide an opportunity to hinder the progression of the disease. [18F]2-fluoro-2-deoxy-d-glucose (FDG) PET studies have shown that decreased glucose metabolism in AD precedes clinical diagnosis and that the degree of clinical disability in AD correlates closely with the magnitude of the reduction in brain glucose metabolism. Data on presymptomatic mutation carriers from families with known early-onset autosomal dominant AD (familial AD) show reductions in the cerebral metabolic rate of glucose (CMRglc), consistent with the expected AD PET pattern, in the absence of severe atrophy on MRI. These results suggest that PET CMRglc measures have the potential to serve as preclinical biomarkers of dementia, useful also for tracking disease progression. This review highlights the role of genetics and FDG PET in understanding the pathogenesis of dementia. © 2013 Italian Association of Nuclear Medicine and Molecular Imaging.