Neuroimaging statistical approaches for determining neural correlates of Alzheimer's disease via positron emission tomography imaging

Alzheimer's disease (AD) is a degenerative disorder involving significant memory loss and other cognitive deficits, manifesting as a progression from normal cognitive functioning to mild cognitive impairment to AD. The sooner an accurate diagnosis of probable AD is made, the easier it is to manage symptoms and plan for future therapy. Functional neuroimaging stands to be a useful tool in achieving early diagnosis. Among the many neuroimaging modalities, positron emission tomography (PET) provides direct regional assessment of, among others, brain metabolism, cerebral blood flow, amyloid deposition—all quantities of interest in the characterization of AD. However, there are analytic challenges in identifying early indicators of AD from these high‐dimensional imaging data sets, and it is unclear whether early indicators of AD are more likely to emerge in localized patterns of brain activity or in patterns of correlation between distinct brain regions. Early PET‐based analyses of AD focused on alterations in metabolic activity at the voxel‐level or in anatomically defined regions of interest. Other approaches, including seed‐voxel and multivariate techniques, seek to characterize metabolic connectivity by identifying other regions in the brain with similar patterns of activity across subjects. We briefly review various neuroimaging statistical approaches applied to determine changes in metabolic activity or metabolic connectivity associated with AD. We then present an approach that provides a unified statistical framework for addressing both metabolic activity and connectivity. Specifically, we apply a Bayesian spatial hierarchical framework to longitudinal metabolic PET scans from the Alzheimer's Disease Neuroimaging Initiative.