Molecular Neuroimaging in Vascular Cognitive Impairment.

Age-related cognitive impairment is arguably the greatest looming threat to aging populations in both the developed and developing world. Emerging evidence indicates that cerebral small vessel disease (SVD) is a major contributor to cognitive impairment, highlighting the importance of improved understanding of the molecular and physiological mechanisms leading to vascular brain injury. As a result, 2 of the 3 highest priority research areas for the next 5 to 10 years identified by National Institute of Neurological Disorders and Stroke’s (NINDS) Workgroup on Stroke Prevention Research in 2012 were focused on prevention of vascular cognitive impairment (VCI) and imaging biomarkers in stroke prevention. This important initiative of NINDS has further accelerated the neuroimaging research in VCI that was blossoming over the preceding 10 years. Novel magnetic resonance imaging (MRI) markers of ischemic and hemorrhagic tissue damage in the brain have been identified, and their associations with the underlying cerebrovascular pathologies and resulting cognitive changes are extensively studied. MRI-based studies yielded a large gamut of imaging markers that mediate vascular contributions to dementia. Silent infarcts, lacunes, white matter hyperintensities (WMH) on fluid-attenuated inversion recovery MRI, fractional anisotropy and mean diffusivity changes, and acute punctate infarcts on diffusion weighted MRI are examples of ischemic markers that have been increasingly studied during the past decade. Cerebral microbleeds (CMB) and cortical superficial siderosis are subtle hemorrhagic lesions visible on T2*-MRI, and they serve as key markers of the most common SVDs that contribute to VCI in elderly. Enlarged perivascular spaces (EPVS), identified on T1and T2-weighted MRIs by radiologists for over 2 decades, are emerging as another VCI-related marker, especially because of their association with the type of SVD. Functional MRI provided measures of vascular dysfunction and resting-state functional connectivity, whereas diffusion tensor imaging can identify subtle but important changes in structural connectivity. The aforementioned structural and functional imaging techniques resulted in an unprecedented boom in VCI research, but a good understanding of disease mechanisms and development of therapeutic approaches rely on detection of molecular changes that occur during the pathological processes. Development of novel positron emission tomography (PET) tracers and advances in MRI allowed the use of cutting-edge molecular neuroimaging techniques in VCI research that make the focus of the current topical review. The information obtained from well-designed studies published within the past few years will be critically reviewed, and preliminary data from ongoing efforts will be presented.