Brain Aging and Its Modifiers: Insights from in Vivo Neuromorphometry and Susceptibility Weighted Imaging NAFTALI RAZ a , KAREN M. RODRIGUE a , and E. MARK HAACKE b aInstitute of Gerontology and Department of Psychology, Wayne State University, Detroit, Michigan, USA bDepartment of Radiology, Wayne State University School of Medicine, Detroit, Michigan, USA Abstract Aging is marked by individual differences and differential vulnerability of cognitive operations and their neural substrates. Cross-sectional studies of brain volume reveal greater age-related shrinkage of the prefrontal cortex (PFC) and the hippocampus than in the entorhinal and primary visual cortex. Longitudinal studies of regional brain shrinkage indicate that when individual differences are controlled, larger and broader shrinkage estimates are evident, with most polymodal cortices affected to the same extent. The mechanisms of age-related shrinkage are unclear. Vascular risk factors may exacerbate brain aging and account for some of the observed declines as both the PFC and the hippocampus show elevated vulnerability to hypertension. MRI techniques that are sensitive to small vessels function, tissue oxygenation, and perfusion may be especially well suited to study brain aging and its vascular modifiers. We present an example of one such technique, susceptibility weighted imaging (SWI), that allows direct measurement of T2* values that reflect deoxy- to oxyhemoglobin fraction in blood vessels and iron deposits in cerebral tissue. The T2* shortening is associated with advanced age, but the effect is significantly stronger in the PFC and the hippocampus than the entorhinal and visual cortices. Moreover, T2* is shorter in hypertensive participants than in their matched normotensive counterparts, and the difference is especially prominent in the hippocampus, thus mirroring the findings of the neuromorphometric studies. Future research on brain aging would benefit from combining structural and metabolic techniques in a longitudinal design, as such studies will allow examination of leading–trailing effects of those factors. Keywords aging; MRI; brain; longitudinal; vascular risk; susceptibility weighted imaging; deoxyhemoglobin; iron INTRODUCTION Aging is marked by substantial variability across individual organisms, among organs and systems, and within organs’ cellular elements. Postmortem (PM) studies reveal a plethora of age-related differences in human brain specimens: reduced brain size, expansion of cerebral ventricles and sulci, loss of myelin, region-specific loss of neuronal bodies, rarefication of cerebral vasculature, and reduced synaptic density. 1-3 However, PM methods preclude examination of longitudinal trajectories of aging and make study of cognitive correlates of brain differences rather difficult. Address for correspondence: Naftali Raz, Ph. D., Institute of Gerontology, Wayne State University, 87 E Ferry St., 226 Knapp Bldg., Detroit, MI 48202. Voice: 313−577−2297; fax: 508−256−5689. nraz@wayne.edu. NIH Public Access Author Manuscript Ann N Y Acad Sci. Author manuscript; available in PMC 2009 January 23. Published in final edited form as: Ann N Y Acad Sci. 2007 February ; 1097: 84–93. doi:10.1196/annals.1379.018. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript