Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-07Anatomy of the Aging BrainJohn J. Campbell III 1 and C. Edward Coffey 1,2Departments of 1 Psychiatry, and 2 Neurology, Henry Ford Health System, Detroit, MI, USAINTRODUCTIONKnowledge of the spectrum and extent of changes in brainmorphology that occur with ‘normal aging’ is critical to anyunderstanding of age-related illnesses, such as dementia. Prior tothe recent introduction of advanced brain imaging techniques,post mortem studies served as the only source of informationregarding the anatomy of the aging human brain. A commonfinding among them was a reduction of brain size with age,consisting initially (in the seventh decade) of atrophy of the graymatter (widening of sulci and thinning of gyri), followed by adecline in the volume of the white matter (in the eighth and ninthdecades of life) 1 . The cortical atrophy appeared to be mostprominent in the frontal and parietal parasagittal areas andconsisted of a decrease in the volume rather than in the number ofindividual neurons 2 . Ventricular enlargement was also observed,but the degree of the dilatation was variable among the differentstudies 1,3 .There are several sources of error inherent to post mortemstudies. Most of the studies included subjects with very differentcauses of death, which themselves can lead to a variety of changesin brain morphology; in particular, the cause of death may bequite different for young vs. elderly cohorts. Another disadvantageof the post mortem measurements is that the brain can bealtered in unpredictable ways prior to tissue processing, as well asduring the process of fixation 4,5 .Many of these problems have now been obviated by thedevelopment of imaging techniques, such as computed X-raytomography (CT) and magnetic resonance imaging (MRI), whichhave provided an opportunity to examine the human brain invivo 105 . In this chapter, we critically review those brain imagingstudies that have investigated age-related changes in brainanatomy. Any understanding of these data must begin, however,with a discussion of relevant methodological issues.respect to variables that could influence brain anatomy. Forexample, differences between elderly and non-elderly cohorts withrespect to nutrition or socioeconomic status could be associatedwith differences in brain morphology that have nothing to do withaging per se. The survivor effect refers to the biased selection ofvery healthy individuals, since those with underlying diseasesusually die earlier and do not have the chance to be selected forstudy.Longitudinal studies follow the same subjects with repeatedexaminations over time. Data acquisition is very labor-intensiveand takes place over long periods of time. Longitudinal studiesare limited by a period effect (changes over time in themethodology of the study) and an attrition effect (dropouts), inwhich the participants available at the end of the study may bequite different from the sample recruited initially.Sample SelectionAge-related changes in brain morphology will obviously dependcritically upon the criteria used to select the population understudy. ‘Normal’ volunteers from the community may differmarkedly from patients with ‘clinically normal’ brain CT orMRI scans with respect to variables that may influence brainanatomy. Medical and psychiatric illness, smoking, alcoholconsumption, nutrition, education, environment, sex and heightare just some of the variables that must be considered whencomparing brain anatomy among individuals. Population heterogeneityis especially great among the elderly, and Rowe andKahn 6 have suggested a distinction between ‘usual aging’ (noclinically obvious brain disease) and ‘successful aging’ (minimaldecline in neurobiologic function in comparison with youngsubjects). The increased variability of measures of brain anatomyseen in ‘normal’ elderly populations may be due in part to therelative mix of subjects with usual vs. successful aging.ISSUES OF METHODOLOGYStudy DesignStudies of the aging brain can be classified as either cross-sectionalor longitudinal. Cross-sectional studies select subjects from all agegroups and examine them during roughly the same time period.Subject recruitment is relatively easy and large amounts of datacan be acquired and analyzed in a short period of time. Two mainlimitations are inherent to cross-sectional studies; the secular orgeneration effect and the survivor or cohort effect. The seculareffect refers to differences among successive generations withImaging TechnologyBrain imaging techniques differ in their safety, sensitivity andanatomic resolution. One of the oldest methods for in vivo brainimaging is pneumoencephalography (PEG). PEG is unsuitableethically for the study of the normal brain, due to its associateddiscomfort and high morbidity rate. The procedure itself may alsodirectly affect the size of the cerebrospinal fluid (CSF) spaces 7 .These problems limit the application of this technique to patientswith sufficient neurologic symptomatology to warrant such anPrinciples and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd