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 0-470-84641-06Structural Changes in the Aging BrainGandis Mazeika and P. Murali DoraiswamyDuke University Medical Center, Durham, NC, USAIt has long been recognized that aging is associated withprogressive changes in brain structure. The extent to which thebrain is affected by aging is determined by a complex interplay ofenvironmental and genetic factors. Little information is currentlyavailable on the influence of specific factors on brain aging;however, a significant amount of work has been done describingthe aggregate of changes in the aging brain 1 .Methods applied to the study of brain aging have includedanatomic studies and neuroimaging. Each method has specificstrengths and weaknesses, leading at times to confusing and evencontradictory results when comparing studies using differenttechniques. For instance, anatomic studies are subject to fixationartifacts and have rarely controlled for subjects’ cranial size. Onthe other hand, magnetic resonance imaging (MRI) volumetrysuffers from distortion effects due to imperfections in the magneticfield and from difficulty in precisely gauging the gray matter–whitematter junction 2–4 . Furthermore, no consensus exists regardingthe definition of normal brain aging. Attempts at a definition havebeen confounded by various problems, such as difficulties inscreening out individuals with subclinical neurodegenerativedisease, and difficulties in conducting adequate longitudinalstudies.Despite these shortcomings, some information is available onthe regional distribution of age-associated atrophy. A generalprinciple of brain aging that has emerged is that phylogeneticallynewer structures, such as neocortex and neostriatum, tend to showmore age-associated atrophy than phylogenetically older structures,such as the hippocampus and brainstem.NEUROIMAGING STUDIESStudies using various neuroimaging techniques have repeatedlydemonstrated progressive age-related volume loss in widespreadareas in the brain. The overall loss of tissue volume averages0.2%/year, starting in mid-adulthood. Changes are manifestedprimarily by increases in ventricular volume and by corticalatrophy, as measured by increased sulcal markings 9,10 .These changes have significant clinical consequences. Increasesin ventricular volume result in decreased cerebral compliance,rendering the aging brain less resilient to changes in intracranialpressure. Cortical atrophy, on the other hand, causes the brainparenchyma to pull away from the skull table, lengthening corticalbridging veins and increasing vulnerability to subdural hemorrhages.In neuroimaging studies, gray matter volume loss has beenfound to be typically greater than white matter loss. Most affectedis the pre-frontal cortex, with a rate of volume loss of about 0.5%/year. Areas of moderate volume loss include the temporal,parietal and cerebellar cortex. The occipital cortex is relativelyspared, while pons, tectum and hippocampus show minimalchanges with normal aging 9 .Various explanations for these differences in rate of atrophyhave been offered, including regional differences in calciumhomeostasis and expression of inflammatory mediators, such as5-lipoxygenase. None of these hypotheses has been verified.Another important consideration is that distortions associatedwith image acquisition, such as movement artifact and inhomogeneitiesin the magnetic field, may result in insufficient precisionto accurately measure volume changes in smaller structures, suchas the pons.The relative absence of hippocampal changes in normal agingstands in contrast to the dramatic decline in hippocampal volumesobserved during the course of Alzheimer’s disease, frontotemporaldementia and certain other disorders, such as mesial temporalsclerosis. Some researchers have attempted to exploit thisdifference as a means to assist in the diagnosis of Alzheimer’sdisease; however, hippocampal volumetry remains an experimentaltechnique at present 2 .Aside from changes in volume, neuroimaging has revealedother interesting structural changes with aging. The most intenselystudied of these changes is the increasing prevalence of leukoaraiosis,or periventricular white matter hyperintensities. Thesignificance of leuko-araiosis is uncertain, but is thought to berelated to tissue damage as a consequence of microvasculardisease. Leuko-araiosis tends to be more prominent in individualswith hypertension or diabetes, although some degree of perivascularwhite matter changes are found in most individualsabove age 65. To date, no strong relationship has been foundbetween leuko-araiosis and cognitive decline 3,4 .Other noteworthy age-related changes include accumulation ofiron in the striatum, deep cerebellar nuclei and motor cortex andthe deposition of calcium in the pineal gland, choroid plexus andin the walls of the basilar and middle cerebral arteries. The clinicalsignificance of these changes is also uncertain.POST-MORTEM STUDIESOne important question that cannot be addressed by neuroimagingstudies is the extent of actual cell loss occurring withbrain atrophy. A sizable number of gross and microanatomicalpost mortem studies have been conducted to investigate this andother types of anatomical changes that occur in the brain withaging, although so far very few studies have attempted to compareneuroimaging with histologic data in the same individuals 5 .Principles 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