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 0-470-84641-0QUANTITATIVE STRUCTURAL CHANGES IN THE AGEING BRAIN 49Hippocampal Changes and Memory Impairment in Normal PeopleJohn T. O’BrienWolfson Research Centre, Newcastle upon Tyne General Hospital, UKINTRODUCTIONThe nature of age-related cognitive deficits and their relationshipto what is ‘‘normal’’, such as Alzheimer’s disease (AD), remains acontroversial area. It has long been recognized that decline inmany aspects of cognitive performance occurs in the majority ofindividuals as they age. Most interest has focused on memory andvarious labels have been used, including ‘‘benign senescent forgetfulness(BSF)’’, ‘‘age-associated memory impairment (AAMI)’’,‘‘aging-associated cognitive decline (AACD)’’ 1 and, most recently,‘‘mild cognitive impairment (MCI)’’ 2 . MCI describes the conditionwhereby a subjective memory complaint is accompanied byobjective evidence of deficits, usually 1.5 standard deviationsbelow age-corrected norms for a standardized test. Suchindividuals are known to ‘‘convert’’ to clear AD at a rate ofabout 15% per year 3 , in contrast to previous categories, such asBSF, when progression over time does not occur 4 . However,potential entities such as BSF, AAMI, AACD and MCI are stillthe subject of criticism, since it is unknown whether they representa true disorder or a spectrum of the normal population mixedwith those with early, and as yet undiagnosed, AD 5,6 .ROLE OF THE HIPPOCAMPUSThe hippocampus has long been known to be central to thehuman ability to learn new information, particularly for so-calledepisodic memory, i.e. memory for discrete events, and declarativememory, which is memory requiring conscious retrieval 7 . Thiscontrasts with the role of the hippocampus in animals, which isknown to be primarily involved in the formation of spatialmemories. Recent evidence suggests that in humans the hippocampusdoes seem important in the acquisition of new spatialmemories, as well as episodic memory, but is not the actual site ofsuch spatial maps once they have been formed 8 . Differentialfunctional organization of the hippocampus in time and space hasbeen demonstrated 7 , giving support to the view that the main roleof the hippocampus in memory formation is in forming newmemories by capturing the event itself, coding it in time and spaceand binding it together for subsequent processing. Other brainareas (particularly the parahippocampal cortex and the frontalcortex) are also important in forming new memories, especiallyfor encoding 9 . In contrast, other aspects of human memory (e.g.semantic memory) appears not to be dependent on the hippocampus10 although areas such as the anterior temporal pole andfrontal lobe may be important 11 .RELATIONSHIP BETWEEN MEMORYIMPAIRMENT AND HIPPOCAMPAL CHANGESWhile this has been reasonably well established for AD, the sameis not yet true for using the memory impairment associated withageing and conditions such as AACD, AAMI and MCI. An agerelateddecline in temporal lobe and hippocampal volume is foundin most, although not all, studies 12–14 . Reductions in medialtemporal lobe and hippocampal volumes and reduced perfusionand functional imaging in normal individuals with memoryimpairment have been described by some groups 15,16 but notothers 17 , while the excellent spatial memory of taxi drivers hasbeen related to enlargement of the posterior hippocampus in onestudy 18 . Further research is clearly needed. Similarly, some find astrong correlation between the degree of memory impairment innormal elderly people and volumetric change on magneticresonance imaging, while others do not 14,16,17 . More consistent isthe finding that amongst those who already have memoryimpairment, reduced temporal and hippocampal volumes dopredict those who will decline to develop dementia, as opposed tothose who will not 19–22 . However, whether this is simply areflection of the ‘‘contamination’’ of normal memory-impairedindividuals and those with early AD remains unresolved.Neuropathological data are limited, although MCI individualsmay have Alzheimer-type pathology intermediate between thosewith AD and normals 23 . Another candidate for the cause of anyhippocampal damage during ageing would be excessive cortisolexcretion associated with ageing, which is known to be toxic to thehippocampus in animals and possibly in humans 24–26 . Theseremain important avenues for future research. However, otherpossibilities exist for the neurobiological basis of memory andother cognitive impairments in healthy individuals. Generalizedbrain atrophy is known to occur with ageing 27,28 , whilst anincrease in white matter burden, presumably reflecting vascularpathology, occurs and has been linked with cognitive impairmentin some studies 29 .CONCLUSIONDespite the hippocampus being central to new learning in humansand the evidence that memory impairment and hippocampalchanges occur with ageing, further evidence linking the two is stillneeded. Undoubtedly, new views on hippocampal function andtopographical organization, the better definition of the role ofother structures, such as the parahippocampal gyrus and frontallobe, in different memory functions, combined with furtherlongitudinal clinical, electrophysiological, imaging and pathologicalstudies, will provide a clearer answer to this importantquestion in the near future.REFERENCES1. Ritchie K, Touchon J. Mild cognitive impairment: conceptual basisand current nosological status. Lancet 2000; 355: 225–8.2. Petersen RC, Smith GE, Waring SC et al. Mild cognitive impairment:clinical characterization and outcome [published erratum appears inArch Neurol 1999 Jun; 56(6): 760]. Arch Neurol 1999; 56: 303–8.3. Petersen RC, Smith GE, Waring SC et al. Aging, memory, and mildcognitive impairment. Int Psychogeriat 1997; 9: 65–9.4. O’Brien J, Beats B, Hill K et al. Do subjective memory complaintsprecede dementia? A 3 year follow-up of patients presenting withbenign memory problems. Int J Geriat Psychiat 1992; 7: 481–6.5. Milwain E. Mild cognitive impairment: further caution [letter]. Lancet2000; 355: 1018.