Memory complaints and increased rates of brain atrophy: risk factors for mild cognitive impairment and Alzheimer’s disease H. A. Archer 1 , J. Kennedy 1 , J. Barnes 1 , T. Pepple 1 , R. Boyes 1 , K. Randlesome 1 , S. Clegg 1 , K. K. Leung 1,2 , S. Ourselin 1,2 , C. Frost 1,3 , M. N. Rossor 1 and N. C. Fox 1 1 Dementia Research Centre, UCL Institute of Neurology, London, UK 2 Centre for Medical Image Computing, Department of Medical Physics and Bioengineering, UCL, UK 3 Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK Correspondence to: Dr H. A. Archer, E-mail: harcher@dementia.ion.ucl.ac.uk Aim: To determine rates of cerebral atrophy in individuals with symptoms of memory loss but no objective cognitive impairment (SNCI) and their association with future cognitive decline. Methods: Thirty-two SNCI subjects, 16 with mild cognitive impairment (MCI) and 27 control subjects had clinical assessment and magnetic resonance imaging at baseline and 1 year later. Rates of whole brain atrophy (WBA), hippocampal atrophy (HA) and ventricular enlargement (VE) were measured. Our outcome was clinical diagnosis at 2 years after entry into the study. Results: The MCI group had greater rates of WBA, HA and VE than both controls and SNCI subjects. As a group SNCI subjects did not have significantly greater rates of atrophy than the controls. However, SNCI subjects who progressed to MCI or dementia had increased rates of atrophy compared with those who remained stable. Discussion: Individuals with memory complaints but no objective memory deficits, who progress to MCI or dementia, have increased rates of cerebral atrophy. Copyright # 2010 John Wiley & Sons, Ltd. Key words: memory; MCI; MRI; brain atrophy History: Received 5 July 2009; Accepted 22 September 2009; Published online 18 January 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/gps.2440 Introduction Alzheimer’s disease (AD) is the commonest cause of dementia. The strongly age-related incidence of AD combined with aging populations means the preva- lence of AD is expected to rise rapidly over coming decades (Ferri et al., 2005). Symptomatic treatments for Alzheimer’s disease are available and new biotherapeutic agents with the potential to modify the disease process are being developed. With trials of these drugs underway it is crucial to have robust techniques to help identify those individuals who will benefit from treatment. Once an individual has profound memory impairment and a change in cerebral structure consistent with AD, signi- ficant, irreversible brain cell loss has already taken place. As knowledge of the pathogenesis of AD has increased, it has become apparent that these changes in cerebral structure and function can take place prior to the development of symptoms of AD (Ridha et al., 2006). Using disease-modifying treatments early in the disease process, when the amyloid and hyperpho- sphorylated tau burden is lower, is likely to have a greater effect on preservation of cognitive function than if administered when clear functional disability and cognitive impairment are present. The identifi- cation of individuals with early AD will also be important in providing an appropriate population within which to assess the benefits of these therapies. The identification of individuals with incipient AD remains problematic. Although symptoms of memory loss are one of the first signs of AD, they are also RESEARCH ARTICLE Copyright # 2010 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2010; 25: 1119–1126.