Early detection of Alzheimer’s disease using neuroimaging Lisa Mosconi * , Miroslaw Brys, Lidia Glodzik-Sobanska, Susan De Santi, Henry Rusinek, Mony J. de Leon Center for Brain Health MHL-400, New York University School of Medicine, 560 1st Avenue, New York, NY 10016, USA Received 26 April 2006; received in revised form 3 May 2006; accepted 5 May 2006 Available online 12 July 2006 Abstract Neuroimaging is being increasingly used to complement clinical assessments in the early detection of Alzheimer’s disease (AD). Struc- tural magnetic resonance imaging (MRI) and metabolic positron emission tomography (FDG-PET) are the most clinically used and promising modalities to detect brain abnormalities in individuals who might be at risk for AD but who have not yet developed symp- toms. The knowledge of established risk factors for AD enabled investigators to develop enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study duration. The present review focuses on the results obtained by MRI and FDG-PET studies that examined the preclinical AD stages in several at risk populations: (1) individuals from families with autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI), particularly in memory, who are at very high risk for declining to AD with an estimated decline rate of 10–30% per year, (3) normal young and middle-age subjects carriers of known susceptibility genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these studies show that the use of imaging for the early detection of AD is successful even in the earlier stages of disease when clinical symptoms are not fully expressed and the regional brain damage may be limited. Ó 2006 Elsevier Inc. All rights reserved. Keywords: Alzheimer’s disease; Early detection; Magnetic resonance imaging (MRI); Positron emission tomography (FDG-PET); Normal aging; Mild cognitive impairment 1. Introduction Alzheimer’s disease (AD) is the most common form of dementia in the elderly and one of the most serious health problems in the industrialized world. The elderly are the most rapidly growing part of the population, and increases in life expectancy will inevitably lead to a further increase in the prevalence of AD. At present, AD afflicts 10% of individuals over 65 years of age, and more than 50% of persons over 80 years, with age-associated cognitive impairments affecting 10 times as many individuals (Brookmeyer et al., 1998). The risk of developing AD doubles approximately every 5 years between the ages of 65 and 85 years, and therefore, as the baby boomer gener- ation ages, it is estimated that in 30 years, 15–20 million elderly nationwide may have some cognitive disability (Brookmeyer et al., 1998; Petersen et al., 1999). The demo- graphics of aging thus suggest a great need to accurately diagnose AD and to specifically distinguish it from the many other possible causes of cognitive impairment. Remarkable progress has been made in the understanding of the cascade of molecular events leading to AD. In the last decade, genetic abnormalities have been identified, new pathophysiological mechanisms discovered, therapeu- tic agents approved, and diagnostic tests developed. Nonetheless, fundamental questions pertaining to AD pathogenesis remain unanswered and the lack of specific biological markers hinders the accurate identification and management of AD. With the development of specific and effective prevention treatments, improved early detec- tion of AD will be increasingly critical for medical care. As strategies to delay disease progression, and possibly 0531-5565/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2006.05.016 * Corresponding author. Tel.: +1 212 263 3255; fax: +1 212 263 3270. E-mail address: lisa.mosconi@med.nyu.edu (L. Mosconi). www.elsevier.com/locate/expgero Experimental Gerontology 42 (2007) 129–138