Neurobiology of Aging 32 (2011) 1542–1557 Single domain amnestic MCI: A multiple cognitive domains fMRI investigation D. Lenzi a,b,∗ , L. Serra c , R. Perri d , P. Pantano a,b , G.L. Lenzi a,b , E. Paulesu e , C. Caltagirone d,f , M. Bozzali c , E. Macaluso c a Department of Neurological Sciences, Università “Sapienza”, Viale dell’università 30, 00185 Rome, Italy b Centro per lo Studio delle Funzioni Mentali dell’Uomo, University of Rome La Sapienza, viale dell’università 30, 00185 Rome, Italy c Neuroimaging Laboratory, Fondazione Santa Lucia, via Ardeatina 306, 00147 Rome, Italy d Clinical and Behavioural Neurology Laboratory, Fondazione Santa Lucia, via Ardeatina 306, 00147 Rome, Italy e Università degli Studi di Milano – Bicocca, Dipartimento di Psicologia, Piazza dell’Ateneo Nuovo 1, 20126 Milan, Italy f Department of Neuroscience, University of Rome ‘Tor Vergata’, Via Mont Pelier 1, 00133 Rome, Italy Received 23 March 2009; received in revised form 12 September 2009; accepted 27 September 2009 Available online 31 October 2009 Abstract Amnestic mild cognitive impairment (a-MCI) is associated with the highest annual incidence of conversion to Alzheimer’s disease (AD) (10–15%). a-MCI patients may have only a memory deficit (single domain: sd-a-MCI) or additional dysfunctions affecting other cognitive domains (multiple domain: md-a-MCI). Using functional magnetic resonance imaging (fMRI), we investigated brain activation in 16 sd-a-MCI patients and 14 controls during four different tasks assessing language, memory, attention and empathy functions. We found greater activation in sd-a-MCI compared with controls in the left inferior temporal gyrus (language), the right superior temporal gyrus (memory) and the right dorsal precentral gyrus (attention). Moreover, patients’ activation correlated significantly with neuropsychological scores obtained at tests exploring the corresponding function. These findings indicate that fMRI is sensitive to detect early changes occurring in AD pathology and that individuals with sd-a-MCI show increased activation in multiple task-related brain regions. We suggest that these functional changes relate to the development of early compensatory mechanisms that reduce cognitive deficits associated with the progressive accumulation of brain damage. © 2009 Elsevier Inc. All rights reserved. Keywords: Single domain amnesic mild cognitive impairment; fMRI; Multiple cognitive investigation 1. Introduction Mild cognitive impairment (MCI) defines a transitional state along a continuous spectrum that goes from normal aging to fully developed dementia (Petersen et al., 2001). This clinical classification is critical to the identification of individuals at high risk for developing Alzheimer’s disease (AD). From this perspective, MCI represents an interesting target for the investigation of AD patho-physiology, and also for the identification of patients at early clinical stages of AD, ∗ Corresponding author at: Department of Neurological Sciences, Univer- sità “Sapienza”, Viale dell’università 30, 00185 Rome, Italy. Tel.: +39 338 6235186; fax: +39 06 4457376. E-mail address: delia.lenzi@gmail.com (D. Lenzi). who might enter clinical trials at a time when their cognitive functions are still relatively preserved. MCI patients typically complain of cognitive deficits that do not interfere, or interfere only mildly, with their everyday- life activities. Early cognitive dysfunctions in MCI patients can be multifaceted (Petersen et al., 2001), in most cases including memory deficits and leading to the classification of a-MCI (amnestic MCI: see Petersen, 2004). a-MCI is widely considered as the condition most commonly associated with a high risk of conversion to AD (10–15%; see Petersen et al., 2001), and is therefore regarded by most authors as a prodromal state of AD (Gauthier et al., 2006). However, a- MCI includes a heterogeneous population of subjects. While 10–15% of a-MCI patients convert to AD, a small proportion of a-MCI patients can remain stable with an isolated cognitive 0197-4580/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2009.09.006