Cognitive, Genetic, and Brain Perfusion Factors Associated with Four Year Incidence of Alzheimer's Disease from Mild Cognitive Impairment

Article type: Research Article

Authors: Alegret, Montserrat^{a; *} | Cuberas-Borrós, Gemma^{b; c} | Espinosa, Ana^a | Valero, Sergi^{a; d} | Hernández, Isabel^a | Ruíz, Agustín^a | Becker, James T.^{e; f; g} | Rosende-Roca, Maitée^a | Mauleón, Ana^a | Sotolongo, Oscar^a | Castell-Conesa, Joan^{b; c} | Roca, Isabel^{b; c} | Tárraga, Lluís^a | Boada, Mercè^a

Affiliations: [a] Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain | [b] Nuclear Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain | [c] Hospital Universitari Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain | [d] Psychiatry Department, Hospital Universitari Vall d'Hebron, CIBERSAM, Universitat Autònoma de Barcelona, Barcelona, Spain | [e] Departments of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA | [f] Departments of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA | [g] Departments of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence: [*] Correspondence to: Montserrat Alegret, PhD, Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain. Tel.: +34 93 4304720; Fax: +34 93 4193542; E-mail: malegret@fundacioace.com.

Abstract: Background:There is a range of factors that predict the development of Alzheimer’s disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI). Objectives:To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI. Methods:From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation. Results:The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia. Conclusion:Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD.

Keywords: Alzheimer's disease, brain SPECT, cerebral perfusion, four-year follow-up, longitudinal, mild cognitive impairment, prospective, visual memory

DOI: 10.3233/JAD-132516

Journal: Journal of Alzheimer's Disease, vol. 41, no. 3, pp. 739-748, 2014