Evolving Brain Functional Abnormalities in PSEN1 Mutation Carriers: A Resting and Visual Encoding fMRI Study

Article type: Research Article

Authors: Sala-Llonch, Roser^{a; b} | Fortea, Juan^{c; d} | Bartrés-Faz, David^{a; b} | Bosch, Beatriz^{b; c} | Lladó, Albert^{b; c} | Peña-Gómez, Cleofé^a | Antonell, Anna^{b; c} | Castellanos-Pinedo, Fernando^e | Bargalló, Nuria^{b; f} | Molinuevo, José Luis^{b; c} | Sánchez-Valle, Raquel^{b; c; *}

Affiliations: [a] Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain | [b] Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain | [c] Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain | [d] Memory Unit, Department of Neurology, Hospital de Sant Pau, Barcelona, Spain | [e] Department of Neurology, Hospital Virgen del Puerto, Plasencia, Spain | [f] Department of Radiology, Hospital Clínic, Barcelona, Spain

Correspondence: [*] Correspondence to: Raquel Sánchez-Valle, Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Tel.: +34 932275785; Fax: +34 932275783; E-mail: [email protected].

Abstract: PSEN1 mutations are the most frequent cause of familial Alzheimer's disease and show nearly full penetrance. Here we studied alterations in brain function in a cohort of 19 PSEN1 mutation carriers: 8 symptomatic (SMC) and 11 asymptomatic (AMC). Asymptomatic carriers were, on average, 12 years younger than the predicted age of disease onset. Thirteen healthy subjects were used as a control group (CTR). Subjects underwent a 10-min resting-state functional magnetic resonance imaging (fMRI) scan and also performed a visual encoding task. The analysis of resting-state fMRI data revealed alterations in the default mode network, with increased frontal connectivity and reduced posterior connectivity in AMC and decreased frontal and increased posterior connectivity in SMC. During task-related fMRI, SMC showed reduced activity in regions of the left occipital and left prefrontal cortices, while both AMC and SMC showed increased activity in a region within the precuneus/posterior cingulate, all as compared to CTR. Our findings suggest that fMRI can detect evolving changes in brain mechanisms in PSEN1 mutation carriers and support the use of this technique as a biomarker in Alzheimer's disease, even before the appearance of clinical symptoms.

Keywords: Alzheimer's disease, default mode network, functional magnetic resonance imaging, presenilin1, visual memory

DOI: 10.3233/JAD-130062

Journal: Journal of Alzheimer's Disease, vol. 36, no. 1, pp. 165-175, 2013