title: Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease.
abstract: Neuropsychiatric symptoms (NPSs) often occur in early-age-of-onset Alzheimer's disease (EOAD) and cluster into sub-syndromes (SSy). The aim of this study was to investigate the association between18F-FDG-PET regional and connectivity-based brain metabolic dysfunctions and neuropsychiatric SSy. NPSs were assessed in 27 EOAD using the Neuropsychiatric Inventory and further clustered into four SSy (apathetic, hyperactivity, affective, and psychotic SSy). Eighty-five percent of EOAD showed at least one NPS. Voxel-wise correlations between SSy scores and brain glucose metabolism (assessed with18F-FDG positron emission tomography) were studied. Interregional correlation analysis was used to explore metabolic connectivity in the salience (aSN) and default mode networks (DMN) in a larger sample of EOAD (N = 51) and Healthy Controls (N = 57). The apathetic, hyperactivity, and affective SSy were highly prevalent (>60%) as compared to the psychotic SSy (33%). The hyperactivity SSy scores were associated with increase of glucose metabolism in frontal and limbic structures, implicated in behavioral control. A comparable positive correlation with part of the same network was found for the affective SSy scores. On the other hand, the apathetic SSy scores were negatively correlated with metabolism in the bilateral orbitofrontal and dorsolateral frontal cortex known to be involved in motivation and decision-making processes. Consistent with these SSy regional correlations with brain metabolic dysfunction, the connectivity analysis showed increases in the aSN and decreases in the DMN. Behavioral abnormalities in EOAD are associated with specific dysfunctional changes in brain metabolic activity, in particular in the aSN that seems to play a crucial role in NPSs in EOAD. Hum Brain Mapp 37:4234-4247, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Ballarini
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Iaccarino
authors.affiliation: Department of Neurology, San Raffaele Hospital, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California.
authors.forename: Nagehan
authors.initials: N
authors.lastname: Ayakta
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|San Raffaele Hospital, Nuclear Medicine Unit, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
mesh_terms: D000339:Affect / Q000502:physiology; D017668:Age of Onset; D000544:Alzheimer Disease / Q000145:classification / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D057565:Apathy / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D019275:Radiopharmaceuticals; D012189:Retrospective Studies
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: early onset Alzheimer's Disease; frontal lobe; functional networks; metabolic connectivity; neuropsychiatric subsyndromes; positron-emission tomography