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Hum Brain Mapp. 2016 Dec;37(12):4234-4247. doi: 10.1002/hbm.23305. Epub 2016 Jul 13.

Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease.

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Università Vita-Salute San Raffaele, Milan, Italy.
In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California.
Helen Wills Neuroscience Institute, University of California, Berkeley, California.
San Raffaele Hospital, Nuclear Medicine Unit, Milan, Italy.


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 between 18 F-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 with 18 F-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.


early onset Alzheimer's Disease; frontal lobe; functional networks; metabolic connectivity; neuropsychiatric subsyndromes; positron-emission tomography

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