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J Alzheimers Dis. 2017;55(4):1403-1416. doi: 10.3233/JAD-160223.

Neural Basis of Apathy in Patients with Amnestic Mild Cognitive Impairment.

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Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Departments of Neurology and Cognitive disorders, Hyogo Prefectural Rehabilitation Center at Nishi-harima, Tatsuno, Hyogo, Japan.
Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Radiology, Kinki University Faculty of Medicine, Osakasayama, Osaka, Japan.



Although apathy is associated with damage to the frontal and temporal lobes in Alzheimer's disease (AD), the crucial regions for apathy in patients with amnestic mild cognitive impairment (aMCI) are unknown.


To identify brain regions associated with apathy in aMCI patients.


The subjects of this study were 98 aMCI patients who were entered in our dementia registry between March 1, 2009 and April 30, 2015 and who satisfied our criteria for aMCI. The association between the apathy score of the Neuropsychiatric Inventory and regional gray matter volume was analyzed using voxel-based morphometry. The association between apathy score and regional cerebral blood flow (rCBF) measured with single photon emission computed tomography (SPECT) was analyzed using Statistical Parametric Mapping.


The aMCI patients were classified into aMCI with and without "SPECT images suggestive of AD" (aMCI-AD+ and aMCI-AD-, respectively) based on the Z-score summation analysis method. In aMCI-AD+ (n = 31), apathy was significantly and negatively correlated with gray matter volume in the right caudate nucleus and with rCBF in five regions (left posterior-medial frontal lobe, right superior frontal lobe, bilateral culmen-fusiform gyri, and left occipital lobe). In aMCI-AD-(n = 67), apathy was significantly and negatively correlated with gray matter volumes in five regions but it was not correlated with rCBF in any regions.


In patients with a high probability of being in the aMCI stage of AD, apathy was associated with atrophy of the right caudate nucleus and hypoperfusion in the frontal, temporal and occipital lobes.


Alzheimer’s disease; amnestic mild cognitive impairment; apathy; caudate nucleus; cerebral blood flow; gray matter volume; statistical parametric mapping; voxel-based morphometry

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