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Research paper
Apathy correlates with prefrontal amyloid β deposition in Alzheimer's disease
  1. Takaaki Mori1,2,
  2. Hitoshi Shimada1,3,
  3. Hitoshi Shinotoh1,4,
  4. Shigeki Hirano1,5,
  5. Yoko Eguchi1,
  6. Makiko Yamada1,
  7. Ryuji Fukuhara2,
  8. Satoshi Tanimukai2,
  9. Ming-Rong Zhang1,
  10. Satoshi Kuwabara5,
  11. Shu-ichi Ueno1,2,
  12. Tetsuya Suhara1
  1. 1Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan
  2. 2Department of Neuropsychiatry, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, Japan
  3. 3Section for Human Neurophysiology, Research Center for Frontier Medical Engineering, Chiba University, Chiba, Japan
  4. 4Neurology Chiba, Chiba, Japan
  5. 5Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan
  1. Correspondence to Tetsuya Suhara, Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 260-8555, Japan; suhara{at}


Objective Neuropsychiatric symptoms affect many patients with Alzheimer's disease (AD). (11C)Pittsburgh Compound-B (PIB) positron emission tomography (PET) has enabled the in vivo visualisation of brain amyloid-β (Aβ) deposition. This study exploratively investigated the correlation between brain Aβ deposition measured by (11C)PIB PET and neuropsychiatric symptoms in AD.

Methods Participants were 28 patients (15 women, 13 men) with PIB-positive AD. Clinical assessments included Mini-Mental State Examination, Clinical Dementia Rating scale, neuropsychiatry inventory (NPI) and frontal assessment battery. All patients underwent three-dimensional T1-weighted MRI and (11C)PIB PET. The distribution volume ratio (DVR), an index of (11C)PIB retention and, thus, Aβ deposition, was estimated voxel by voxel from (11C)PIB PET data with partial volume correction. Voxel-based correlation analysis was performed to assess the relationships between DVR and each NPI subscale. Additionally, voxel-based analysis of covariance (ANCOVA) of the DVR images was performed between Patients with AD with and without each neuropsychiatric symptom. Voxel-based morphometry analysis of MRI was also performed.

Results Apathy subscale was correlated with (11C)PIB retention in the bilateral frontal and right anterior cingulate. (11C)PIB retention was greater in the bilateral frontal cortex of patients with AD with apathy than those of without apathy. Overlapping areas between the two analyses were the bilateral orbitofrontal gyrus and left superior frontal gyrus. Other NPI subscales were not correlated with (11C)PIB retention. Voxel-based morphometry analysis of MRI showed no significant cluster of correlation between grey matter volume and NPI subscales.

Conclusions This study revealed that prefrontal Aβ deposition correlates with apathy.

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