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rCBF and cognitive impairment changes assessed by SPECT and ADAS-cog in late-onset Alzheimer’s disease after 18 months of treatment with the cholinesterase inhibitors donepezil or galantamine

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Abstract

Late-onset Alzheimer’s disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.

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Funding

This research did not receive any specific grant from any funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Psychiatry, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, 299-0111, Japan

    Yukihiko Shirayama, Michio Takahashi, Kouhei Yoshino & Koichi Sato

  2. Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan

    Yasunori Oda, Kouhei Yoshino & Masaomi Iyo

  3. Department of Radiology, Teikyo University Chiba Medical Center, Ichihara, Japan

    Toshiyuki Okubo

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  1. Yukihiko Shirayama
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  2. Michio Takahashi
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  3. Yasunori Oda
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  4. Kouhei Yoshino
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  5. Koichi Sato
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  6. Toshiyuki Okubo
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  7. Masaomi Iyo
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Correspondence to Yukihiko Shirayama.

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Conflict of interest

Dr. Shirayama has received research support from Eli Lilly, Eisai, MSD, Pfizer, Takeda and Mitsubishi-Tanabe. Dr. Iyo has received consultant fees from Eli Lilly, Sumitomo, Dainippon, Pfizer and Abbott.

Drs. Takahashi, Oda, Yoshino and Sato have no competing interests.

Ethical approval

All procedures performed in this study were in accordance with the ehical standards of the institutional research committee and with 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the ehics committee of Teikyo University Chiba Medical Center.

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Informed consent was obtained from all individual participants included in this study.

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Shirayama, Y., Takahashi, M., Oda, Y. et al. rCBF and cognitive impairment changes assessed by SPECT and ADAS-cog in late-onset Alzheimer’s disease after 18 months of treatment with the cholinesterase inhibitors donepezil or galantamine. Brain Imaging and Behavior 13, 75–86 (2019). https://doi.org/10.1007/s11682-017-9803-y

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