Research Article: Correlation of hippocampal atrophy with hyperhomocysteinemia in hemodialysis patients: An exploratory pilot study

Date Published: April 10, 2017

Publisher: Public Library of Science

Author(s): Kyoko Maesato, Takayasu Ohtake, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Hidekazu Moriya, Sumi Hidaka, Shuzo Kobayashi, Johannes Boltze.


Cognitive impairment is one of the important critical issues in hemodialysis (HD) patients. However, the associating factors of brain atrophy in HD patients have not been fully elucidated.

Brain magnetic resonance imaging (MRI) was performed in 34 of total 72 HD outpatients in our dialysis center. These MRI images were analyzed by an application software; Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD). VSRAD quantitatively calculates the extent of brain atrophy (percent of volume reduction) comparing with a MRI imaging database of 80 age-matched healthy controls. The extent of both hippocampal and whole-brain atrophy was evaluated with possible contributing factors.

In all patients, the mean extent of hippocampal atrophy was 27.3%, and the mean extent of whole-brain atrophy was 11.2%. The extent of hippocampal atrophy was significantly correlated with low body mass index (BMI), total serum homocysteine (tHcy) levels, and brachial-ankle pulse wave velocity (baPWV). The extent of whole-brain atrophy showed significant correlations with age, hypoalbuminemia, and baPWV. Based on the multiple regression analysis, tHcy was an independent determinant of hippocampal atrophy (β = 0.460, R2 = 0.189, P<0.01); while age was an independent determinant of whole-brain atrophy (β = 0.594, R2 = 0.333, P<0.01). In this exploratory pilot study, hippocampal atrophy was significantly correlated with hyperhomocysteinemia in HD patients.

Partial Text

Chronic kidney disease (CKD) is classified as one of the major risk factors for the progression of atherosclerotic disease [1]. Furthermore, CKD and atherosclerosis are forming vicious cycle with interacting each together. Higher serum levels in homocysteine (total homocysteine; tHcy) are also known to be as an independent risk factor for atherosclerotic disease [2]. In hemodialysis (HD) patients, serum tHcy levels are known to be highly elevated frequently [3].

Tokushukai group ethical committee in the Mirai Iryo Research Center Inc. permits this study. Permission number of this study; TGE00396-061.

Our cross-sectional exploratory pilot study showed that the %HP extent was correlated with BMI, tHcy, and baPWV in a single correlation analysis, of which tHcy was an independent determinant of %HP extent. The %WB extent was correlated with age, hypoalbuminemia, and baPWV as well. Among these parameters, age was an independent determinant of %WB extent.

In conclusion, tHcy was an independent determinant of hippocampal atrophy while age was an independent determinant of whole-brain atrophy in this exploratory pilot study. Although we could not provide the causative relationship, our study showed association between hyperhomocysteinemia and hippocampal atrophy. Because hippocampal and whole-brain atrophy is thought to be associated with cognitive dysfunction, influence of serum tHcy levels on longitudinal changes of hippocampal atrophy and cognitive function should be clarified in the future.




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