The D-allele of ACE insertion/deletion polymorphism is associated with regional white matter volume changes and cognitive impairment in remitted geriatric depression

Prior studies suggested that angiotensin-converting enzyme (ACE) affected vascular homeostasis and degradation of amyloid β (Aβ). It is associated with the therapeutic outcome in major depression. The aim of this study was to investigate the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and structural abnormalities in remitted geriatric depression (RGD), and test the relationship of neuropsychological performances and regional white matter volumes. 31 RGD patients were recruited and neuropsychological tests, magnetic resonance imaging (MRI) and genotype of ACE I/D were examined for each subject. The differences in regional white matter volume were tested between I homozygotes and D-allele carriers (I/D or D/D genotype) by optimized VBM. D-allele carriers exhibited significantly smaller white matter volumes of right superior frontal gyrus (SFG) and right anterior cingulated gyrus (ACG), but had larger volumes of left middle temporal gyrus (MTG) and right middle occipital gyrus (MOG) than I homozygotes (P < 0.001). Meanwhile, there was a significant positive correlation between white matter volume enlargement of left MTG and Symbol Digit Modalities Test (SDMT) (r = 0.456, P = 0.043), and the reduction of right ACG was negatively related to Clock Drawing Test (CDT) performance (r = −0.445, P = 0.050) in D-allele carriers. The finding suggests that ACE can modulates the pathology of RGD, the left MTG and right ACG might be involved in the pathophysiology of cognitive dysfunction in RGD patients.