Jing Li1, Qihao Zhang2, Nan Zhang3, Lingfei Guo3. 1. Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. 2. Department of Radiology, Weill Cornell Medical College, New York, NY, United States. 3. Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
Abstract
PURPOSE: Brain iron accumulation has been suggested as a pathomechanism in patients with type 2 diabetes mellitus (T2DM) with cognitive impairment. This research aims to examine the total-brain pattern of iron accumulation in relation to executive function decline in patients with T2DM by voxel-based quantitative susceptibility mapping (QSM) analysis. MATERIALS AND METHODS: A total of 32 patients with T2DM and 34 age- and sex-matched healthy controls (HCs) were enrolled in this study. All participants underwent brain magnetic resonance examination, and 48 individuals underwent cognitive function assessments. Imaging data were collected with three-dimensional fast low-angle shot sequences to achieve magnitude as well as phase images. Using voxel-based QSM analysis, we compared the voxel-wise susceptibility values of the whole brain among groups and explored whether the susceptibility values had correlations with cognitive data. RESULTS: Among the 66 participants, cognitive function was estimated in 23 patients with T2DM (11 males and 12 females; average age, 64.65 ± 8.44 years) and 25 HCs (13 males and 12 females; average age, 61.20 ± 7.62 years). T2DM patients exhibited significantly (t = 4.288, P < 0.001) lower Montreal Cognitive Assessment (MoCA) scores [T2DM, 27 (27, 28); HCs, 29 (28, 29); normal standard ≥ 26)] and higher Trail-making Test (TMT)-A/TMT-B scores [71 (51, 100)/185 (149, 260)] than HCs [53 (36.5, 63.5)/150 (103, 172.5)] (Z = 2.612, P = 0.009; Z = 2.797, P = 0.005). Subjects with T2DM showed significantly higher susceptibility values than HCs in the caudate/putamen/pallidum, frontal inferior triangular gyrus, and precentral gyrus on the right hemisphere. In contrast (HC > T2DM), no region showed a significant difference in susceptibility values between the groups. The correlation analysis between susceptibility values and cognitive function scores was tested by voxel-based susceptibility value with sex and age as covariates. After multiple comparison correction, in T2DM patients, the left thalamus showed a significant relationship with TMT-A (R 2 = 0.53, P = 0.001). The right thalamus and left thalamus showed a significant relationship with TMT-B (R 2 = 0.35, P = 0.019; and R 2 = 0.38, P = 0.017, respectively). In HCs, the cluster of right precentral/middle frontal gyrus/inferior frontal gyrus/inferior triangular gyrus showed a significant relationship with TMT-B (R 2 = 0.59, P = 0.010). No relationship was found between the susceptibility values with MoCA in the brain region in both two groups. CONCLUSION: Patients with T2DM presented declined cognitive assessments and elevated iron deposition in the striatum and frontal lobe, suggesting that executive function decline in T2DM might be associated with the cerebral iron burden and that changes in susceptibility values may represent a latent quantitative imaging marker for early assessment of cognitive decline in patients with T2DM.
PURPOSE: Brain iron accumulation has been suggested as a pathomechanism in patients with type 2 diabetes mellitus (T2DM) with cognitive impairment. This research aims to examine the total-brain pattern of iron accumulation in relation to executive function decline in patients with T2DM by voxel-based quantitative susceptibility mapping (QSM) analysis. MATERIALS AND METHODS: A total of 32 patients with T2DM and 34 age- and sex-matched healthy controls (HCs) were enrolled in this study. All participants underwent brain magnetic resonance examination, and 48 individuals underwent cognitive function assessments. Imaging data were collected with three-dimensional fast low-angle shot sequences to achieve magnitude as well as phase images. Using voxel-based QSM analysis, we compared the voxel-wise susceptibility values of the whole brain among groups and explored whether the susceptibility values had correlations with cognitive data. RESULTS: Among the 66 participants, cognitive function was estimated in 23 patients with T2DM (11 males and 12 females; average age, 64.65 ± 8.44 years) and 25 HCs (13 males and 12 females; average age, 61.20 ± 7.62 years). T2DM patients exhibited significantly (t = 4.288, P < 0.001) lower Montreal Cognitive Assessment (MoCA) scores [T2DM, 27 (27, 28); HCs, 29 (28, 29); normal standard ≥ 26)] and higher Trail-making Test (TMT)-A/TMT-B scores [71 (51, 100)/185 (149, 260)] than HCs [53 (36.5, 63.5)/150 (103, 172.5)] (Z = 2.612, P = 0.009; Z = 2.797, P = 0.005). Subjects with T2DM showed significantly higher susceptibility values than HCs in the caudate/putamen/pallidum, frontal inferior triangular gyrus, and precentral gyrus on the right hemisphere. In contrast (HC > T2DM), no region showed a significant difference in susceptibility values between the groups. The correlation analysis between susceptibility values and cognitive function scores was tested by voxel-based susceptibility value with sex and age as covariates. After multiple comparison correction, in T2DM patients, the left thalamus showed a significant relationship with TMT-A (R 2 = 0.53, P = 0.001). The right thalamus and left thalamus showed a significant relationship with TMT-B (R 2 = 0.35, P = 0.019; and R 2 = 0.38, P = 0.017, respectively). In HCs, the cluster of right precentral/middle frontal gyrus/inferior frontal gyrus/inferior triangular gyrus showed a significant relationship with TMT-B (R 2 = 0.59, P = 0.010). No relationship was found between the susceptibility values with MoCA in the brain region in both two groups. CONCLUSION: Patients with T2DM presented declined cognitive assessments and elevated iron deposition in the striatum and frontal lobe, suggesting that executive function decline in T2DM might be associated with the cerebral iron burden and that changes in susceptibility values may represent a latent quantitative imaging marker for early assessment of cognitive decline in patients with T2DM.
Authors: Ziad S Nasreddine; Natalie A Phillips; Valérie Bédirian; Simon Charbonneau; Victor Whitehead; Isabelle Collin; Jeffrey L Cummings; Howard Chertkow Journal: J Am Geriatr Soc Date: 2005-04 Impact factor: 5.562
Authors: David Bergeron; Kelsey Flynn; Louis Verret; Stéphane Poulin; Rémi W Bouchard; Christian Bocti; Tamàs Fülöp; Guy Lacombe; Serge Gauthier; Ziad Nasreddine; Robert Jr Laforce Journal: J Am Geriatr Soc Date: 2017-02-15 Impact factor: 5.562
Authors: L I Kozlova; E D Petrovskii; E G Verevkin; M E Mel'nikov; A A Savelov; M B Shtark Journal: Bull Exp Biol Med Date: 2019-11-28 Impact factor: 0.804
Authors: Maria Del C Valdés Hernández; Stuart Ritchie; Andreas Glatz; Mike Allerhand; Susana Muñoz Maniega; Alan J Gow; Natalie A Royle; Mark E Bastin; John M Starr; Ian J Deary; Joanna M Wardlaw Journal: Age (Dordr) Date: 2015-09-17
Authors: Sabrina K Syan; Max M Owens; Ben Goodman; Leonard H Epstein; David Meyre; Lawrence H Sweet; James MacKillop Journal: Neuroimage Clin Date: 2019-10-26 Impact factor: 4.881