Conventional MR imaging in Alzheimer disease (AD) patients have been challenging, especially in the early stage. Advanced diffusion techniques such as diffusion kurtosis imaging (DKI) have been shown to be sensitive to the micro-structure changes in the cerebral regions in AD patients ^[1] . AD concomitant with hyperglycemia is commonly observed during clinical work, and it was known that AD and disorder of glucose metabolism are related ^[2,3] .However, the factor of glucose level in AD patients have not yet been taken into consideration in the past studies, which might be of clinical significance in learning the AD progression. In this work, DKI is used to probe the likely effects of elevated glucose level in the white matter microstructure of AD patients.Three groups of participants were selected in this study: 1) fifteen AD patients with hyperglycemia; 2) fifteen AD patients without hyperglycemia; 3) fifteen age- and sex-matched healthy controls. AD patients who showed a glucose level higher than 6.11 mmol/L at the time of the scan were defined as hyperglycemia group. All the participants completed conventional MR and DKI scan on a 3.0T MRI system (GE Signa HDXT 3.0T MRI). DKI acquisitions consisted of 30 directions and three b values and the total scan time for full brain coverage was about 7 minutes. The bilateral MK values, Ka values, Kr values, MD values, Da values, Dr values and FA values of the frontal WM, parietal WM, occipital WM, temporal WM, splenium of the corpus callosum, genu of the corpus callosum, trunk of the corpus callosum, anterior limb of the internal capsule, posterior limb of the internal capsule, external capsule and hemispherium cerebelli were measured. One-Way ANOVA test was used to compare the mean values of different DKI metrics in all the identified ROIs in the two AD groups to the control group. Due to the large number of ROIs and metrics involved, any measurement for a given ROI and a given DKI metric that exhibited statistically significant difference as compared to control (P<0.05) was taken as one abnormal count. Also, the glucose levels of all AD patients were measured and correlated with their MMSE score using Spearman analysis.Fig.1 illustrates an example of the bilateral ROI selection on the MK map. Overall, out of a total of 140 measurements (# of metrics # of ROIs) made, 38 abnormal measurements were observed in the hyperglycemia group whereas only 18 abnormal measurements were observed in the non-hyperglycemia group, as compared to the control group (Fig.2). A comparison of the MK measurement in right frontal WM in the three groups is shown in Fig.3, which indicates the abnormal measurement in the hyperglycemia group as compared to the non-hyperglycemia group. Correlation between measured blood glucose levels and MMSE scores for all the enrolled AD patients is plotted and shown in Fig.4. It was seen that a strong negative correlation is observed (r= -0.732, P=0.001), indicating that the glucose level is strongly associated with the severity of AD. (Specifically, in the hyperglycemia AD group, the mean value of FA of bilateral frontal, left parietal WM, bilateral trunk of the corpus callosum, genu of the corpus callosum, left external capsule, MK of bilateral frontal, occipital, temporal WM, trunk of the corpus callosum, genu of the corpus callosum, external capsule, Kr of left parietal, left occipital, bilateral temporal WM, left trunk of the corpus callosum, left external capsule, Ka of right occipital, right temporal WM, bilateral anterior limb of the internal capsule decreased; whereas MD of left frontal, right parietal WM, Da of left frontal WM, bilateral hemispherium cerebelli, Dr of bilateral frontal, parietal, temporal WM increased.)Elevated glucose level has been reported be associated with higher severe level of AD, as also observed in the MMSE scores of patient cohort in this study. As elevated glucose level may also induce white matter damage, sub-grouping of AD patients according to the glucose level may further clarify the pathological changes related to AD. In this preliminary study, DKI in white matter has been demonstrated to be sensitive for the identification of structure changes in AD patients. Future research may focus on the specific DKI metric and cerebral region for for assessing white matter integrity in AD patients, while isolating the effects of glucose level disorder.