Akio Kanai

Does cerebral small vessel disease predict future decline of cognitive function in elderly people with type 2 diabetes

AIMS We conducted a 3-year longitudinal study concerning an association between cognitive function and cerebral small vessel disease (SVD) seen on magnetic resonance imaging (MRI) in elderly type 2 diabetic patients. METHODS Four cognitive function tests--MMSE, word recall, Digit Symbol Substitution (DSS), and Stroop Color Word (Stroop)--were performed in 67 diabetic patients twice in 2006 and 2009. SVD was diagnosed as silent brain infarct (SBI) and white matter lesions (WMLs) according to MRI. RESULTS Number of SBI was significantly correlated with a decline in DSS and Stroop tests, while WMLs grade was only associated with it in DSS tests after adjustment for age, gender, education years, the presence of hypertension and dyslipidemia, and smoking. Severity of SVD at baseline was stronger associated with cognitive function after the 3-year follow-up than at baseline. WMLs progression was associated with more rapid decline of DSS tests compared to a group without progression. CONCLUSIONS SVD seen on MRI is a good marker for predicting future cognitive decline, and monitoring of treatment through the use of such markers is expected to maintain a good quality of life for elderly diabetic patients.

The effect of cigarette smoking on soluble adhesion molecules in middle-aged patients with Type 2 diabetes mellitus.

Aims To investigate the effect of smoking on soluble adhesion molecules in middle‐aged diabetic patients.

Glucose control levels, ischaemic brain lesions, and hyperinsulinaemia were associated with cognitive dysfunction in diabetic elderly

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Association between future events of brain infarction and soluble levels of intercellular adhesion molecule-1 and C-reactive protein in patients with type 2 diabetes mellitus

We investigated the influence of the reciprocal association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and intercellular adhesion molecule-1 (sICAM-1) on the risk of brain infarction in type 2 diabetic patients. One hundred seventy nine middle-aged and elderly diabetic patients without histories of cardiovascular events were followed up for an average of 8 years. Fourteen patients developed symptomatic brain infarction (BI) during follow-up. These patients had significantly higher blood pressure, longer duration of diabetes, silent brain infarction, microvascular complications such as macroalbuminuria, and higher creatinine, sICAM-1 and hs-CRP levels at baseline as compared with those without BI. A high risk of stroke was observed in patients with high levels of sICAM-1 (>260microg/L) and hs-CRP (>0.83mg/L) at baseline, respectively, and patients with high levels of both were more likely to develop BI. In addition, sICAM-1 levels were significantly correlated with systolic blood pressure and glycemic control index, whereas hs-CRP levels were correlated with fasting insulin levels, HDL-cholesterol, triglycerides, and uric acid. Consequently, sICAM-1 and hs-CRP levels were, respectively, reflected in different cardiovascular risk factors. This study suggests that both measurements of hs-CRP and sICAM-1 levels are useful as a predictor of future stroke in diabetic subjects.

Factors Associated with Cognitive Decline in Elderly Diabetics

Background/Aims: Although recent evidence has indicated that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia, few studies have prospectively observed this potential cognitive decline. In the current study, we performed cognitive assessments at baseline and after 3 years in the same patient group in an attempt to reveal the contributions of diabetes-related factors to the increased decline in cognitive function in elderly patients with T2DM. Methods: We recruited 55 consecutive T2DM patients with a Mini-Mental State Examination (MMSE) score ≧24 from the Diabetic Center at the Chubu Rosai Hospital. These patients ranged in age from 65 to 85 years. Cognitive and clinical assessments, including brain MRI, were performed at baseline and at the 3-year follow-up. Results: The higher plasma insulin and HbA1c levels observed at baseline were significantly associated with a worse cognitive performance at baseline and a more neurocognitive decline at the follow-up visit. Conclusion: The current prospective study suggests that higher insulin and glycohemoglobin levels may be associated with diabetes-related cognitive dysfunction.

Effect of renal impairment on cognitive function during a 3-year follow up in elderly patients with type 2 diabetes: Association with microinflammation

We investigated the effect of renal impairment on cognitive function during a 3‐year follow up in elderly type 2 diabetic patients, and an association with microinflammation.

Association of Soluble Adhesion Molecule and C-Reactive Protein Levels with Silent Brain Infarction in Patients with and Without Type 2 Diabetes

Silent brain infarction (SBI) is often detected on MR imaging, however the pathogenesis is still unclear. We aimed to investigate and compare the association of soluble adhesion molecules and C-reactive protein levels with the prevalence of SBI in patients with and without diabetes mellitus. We recruited 130 patients (mean age 59.6 +/- 7.6 yrs) with type 2 diabetes and 130 age- and sex-matched non-diabetic subjects. All subjects underwent head MRI to determine SBI. We measured levels of soluble intercellular adhesion molecule 1(sICAM-1), vascular cell adhesion molecule 1(sVCAM-1), and high sensitivity C-reactive protein (hs-CRP) and evaluated intima-media complex thickness (IMT) in common carotid arteries by ultrasound B-mode imaging. SBI was present in 36 (27.7%) of the diabetic patients and 31 ( 23.8%) of the non-diabetic subjects. Levels of sICAM-1, sVCAM-1 and IMT were all significantly higher in diabetic patients than in non-diabetic subjects, and were significantly increased in both subjects with SBI. IMT was only positively correlated with sVCAM-1 levels in diabetic and non-diabetic subjects. On the other hand, hs-CRP levels were not significantly different in both subjects with and without SBI. In addition, sICAM-1 levels were associated with a significantly higher relative risk for the prevalence of SBI in diabetic patients after multivariate adjustment. Our study suggests that the associations between endothelial dysfunction and presence of SBI may be stronger in diabetic patients than in nondiabetic subjects. In particular, sICAM-1 may play an important role for the pathogenesis of SBI in patients with diabetes mellitus.

Factors Associated with Brain Atrophy Estimated with Automatic Voxel- Based Morphometry of Structural Magnetic Resonance Images in Elderly Diabetic Patients: Impact of Albuminuria on Hippocampal Atrophy

Background: We investigated what factors were associated with brain atrophy in elderly patients with type 2 diabetes. Methods: We evaluated hippocampal and whole brain atrophy with automatic voxel-based morphometry of structural magnetic resonance image (MRI), voxel-based specific analysis regional analysis for Alzheimer’s disease (VSRAD), in 70 diabetic subjects and 35 non-diabetic subjects. Cognitive function tests – MMSE, word recall (immediate and delayed), Digit Symbol Substitution test (DSST), and Stroop Color Word (Stroop) test were performed. Cerebral small vessel disease (SVD) was diagnosed as silent brain infarct and white matter lesions (WMLs) according to MRI. Results: Significantly stronger hippocampal and whole brain atrophy were observed in diabetic patients than non-diabetic subjects. The levels of glycosylated hemoglobin A1c were significantly correlated with indices of hippocampal and whole brain atrophy. In diabetic subjects, hippocampal atrophy was independently associated with age, albuminuria, serum intercellular adhesion molecules -1 levels and lower diastolic blood pressure, while whole brain atrophy was associated with age and subcortical WMLs grade. Regarding an association between albuminuria and brain atrophy, significant hippocampal and whole brain atrophy were found in patients with albuminuria after adjusting for confounders. Hippocampal atrophy was independently associated with word recall and Stroop test after adjustment, while whole brain atrophy was also associated with word recall, DSST, and Stroop test, although the association weakened after adding degree of SVD to the variables. Conclusions: Albuminuria was an independent risk factor for brain atrophy, especially hippocampal atrophy, which was associated with cognitive impairment, suggesting that the management of albuminuria may prevent progression of brain atrophy resulting in cognitive decline. In addition, the usefulness of VSRAD to support diagnosis of cognitive decline associated with brain atrophy was shown in daily clinical setting.

Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD) in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR), albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.