Elevated inflammatory markers in diabetes-related dementia

Abstract

Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia.1 In our previous study, we defined a dementia subgroup with characteristics predominantly associated with DM-related metabolic abnormalities.2 This type of dementia, showing neither cerebrovascular disease (CVD) on magnetic resonance imaging (MRI) nor parietotemporal hypoperfusion on single photon emission computed tomography (SPECT), was clinically characterized by old age, high hemoglobin A1c (HbA1c), long duration of diabetes, high frequency of insulin therapy, low frequency of apolipoprotein E4 (ApoE4) carriers, less severe medial temporal lobe atrophy, more impaired attention, less impaired word recall and slow progression of cognitive impairment. This dementia subgroup was referred to as “diabetes-related dementia”.2 However, the underlying pathophysiology remains unclear. In the present study, we tested the association between inflammatory markers and cognitive impairment in this type of dementia. Among 175 patients with clinical diagnosed probable or possible Alzheimer's disease (AD) and type 2 DM in our previous study,2 we compared plasma levels of cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hs-CRP) between 49 participants showing parietotemporal hypoperfusion on SPECT, but not showing CVD on MRI (AD pattern group), and 25 not showing parietotemporal hypoperfusion or CVD (non-AD pattern group). IL-6, TNF-α and hs-CRP were quantified with commercially available enzyme-linked immunoassays and nephrometry, respectively. Values were expressed as means ± standard deviation. Statistical analysis was carried out using Student's t-test, the χ2-test, analysis of covariance (ancova) and Spearman's rank correlation test. Table 1 shows comparisons of participant characteristics, and plasma cytokines and hs-CRP. The non-AD pattern group was significantly older, had higher HbA1c levels, longer duration of diabetes and higher frequency of insulin therapy than the AD pattern group. There were no significant differences in sex, Mini-Mental State examination (MMSE) score, education, duration of dementia, frequency of ApoE4 carrier, and total cholesterol and triglyceride levels. ancova, taking into account age and HbA1c as a covariate, showed that the non-AD pattern group showed significantly higher levels of IL-6, and a tendency toward higher TNF-α (P < 0.1) and hs-CRP (P < 0.1) compared with the AD pattern group. A significant inverse correlation between IL-6 levels and MMSE scores was found in the non-AD pattern group (correlation coefficient (r) = −0.441, P < 0.05), but not in the AD pattern group. Several studies have shown that systemic markers of inflammation are associated with cognitive decline in elderly subjects.3, 4 A recent study showed that higher IL-6 and TNF-α levels were associated with poorer cognitive ability in people with type 2 DM.5 The present results suggest a possible role for IL-6 in cognitive impairment in the non-AD pattern group. Although the mechanisms that link elevated inflammatory markers and cognitive decline remain unclear, future studies are required to determine whether amelioration of systemic inflammation might be considered to be treatment strategies for preventing or delaying cognitive decline of diabetes-related dementia. The authors state that they have no financial disclosures to declare.