Type 2 diabetes mellitus and biomarkers of neurodegeneration - PubMed (original) (raw)
Type 2 diabetes mellitus and biomarkers of neurodegeneration
Chris Moran et al. Neurology. 2015.
Abstract
Objective: Our objective was to investigate whether type 2 diabetes mellitus (T2DM) influences neurodegeneration in a manner similar to Alzheimer disease (AD), by promoting brain β-amyloid (Aβ) or tau.
Methods: We studied the cross-sectional associations of T2DM with cortical thickness, brain Aβ load, and CSF levels of Aβ and tau in a sample of people from the Alzheimer's Disease Neuroimaging Initiative with diagnoses of AD dementia, mild cognitive impairment, and normal cognition. All (n=816) received MRI, and a subsample underwent brain amyloid imaging (n=102) and CSF Aβ and tau measurements (n=415). Analyses were performed across and within cognitive diagnostic strata.
Results: There were 124 people with T2DM (mean age 75.5 years) and 692 without T2DM (mean age 74.1 years). After adjusting for age, sex, total intracranial volume, APO ε4 status, and cognitive diagnosis, T2DM was associated with lower bilateral frontal and parietal cortical thickness (mL) (β=-0.03, p=0.01). T2DM was not associated with 11C Pittsburgh compound B standardized uptake value ratio (AU) in any brain region or with CSF Aβ42 levels (pg/mL). T2DM was associated with greater CSF total tau (pg/mL) (β=16.06, p=0.04) and phosphorylated tau (β=5.84, p=0.02). The association between T2DM and cortical thickness was attenuated by 15% by the inclusion of phosphorylated tau.
Conclusions: T2DM may promote neurodegeneration independent of AD dementia diagnosis, and its effect may be driven by tau phosphorylation. The mechanisms through which T2DM may promote tau phosphorylation deserve further study.
© 2015 American Academy of Neurology.
Figures
Figure 1. Association of T2DM with cortical thickness (n = 816)
(A) Association of T2DM with cortical thickness stratified by cognitive diagnosis. Adjusted for age, sex, total intracranial volume, and APO ε4 status. (B–D) Regions of cortical thinning associated with T2DM. Adjusted for age, sex, total intracranial volume, APO ε4 status, and cognitive diagnosis. (B) Left hemisphere: lateral view. (C) Right hemisphere: medial view. (D) Right hemisphere: lateral view. Regions: yellow = subcentral gyrus and sulcus; red = rectus gyrus; orange = inferior precentral sulcus; pink = front and middle sulcus; blue = inferior parietal gyrus. AD = Alzheimer disease dementia; MCI = mild cognitive impairment; T2DM = type 2 diabetes mellitus.
Figure 2. Regional associations of T2DM with Pittsburgh compound B SUVR
Adjusted for age, sex, cerebellum PiB uptake, APO ε4 status, and cognitive diagnosis. Normal control: n = 19, T2DM n = 6; MCI: n = 64, T2DM n = 11; AD: n = 19, T2DM n = 2. AD = Alzheimer disease dementia; MCI = mild cognitive impairment; SUVR = standardized uptake value ratio; T2DM = type 2 diabetes mellitus.
Figure 3. T2DM and CSF biomarker levels
Adjusted for age, sex, and APO ε4 status. Normal control: n = 114, T2DM n = 17; MCI: n = 199, T2DM n = 25; AD: n = 102, T2DM n = 14. AD = Alzheimer disease dementia; MCI = mild cognitive impairment; T2DM = type 2 diabetes mellitus.
References
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