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.
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.
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 Aβ 42 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.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The ADNI investigators contributed to the design and implementation of ADNI and/or provided data. The ADNI list is available on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.