PROJECT SUMMARY/ ABSTRACT
Type 2 diabetes mellitus (T2DM) patients make up 90-95% of all diagnosed diabetes mellitus and show
serious cognitive and mood deficits that are associated with increased morbidity and mortality, poor self-care,
and decreased life quality. These deficits are linked to brain tissue changes, potentially resulting from impaired
blood brain barrier (BBB) function. However, it is unclear whether BBB function can be repaired in T2DM
adults, reducing impaired cognition and mood functions and early risks of dementia and Alzheimer’s disease.
The BBB restricts diffusion of microscopic objects (such as bacteria) and large (e.g., antibodies and many
drugs) or hydrophilic molecules (e.g., salt) from crossing into brain tissue and protects from harmful
substances. Although multiple methods, including positron emission tomography, single photon emission
computed tomography, and contrast-based magnetic resonance imaging (MRI) can examine BBB function,
they are either invasive or pose significant health risks on humans. Using non-invasive MRI based diffusion-
weighted pseudo-continuous arterial spin labeling (DW-pCASL), BBB function status can be examined, which
has been validated to examine BBB breakdown in pre-clinical and in pilot T2DM studies. Several pre-clinical
studies suggest the possibility for BBB function repair, including low-cost thiamine intervention. Thiamine is an
essential component for carbohydrate metabolism and adequate or higher levels promote aerobic metabolism.
In addition, reduced thiamine levels are shown contributing to impaired endothelial cell functions, leading to
BBB dysfunction, and higher doses improve endothelial functions. Although the majority of T2DM adults show
thiamine deficiency that may contribute to impaired BBB function, but it is unclear if the thiamine treatment can
improve BBB function. Therefore, using 52 T2DM adults with randomized clinical trial, the specific aims are to:
1) compare BBB function, using DW-pCASL, and blood serum BBB (S100ß levels) biomarkers in T2DM adults
with and without thiamine treatment and 2) examine cognition (Wide Range Assessment of Memory and
Learning 2 and Montreal Cognitive Assessment) and mood (Beck Depression Inventory II and Beck Anxiety
Inventory) between T2DM adults with thiamine treatment compared to T2DM adults without thiamine
treatment. In summary, low-cost thiamine treatment will be performed to assess whether impaired BBB
function and mood and cognition deficits are improved in T2DM adults. If successful, the information from this
clinical trial might serve as a novel and innovative treatment strategy to repair BBB function, affecting less
cognition and mood function, and hence better outcomes in T2DM adults. This R21 clinical trial study will
provide required data regarding the benefits of a low-cost thiamine intervention that could be implemented on a
large-scale clinical trial to repair BBB function, and thus, decrease early dementia and Alzheimer’s disease,
reduce morbidity and mortality, and increase quality of life in T2DM adults.