I wish to open a discussion regarding the increased risk of late-onset Alzheimer's disease (LOAD) in those patients with pre-existing type 2 diabetes mellitus (T2DM).
I am contemplating writing a review on this topic since I found so many abnormal remodeling changes to the neurovascular unit in the db/db female model of obesity, insulin resisitance and T2DM recently reported in the literature.
Any and all questions and thoughts will be appreciated during this open discussion.
I hypothesize that the neurovascular unit (NVU) loss of barrier integrity is at the very core of the impaired cerebral blood flow (CBF) and neuronal synaptic dysfunction and loss with neurodegenation and atrophy found in T2DM and LOAD during the neuropathologic studies post mortem and in preclincal animal models of both T2DM and LOAD .
Any and all thoughts recommendations and findings will be greatly appreciated over the coming weeks and months.
Sincerely,
M.R. (Pete) Hayden, MD
I thought I would add a quote by Geert Jan Biessels from his commentary in Diabetes Care 2013:
Brain MRI Correlates of Cognitive Dysfunction in Type 2 Diabetes: The Needle Recovered From the Haystack? Geert Jan Biessels, MD, PHD⇑
Diabetes Care 2013 Dec; 36(12): 3855-3856.https://doi.org/10.2337/dc13-1501
"Importantly, in most cases Alzheimer-type and vascular pathologies co-occur (6). These mixed pathologies evolve on a background of aging-related changes in the brain. The total burden of cerebral pathologies, in interaction with structural and functional compensatory processes, also referred to as brain reserve or cognitive reserve (7), determine when cognitive dysfunction becomes clinically manifest. Where does diabetes come into this picture? It is certainly a challenge to pick up diabetes-related processes among these other pathological processes and the innate interindividual variation in brain structure and cognitive performance."
" The risk of dementia is increased by approximately 50% in people with type 2 diabetes (1,2). Assuming a prevalence of type 2 diabetes of approximately 15–25% in people aged over 65 years (3), this translates into a diabetes attributable risk of dementia of 7–11% at the population level"
Biessels further states:
" This understanding starts by acknowledging that diabetes is a risk factor rather than a cause for dementia: Diabetes by itself is neither sufficient nor required for dementia to develop. Therefore, the increased dementia risk in diabetes is most likely to be due to added or synergistic effects of processes related to diabetes and its comorbidities on top of other more generic, causative mechanisms for dementia."
I hypothesize, that while T2DM may be neither be required or sufficient for the development of dementia i.e. LOAD that because it damages the Neurovascular Unit and results in barrier dysfunction with leakage that it may certainly contribute to the development of age-related LOAD by allowing peripheral neurotoxins to be exposed to neurons, which could result in in syapse dysfunction and eventual loss with even neurodegeneration over time.
Also we know that in the db/db diabetic models there is brain atrophy at 26 weeks according to
Ramos-Rodriguez JJ
Ramos-Rodriguez JJ , Ortiz O, Jimenez-Palomares M, Kay KR , Berrocoso E, Murillo-Carretero MI, Perdomo G, Spires-Jones T, Cozar-Castellano I, Lechuga-Sancho AM, Garcia-Alloza M: Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice. Psychoneuroendocrinology (2013) 38, 2462—2475. doi: 10.1016/j.psyneuen.2013.05.010.
Plus we also know that in humans with T2DM there is brain atrophy by MRI studies:
Diabetes Care. 2013 Dec;36(12):4036-42. doi: 10.2337/dc13-0143. Epub 2013 Aug 12.
Brain atrophy in type 2 diabetes: regional distribution and influence on cognition.
Moran C1, Phan TG, Chen J,
Please feel free to chime in with questions and your thoughts as we look forward to having many invoved in this discussion.
pete hayden
Please see my preprint on this topic and provide any of your thoughts:
doi:10.20944/preprints201907.0265.v1
This preprint is now being processed for a new title as follows for Journal neuroglia in brain science with many revised figure images and text:
Type 2 Diabetes Mellitus Increases the RISK of Late-Onset Alzheimer's Disease: Remodeling of the Neurovascular Unit and Diabetic Gliopathy
I decided to enter the terms and focus on the Neurovascular Unit and Diabetic Gliopathy because so many ultrastructural remodeling changes were observed in the NERUOGLIA in addition to the vascular mural cells (the endothelium and pericyte). Please feel free to comment on your thoughts and ideas. Preprint should be available soon.
6 September 2019
With gratitude,
Melvin R Hayden
pete
Attached please find the final publication that can also be found In Brain Sciences: Article Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Al...
Article Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Al...
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Pharmaceuticals
- Drugs