In type 1 and type 2 diabetes thiamine levels are deficient and kidney excretion greatly increased.

>Renal clearance of thiamine is increased by 8-fold in experimental model of diabetes. Interestingly, increased clearance was prevented by high-dose thiamine supplementation[26]. Thiamine renal clearance is also increased in subjects with T1DM (by 24-fold) and T2DM (by 16-fold)[24].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058733/

Part of the disease risk manifested in diabetes was also stated to be retained even after glucose regulation back to normal range - indicating that diabetes is not simply a blood sugar dysfunction and the disease mechanisms are not only manifested through it. One scientist I remember stated that two-thirds of the disease risk remains after blood glucose regulation and that this might be largely mitigated with agents such as thiamine and lutein.

Lutein is an interesting compound that negatively correlates to diabetes risk, but it also concentrates above serum levels in the brain, as well as skin and retina.

Lutein hyperaccumulates in brain -

https://pubmed.ncbi.nlm.nih.gov/24691400/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648219/

-DHA distribution also correlates with lutein. This suggests a natural tendency to accumulate these compounds together and that this is a functional thing. Lutein upregulates natural production of antioxidants in retinal tissue and might be doing that in the brain. There are associations of both DHA and Lutein to protection against Alzheimers / dementia.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259852/

- this is a negative result regarding DHA supplementation (DHA on its own, it may also be oxidised prior to consumption and this is known to reduce tissue distribution of DHA potentially leading to ineffective dosing. So the study may be worthless if there is not means to reduce DHA degradation in vitro or/and prior to consumption.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502665/

- this later study addresses this with higher dose but I believe does have connections to a supplier of DHA, full disclosure.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838628/

https://pubmed.ncbi.nlm.nih.gov/35745137/

https://pubmed.ncbi.nlm.nih.gov/22045492/

- lutein protects blood lipids, phospholipids and presumably lipoproteins from oxidation - thereby it should protect DHA from oxidation in the main carrier that transports it the brain, although it may act on different lipids rather than DHA, still of relevance to the oxidative stress and inflammatory signalling found in Alzheimers -

https://pubmed.ncbi.nlm.nih.gov/32088804/

Its a complicated picture - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648219/

>Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05). In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05).

- It seems reasonably to predict that non-oxidised DHA is superior at lower doses in delivery to the brain and that co-administration of DHA with lutein is potentially superior again, and that this may be beneficial in protecting the brain.

More on Lutein

https://www.researchgate.net/publication/6853199_Lutein_effect_on_retina_and_hippocampus_of_diabetic_mice

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223987/

https://www.frontiersin.org/articles/10.3389/fnut.2022.843512/full

https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170713

https://academic.oup.com/jn/article/151/3/615/6109668?login=false

Thiamine

Consequently thiamine was suggested as a way to reduce some of the residual risks such as peripheral polyneuropathy.

Remember when Alzheimers was referred to as 'Type 3 diabetes' due to insulin, glucose and metabolic dysfunction in the brain?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831864/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846521/

>Indeed, comparisons of immunocytochemical markers suggest that oxidative stress is more prevalent in AD than are plaques or tangles.8 Indeed, markers of oxidative stress in the urine of mice genetically engineered to make plaques precede plaque formation in the brain.9

- it isn't necessarily the plaques, but more the sub units that form into plaques that act as contributors, and there is a role for Tau as well, but they are just roles in something multi-factorial in origin.

>Glucose metabolism is always diminished in AD
>
>Extensive research has examined the relationship of cerebrospinal fluid (CSF) biomarkers of amyloid and tau and compared those to glucose metabolism, as measured by [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET).10 Reduced glucose metabolism occurs in AD long before the patient demonstrates significant clinical signs of AD. The regional changes in glucose metabolism are also highly correlated to changes in cognition. The correlation of changes to amyloid as measured by PET scan is very poor.11 The common explanation for these changes is that glucose metabolism as measured by [18F]FDG PET reflects synaptic activity, and since a loss of synapses accompanies AD, the loss of glucose use merely reflects the decline in synapses. This is likely true but also raises the possibility that reductions in glucose metabolism promote AD.

It seems to have overlapping aspects with the known types of diabetes.

If you have type 2 or 1 diabetes, you may have lower brain thiamine. In Alzheimers additional things could be happening in the brain that emulates low brain thiamine or dysfunction of thiamine pathways that could, like amyloid or tau, have a role in the disease, but maybe not always. Its still likely a multifactorial thing.