Alzheimers prevention

[Todd Joye]

I have a patient in her early 50’s whose mother developed early onset Alzheimers in her mid-late 60’s and wants to do whatever she can to take care of her brain now.  Aside from that family link, she has mild depression, and mild hypertension. She doesn’t smoke, and exercises a few times a week, is not diabetic and is not obese. Does anyone have any recommendations for peptide therapy – Dihexa, Selank, Semax? What about NAD?

 

[William Curtis]

Dr.  Joye, Interesting suggestions on the peptides and NAD.

I suspect this question will stimulate a lot of discussion.

I put some relevant papers in the SSRPI group on zotero.org

https://www.zotero.org/groups/4586446/ssrpi/collections/R9CKWP7G

Russ Swerdlow tested a ketogenic diet on patients with AD. They improved as much or better than the best current meds. Some people think a ketogenic diet might prevent AD:

Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2018; 4(1):28–36.

Mary Newport gave her husband ketone ester. It dramatically relieved his AD. Some people think AD is like a diabetes of the brain and glucose is not utilized properly. Ketone esters make up for the fuel deficit.

Newport MT, VanItallie TB, Kashiwaya Y, King MT, Veech RL. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement. 2015; 11(1):99–103.

Soto-Mota A, Vansant H, Evans RD, Clarke K. Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regulatory Toxicology and Pharmacology. 2019; 109:104506.

This article on Dihexa discusses what is known about Dihexa and AD.

Dihexa_1.pdf.

This paper discusses a mouse model of Dihexa.

Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Brain Sci. 2021; 11(11):1487.

Two articles on Selank:

Filatova E, Kasian A, Kolomin T, et al. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. Frontiers in Pharmacology [Internet]. 2017 [cited 2022 Feb 13]; 8. Available from:

Volkova A, Shadrina M, Kolomin T, et al. Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Front Pharmacol. 2016; 7:31.

An article on Semax

Sciacca MFM, Naletova I, Giuffrida ML, Attanasio F. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. ACS Chem Neurosci [Internet]. American Chemical Society; 2022 [cited 2022 Feb 13]; .

You should look into plasmalogens.

Goodenowe DB, Cook LL, Liu J, et al. Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer’s disease and dementia. Journal of Lipid Research. Elsevier; 2007; 48(11):2485–2498.

Wood PL, Mankidy R, Ritchie S, et al. Circulating plasmalogen levels and Alzheimer Disease Assessment Scale–Cognitive scores in Alzheimer patients. J Psychiatry Neurosci. 2010; 35(1):59–62.

Senanayake V, Goodenowe DB. Plasmalogen deficiency and neuropathology in Alzheimer’s disease: Causation or coincidence? Alzheimers Dement (N Y). 2019; 5:524–532.

Dr. Bradshaw spoke on dementia at the NAD conference. Those videos should be available soon.

I hope this gives you some information to get started.

All the best,

Bill Curtis

[Todd Joye]

Thanks for those references Bill! I registered for the NAD Summit but had to juggle a couple other commitments that weekend and missed Dr Bradshaw’s talk – but did catch part of yours. Fortunately, I did also purchase the videos and look forward to diving into them.

[Elizabeth Yurth]

Agree with Bill Curtis on plasmalogens. Would run a prodrome scan but plasmalogens will be key. Beyond that need to optimize hormones and nutiretns of course and then we use IV cerebrolysin infusions which have excellent benefits with the caveat that they are hard to get and pricey but perhaps one of the most effective therapies. Be sure methyltransferase reserves are optimized with 3-5 grams of creatine, 5000mcg of methylcobalamin, B6 and MTHF. 2grams NAC for mitochondria and detox, acetyl l carnotine and ubiquinol or better yet if can afford-urolithin a.

Spermidine huge for brain health as well! but again pricey. But do a t least 1-2mg daily.  https://link.springer.com/article/10.1007/s00508-020-01758-y

https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.045750

 

Dr Yurth

[Todd Joye]

Thank you for your counsel Elizabeth. Don’t know how these pertinent medical history were left out of my inquiry, but she also has Factor V Leiden (on Eliquis) and a h/o HER2+, PR negative, weak positive ER breast cancer that was successfully treated with chemo and double mastectomy in 2015, now 6 years s/p treatment. As a result, she has concerns about estrogen replacement. Would that change any recommendations?

[Todd Joye]

Hi Bill, just a quick question.  On the Zotero links you posted, the Dihexa_1.pdf is not accessible/doesn’t open. Can you resend?

[William Curtis]

This is the file.

[Giovanni Silva]

April 22, 2022: The American Journal of Clinical Nutrition “Vitamin D and brain health: an observational and Mendelian randomization study”.

“Reduced plasma desmosterol-to-cholesterol ratio and longitudinal cognitive decline in Alzheimer’s disease”

The precursor of Vit. D is Desmosterol, a ROR gamma agonist that sits above Vit. D. Desmosterol is a key modulator of inflammation. Some studies show that a decrease in Desmosterol precedes Alzheimer’s.

[Kristelle Reyes]

Launch CME Experience here: https://earnc.me/teYIQw

[Caroline Snelwar]

Thank you Dr. Curtis for the resources,

We do implement many of your noted measures for our Alzheimer patients under Dale Bredersen’s protocols.

Has any one used DIHEXA and we wondered about dosing oral rather than topical? I see that the study references 2mg/kg/day but wondered in humans what dose is used.

Is there a strong concern for tumorigenesis and cancer progression with this particular peptide?

Thank you for this wonderful forum!

Kind Regards

Caroline

 

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