Treatment and Prevention Strategies for Cognitive Function in PCa

[MateoBeach]

Treatment and Prevention strategies for cognitive function in men being treated for advanced prostate cancer. Mild cognitive impairment (“brain fog” chemo-brain”) is common and widely recognized in those being treated with ADT and androgen signaling drugs, as well as with taxane chemotherapy. I am highlighting 3 possible therapeutic strategies that may help ameliorate or improve treatment-caused cognitive impairment. One is a prescription. The other two are OTC supplements. These are, as always, on top of not instead of, optimal complete nutritional, good sleep hygiene, moderate to no alcohol intake, and exercise, lots of exercise both physical and mental. Be safe and well and treasure every day. Paul/MB

1) Estradiol Patches during ADT and ARSI therapies. Also effectively supports ADT by helping suppress the hypothalamic-piruitary-testicular axis (LHRH inhibition). Also alleviates the adverse side effects of ADT and castrate androgen levels, including hot flashes as well as MCI, depression and fatigue.

Typically 0.025 - 0.10 mg per day biweekly patches hile on ADT. Much higher doses can achieve castrate testosterone levels as a monotherapy per the PATCH trial. Did not increase adverse cardiovascular events as oral estrogens can (DES). Use the PATCH Trial results to convince your doctor(s).

2) Theracurmin. Theracurmin is a proprietary form of Curcumin that is micro-sized particles to provide much better bioavailability. There are several brands that license this from the Japanese company that makes it for non prescription supplements. Its effects on MCI are demonstrated in a RCT below. Another specialized (lipidated) form of bioavailable curcumin, called Longvida, has also demonstrated beneficial effects in MCI. Not sure which may be better of the two.

3) Magnesium-l-Threonate (MagT). This is a formulation of Magnesium supplementation that can cross the blood-brain-barrier and increase magnesium levels in the brain much better than other forms of magnesium supplementation. Soft evidence, mostly animal, is suggesting that it can improve memory and cognitive function. It also reduces neuro-inflammation such as that modulated by TNF-a, and protects against oxidative stress. It also appears to reduce chronic pain, reduce anxiety and improve sleep. There is one RCT in older humans with a Mag-T supplement linked last below. While the jury may still be out about the benefits in humans, it may be worth considering on a personal trial basis as I am doing now.

Neurocognitive impairment associated with traditional and novel androgen receptor signaling inhibitors ± androgen deprivation therapy: a pharmacovigilance study

nature.com/articles/s41391-...

pubmed.ncbi.nlm.nih.gov/374...

Estrogen/ Estradiol Supports and Protects Brain and Spinal Function

journals.physiology.org/doi...

Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial

pubmed.ncbi.nlm.nih.gov/292...

Evidence of Benefits to Mood and Working Memory from Lipidated Curcumin in Healthy Older People

pubmed.ncbi.nlm.nih.gov/325...

Enhancement of Learning and Memory by Elevating Brain Magnesium

sciencedirect.com/science/a...

Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α

pubmed.ncbi.nlm.nih.gov/240...

Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

ncbi.nlm.nih.gov/pmc/articl...

[marnieg46]

Paul a very helpful and informative post. Thank you.

From my experience it seems that impaired cognitive function, as a result of ADT and ARI's, is one of the side effects that is often lost because the other side effects are often so clear and decisive but the cognitive damage just creeps up. This is further compounded by the fact that many with prostate cancer are already approaching an age where, at least initially, reduced cognitive functioning can be passed off or overlooked because there's an expectation that with increased age some loss of acuity is 'normal' or to be expected.

What I have found is that, when the impairment is actually picked up, not just by personal acknowledgement but rather in the course of routine meeting/appointments and suggestions made for a geriatric assessment to rule out dementia or Alzheimer's you're faced with a difficult decision. A question of... basically what benefit would be gained by involving yet another specialist...which would bring the total to seven. To that mix, add in the possible detrimental effects on the person actually knowing that it's something more serious and then not able to laugh it off or explain it as just the side effects of drugs.

From a practical perspective options 2 and 3 that you've written about seem to be very doable for those not able to access a prescription or want to wander from the SOC path. You've given me some holiday research to do and no doubt I'll come back with questions for you. I guess one question that I do have is are the benefits helpful if you start late in the game? Guess I might find the answer once I read up some more.

I will be in touch with seasonal wishes but do want to take this opportunity to thank you for the ongoing excellent information and gems of wisdom you provide so generously to all who read on this forum and who seek a wider, well informed view of many of the aspects and challenges faced on this journey. Priceless.

[d3is4me in reply to marnieg46]

Marnie great reply I know i am suffering

[marnieg46 in reply to d3is4me]

Hi Ross. Thank you. It's a topic close to home unfortunately.

It's such an important aspect that Paul's written about. Not just the obvious fall out but I think for some the added fear of losing more independence over their life.

While every situation is different and the scale varies, I've found the struggle really is what precautions need to be taken to minimise the damage - personal, financial and interrelationship wise with other people who might not be aware of what's going on. And doing this without unnecessarily taking away personal freedoms where a stuff up isn't going to matter much one way or another. This coupled with long periods of high cognitive functioning cause confusion for all involved.

I guess you'd have to have an inkling that the combination of drugs you and Ron are on must take a toll eventually. What I've found more surprising, as we've discussed recently, is that the 3 mthly ADT which would hardly have rated a mention in prior times, now seems to 'knock him for six' for weeks. Perhaps accumulation.

I'm really sorry you feel life's a bit of a challenge lately. I think these special holiday times add a bit extra stress to everyday life and that also doesn't help. Maybe it's just a matter of one day at a time and not overthinking (as I tend to do 🙄).

Do keep in touch and I'll do likewise.

[cujoe]

MB, While continuing to attempt to decode the potentiate benefits vs risks of sauna/steam room use (think Heat Shock Protein activation) for PCa+, I came across this paper from the Journal of Applied Physiology that might be of interest to you. Being a few years older than you, I also am in the possession of an "aging brain", so likely could benefit from some metabolic assistance and HSP chaperoning.

Heat therapy: possible benefits for cognitive function and the aging brain, Journal of Applied Physiology, Review - Physiology of Thermal Therapy, 11 Dec 2020.

journals.physiology.org/doi...

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease, yet there are no disease-modifying treatments available and there is no cure. It is becoming apparent that metabolic and vascular conditions such as type 2 diabetes (T2D) and hypertension promote the development and accumulation of Alzheimer’s disease-related dementia pathologies. To this end, aerobic exercise, which is a common lifestyle intervention for both metabolic disease and hypertension, is shown to improve brain health during both healthy aging and dementia. However, noncompliance or other barriers to exercise response are common in exercise treatment paradigms. In addition, reduced intracellular proteostasis and mitochondrial function could contribute to the etiology of AD. Specifically, compromised chaperone systems [i.e., heat shock protein (HSP) systems] can contribute to protein aggregates (i.e., β-amyloid plaques and neurofibrillary tangles) and reduced mitochondrial quality control (i.e., mitophagy). Therefore, novel therapies that target whole body metabolism, the vasculature, and chaperone systems (like HSPs) are needed to effectively treat AD. This review focuses on the role of heat therapy in the treatment and prevention of AD. Heat therapy has been independently shown to reduce whole body insulin resistance, improve vascular function, activate interorgan cross talk via endocytic vesicles, and activate HSPs to improve mitochondrial function and proteostasis in a variety of tissues. Thus, heat therapy could offer immense clinical benefit to patients suffering from AD. Importantly, future studies in patients are needed to determine the safety and efficacy of heat therapy in preventing AD.

. . .

Summary

AD is the most common neurodegenerative disease, yet there are no disease-modifying treatments available and there is no cure. We believe that heat therapy can be of tremendous clinical benefit to patients with AD (Fig. 1). Specifically, we and others have shown that heat therapy prevents obesity and insulin resistance and restores target blood glucose and insulin levels—all risk factors associated with AD. Moreover, it is well established that heat therapy increases blood flow and vascular compliance, in addition to potentially increasing interorgan cross talk via EV transport/formation. Finally, we propose that HSPs induced via heat therapy are critical for proteostasis (protein aggregate degradation), mitochondrial function (mitophagy, mitochondrial respiratory capacity, and mitochondrial health), cross talk (stress sensing in distant organs such as the brain), and general cell health (inhibition of c-Jun and NF-κB signaling). Overall, emerging research indicates that heat and HSP induction show immense therapeutic potential in nearly all diseases with an inflammatory, proteostatic, and/or metabolic component—making heat therapy a logical and important research focus for the prevention of chronic disease.

Happy New Year - a few days early! May 2024 be a very healthy and happy year!

Best to you, J & K9 mb,

Ciao - Capt'n cujoe

[MateoBeach in reply to cujoe]

Very nice article and consideration Cap’n. Would justify a home sauna if I had a place to put one! As it is Johane and I take very hot baths to tolerance. Immersion accelerates heat transfer though sauna with steam very effective. I’m also considering alternating with cold water immersion “dipping” or a roll in the snow alternating with sauna or hot tub/bath. Johane goes into cold river after runs. Positive hormesis effects from that. Kind regards. MB