The Alzheimer’s Solution Revolution Podcast

Episode #22—Where We Left OffI’ll begin this episode by sharing an excerpt of the primary outcome from study #1 that I reviewed in part #1—#22—of this two part episode series.In that study, the authors found “a positive association between OC [plasma osteocalcin levels] and working memory capacity, executive functioning and global cognition scores.”Study #2—ExcerptThe authors of study #2 remarked “we observed that in both older adults with osteopenia and older adults with AD [Alzheimer’s disease] as compared to cognitively normal participants, BMD [bone mass density] values were lower and were associated with the severity of cognitive impairments.”And, "that BMD could identify AD participants with high accuracy”.Study #3 —ExcerptBone loss biomarkers were analyzed, and a key DEXA scan (dual-energy X-ray ) finding from the study revealed that: a lower bone mineral density is closely associated with early-stage AD in male patients.Study #4—ExcerptIn the review of study #4 of this two-part episode series, analysis of data drawn from 3,651 participants from a sub-study of the  Rotterdam Study found that the participants that had a lower BMD [bone mineral density] had a twofold higher risk over those with a higher BMD of developing dementia.Lastly, in episode #22, I quoted the lead author of the 2016 study, Christine Dengler-Crish, who stated “Measurement of bone density, which is routinely performed in the clinic, could serve as a useful biomarker for assessing AD risk in our aging population.”Gut-Bone-Brain Axis—ExcerptA significant body of research that has amassed over the past 20 years and more, and several key and recent studies have shown that the gut microbiota and the short-chain fatty acids (SCFAs), such as butyrate that are metabolized from fiber (resistant starches) fermentation play a role in regulating bone homeostasis (bone resorption and formation).A very recent study concluded that “Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients’ BMD (bone mass density) ​​and clinical findings.”Estrogen in the Bone-Brain Axis—ExcerptEstrogen—RANKL-RANK PathwayI’ll now close out this episode with a review of a couple of key risk factors linked to estrogen, and how it all fits into the bone-brain axis.A key pathway in which estrogen modulates bone remodeling is represented by a key regulatory factor in this bone remodeling phenomena—the receptor activator of Nf-kB—or its acronym—RANK.Estrogen is a critical yin regulator of inflammation associated with osteoporosis and many other health conditions in a women’s body and brain.Estrogen’s regulatory effect on inflammation—a yin force— counters and naturally buffers the inflammation pathway of RANKL and RANK—the yang element in this duality.Tune in to hear the rest of the details and episode!Thanks, and God Bless!Ralph Sanchez, MTCM, CNS, D.HomBrainDefend® www.TheAlzheimersSolution.com https://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchez https://www.instagram.com/alzheimers_solution

Hello once again!This is your host Ralph Sanchez, and welcome to episode #22 and indeed, it has been much too long between this episode and the last one.I have been busy with new book projects on the key underlying risk factors for late-onset Alzheimer’s disease that are unique to women.I’ll have an announcement on when those books will be available here soon, and frankly, I'm looking forward to doing so.And on that note, I have in store for you another special episode today in which I’ll present the evidence and the rationale for the bone-heart-brain axis as it pertains to an increased risk for dementia and late-onset Alzheimer’s disease (LOAD), and why age-related bone loss may be an indicator of an increased risk for LOAD.Bone is an endocrine organSeveral key studies over the past 15 to 20 years have demonstrated that the human skeleton is an endocrine organ that bidirectionally communicates with our brain and our gut and other organs. Normally, one may think of typical endocrine organs such as the pancreas, thyroid or pituitary gland which produce and release hormones that regulate a myriad of functions in the body and brain.Well, the same can be said for bone, which secretes the hormones—FGF23 (Fibroblast growth factor-23) and osteocalcin—a peptide hormone.So let's dive right in to that osteocalcin overview.Osteocalcin—Heart and Brain HealthTo begin with, a seminal study published in 2007 by Dr. Gerard Karsenty, has set in motion numerous studies since which have expanded on these endocrine and metabolic linkages between a form of osteocalcin—uncarboxylated osteocalcin (ucOC)—and other organs.Indeed, bone cells (osteoblasts) secrete a form of a bone protein/hormone—osteocalcin (and others)—which is normally associated with the maintenance of bone mass, and it also functions as a key protein/hormone in the crosstalk and regulation of physiological pathways between bone A modified form of osteocalcin, uncarboxylated osteocalcin (ucOC), easily crosses the blood brain barrier, and it has been shown to an essential hormone in fetal brain development, and in the regulation of mood and cognition throughout life.Uncarboxylated osteocalcin that is associated with insulin resistance and cardiometabolic disease (metabolic syndrome, type 2 diabetes).Uncarboxlated osteocalcin in turn regulates insulin secretion in pancreatic islet cells which underlies the regulation of glucose homeostasis by bone.Thus, this bone-insulin dynamic is termed the bone-pancreas endocrine loop.In a collaborative research effort and study published in 2017, Dr. Eric R. Kandel, a Nobel laureate (Nobel Prize for Physiology or Medicine in 2000)  and senior researcher at Columbia University / Howard Hughes Medical Institute, and Dr. Karsenty, reported on a key hippocampal receptor— Gpr-158—that binds with osteocalcin and mediates hippocampal memory formation.The study also reported another significant finding with regard to the benefit of how osteocalcin mediated “a molecular pathway critical for hippocampal-dependent memory” by stimulating brain-derived neurotrophic factor (BDNF) transport to the synapses of hippocampus.So much more with regard to the role of osteocalcin and uncarboxylated in part 1 of this bone-heart-brain axis episode, so please listen in for the rest of the story.Episode #2 of the Bone-Heart-Brain Axis will be available soon so please look for it as it will include additional insights into this fascinating and important research and science.God bless and goodbye.BrainDefend®Ralph Sanchez, MTCM, CNS, D.Hom.https://www.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolution/https://www.linkedin.com/in/ralph-sanchez/https://www.instagram.com/alz

Welcome! This is your host Ralph Sanchez, and this is episode #21, I am expanding on the last episode, #20, titled: “Estrogen Deficiency and Cardiometabolic Disease Underlies a Woman's Greater Risk for Alzheimer's Disease”. This episode—part two of this two-part episode series—on the linkages between perimenopausal and postmenopausal estrogen declines in women and the risk for age-related disorders— will focus primarily on three types of estrogen:Endogenous estrogen (the kind you make).Estrogen replacement therapies (the kind you take), andPhytoestrogens (the kind you eat and supplement with),and what they potentially represent in a woman’s risk for dementia and late-onset Alzheimer's disease (LOAD). The role of  endogenous estrogen is not often inserted into the discussion with regard to a woman’s risk for LOAD and it may be an important risk factor to weigh into a risk evaluation. Note that today’s overview on the estrogen a woman naturally produces throughout her reproductive lifespan—endogenous estrogen—was not part of a previous episode, # 10, that focused on the importance of estrogen replacement therapy in women at midlife. Plus, I’ll revisit estrogen replacement therapy (ERT) and some very important and more recent studies findings on that topic to be aware of, and how plant estrogens, or phytoestrogens, may substitute for ERT. Since this will be a lengthy and dense overview on all of this here today, this summary will be a very abbreviated review of what I covered. First, I’ll reiterate that the discussion and overview on postmenopausal estrogen deficiency as a risk factor for dementia and LOAD should not be a compartmentalized overview on estrogen’s role solely on neurological health. As I detailed in the last episode, the role of estrogen in cardiometabolic health is a significant component that connects a woman’s vascular health, blood flow to the brain and atherosclerosis, in the risk for brain lesions known as white matter hyperintensities (WMHs). And the brain damage associated with said brain lesions (WMHs) are a significant biomarker linked to the risk for cerebrovascular disease and stroke, vascular dementia, and LOAD. Uncontrolled hypertension and atherosclerotic vascular disease restrict blood flow to the brain, and the vital nutrients and oxygen needed to fuel brain function. Please listen in to episode #19 here in which I leverage recent studies on Viagra to make a point about several structure and function aspects of vascular health in aging individuals—both women and men—that are vital and modifiable risk factors for LOAD and vascular dementia. Estrogen Exposure Throughout a Woman’s Lifetime For decades, the research centered around the role of estrogen and estrogen replacement therapy in the risk for late-onset Alzheimer's disease (LOAD) has yielded conflicting results that ranged from:harmful, tono benefit to,protective. In the last episode I explained why there is the seemingly conflicting outcomes that are associated with ERT, so please do listen in to that episode, #20. Regardless, the preponderance of that research on estrogen therapy in the potential risk for LOAD has dealt with exogenous estrogen therapies. However, there is another significant group of studies that must also be noted, and those are the ones that examined the link between the length of a woman’s reproductive years and the endogenous estrogen exposure during those years. Endogenous Estrogen Yes, there is another rich world of estrogen studies that have investigated the lifetime exposure to a woman’s endogenously produced estrogen on cognitive health and the

Welcome!This is your host Ralph Sanchez, and this is episode #20 here at The Alzheimer's Solution Revolution podcast channel. Today we are expanding on and diving a little deeper into two primary risk factors associated with an increased risk for dementia and late-onset Alzheimer's disease (LOAD) in women—cardiometabolic disease and postmenopausal estrogen deficiency in women. In my book, and in episode #10 here on this channel, I covered the critical role that estrogen plays in glucose metabolism and its role in glucose hypometabolism. In that episode I explain why glucose hypometabolism in the brain represents a neuroenergetic abnormality and risk factor for Alzheimer’s disease in aging individuals and how it pertains to postmenopausal women. However, glucose hypometabolism is not the only metabolic derangement that links low estrogen levels to the higher incidence for LOAD in women. The metabolic alterations related to type 2 diabetes, insulin resistance and cardiovascular disease is also linked to falling estrogen levels in perimenopause and postmenopause, which poses a significant risk for dementia and LOAD in women. And if you are not aware of it, my book—The Diabetic Brain in Alzheimer's Disease— details the multifactorial role of cardiometabolic disease as a primary risk factor for vascular dementia and late-onset Alzheimer's disease (LOAD). Indeed, in this episode—part 1 of this two-part episode series— we'll review the compelling research that describes pertinent and critical details with regard to the linkages between decreased estrogen levels after menopause and the increased risk for cardiometabolic disease in women. In fact, apart from postmenopausal estrogen deficiency as a risk factor for LOAD,  cardiometabolic disease is also a very significant risk factor associated with a woman's risk for vascular dementia and LOAD. Regardless, the point today is that steep declines in estrogen in postmenopausal women is strongly associated with the risk for cardiometabolic disease and LOAD, and both factors ARE modifiable. Cardiometabolic disease The alarming rates of cardiometabolic disease worldwide and here in the U.S. (detailed in the podcast) There also sex differences in the prevalence T2D and CVD across a lifespan. The global prevalence of T2D and CVD before midlife is slightly higher in men compared to women. However, there are regional and ethnic differences, and as men and women age, the prevalence of T2D and CVD (cardiometabolic disease) is markedly skewed toward a greater risk for both disease trajectories in women. Before menopause, estrogen exerts a protective effect against CVD and T2D, whereas in postmenopausal women lower levels of estrogen and the loss of estrogen receptors leads to a precipitous decline in the protection against CVD and T2D in postmenopausal women. And a number studies over the past years have found that compared to men, postmenopausal women have higher rates of cardiovascular complications associated with T2D. Those cardiovascular complications include coronary heart disease or atherosclerotic cardiovascular disease, heart failure and stroke, and women have a higher mortality and worse prognosis after acute cardiovascular events. It is also estimated that in women, over the next 3 to 4 decades (2025 to 2060), the prevalence of cardiometabolic disease and the complications just mentioned will continue to outpace men. And again, to clarify the term cardiometabolic for those that are not familiar with it, it refers to metabolic health derangements that are linked to chroni

Summary Hello and welcome to episode #19! This is Ralph Sanchez and today I’ll be talking the outcomes of two recent studies that investigated the potential use of Viagra and Cialis in the risk reduction for late-onset Alzheimer’s disease (LOAD). I was in part inspired to provide an overview on these two recent studies as they are cautionary tales on how many studies do not include the interrelated factors that are essential in arriving to an integrated assessment and analysis that serves their very premise— which is, does this or that work in a potential solution to something else? Does Viagra or Cialis offer any proposed solution to the risk for LOAD and dementia? Well today, I’ll be adding a great deal of information—the missing pieces to the puzzle as it were—with regard the pathways by which Viagra and Cialis may or may not work, and many other complimentary or natural alternatives that play a similar role in maintaining and optimizing a healthy cardiovascular and cerebrovascular system. First, let me provide a little insight as to the molecular pathways in which drugs like Viagra and Cialis function, and why they may be considered as repurposed drug candidates for the treatment or in the risk reduction for LOAD. Viagra (sildenafil) and Cialis (tadalafil) are Phosphodiesterase-5 inhibitors (PDE5is) which fall into a class of drugs that are normally prescribed to men to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). PDE5is can have a profound effect on cardiovascular health and PDE5is mediate their benefits by inhibiting the breakdown of a molecule, cyclic GMP (cyclic 3′,5′ guanosine monophosphate). Cyclic GMP (cGMP) is an intracellular and second messenger molecule that modulates many downstream pathways, including significant effects in vasorelaxation—the ability of your blood vessels to dilate and expand as needed. The vascular effect that is enabled by PDE5i-induced vasodilation is a pivotal pathway in vascular homeostasis and a healthy heart-brain axis. And that vasodilation effect is how PDE5is improve and treat ED. There is a lot more to that vasodilation benefit mediated by PDE5i therapy  which I’ll get to here soon. So on to a brief description of the two recent studies on Viagra and Cialis, and so much more that was not included in those studies that will provide a crucial insight into how you can improve your vascular health and reduce your risk for LOAD. NIH StudiesFirst, a recent (2021)National Institutes of Health (NIH) funded study reported a risk reduction benefit of 69% for Alzheimer's disease (AD) in users of Viagra (Sildenafil). The analysis simply compared Viagra users to those who did not take it, and the study was focused on a screen of drugs that could potentially be repurposed in the risk reduction for AD in aging individuals. In a similar and second NIH funded study published this year (2022) titled— Drug Repurposing for Effective Alzheimer’s Medicines—(DREAM), the NIH analyzed data from Medicare beneficiaries that were treated with Viagra and Cialis. The NIH team compared people with pulmonary arterial hypertension (PAH) treated with Viagra and Cialis over those with PAH on another class of drugs (endothelin receptor antagonists) used to treat pulmonary hypertension. And note that PAH is a term that refers to high blood pressure in the blood vessels leading from the heart to the lungs Yes, PDE5is are also prescribed to patients to reduce blood pressure in PAH, and off-label use of PDE5 inhibitors (PDE5is) is used to treat cardiovascular diseases, Raynaud’s disease and women with female sexual arousal disorder.

Summary Welcome! This is Ralph Sanchez and today I’ll be expanding on the last two episodes—#16 & #17—in this special brain detoxification series. This is the third or part three in that series. In our last two brain detoxification episodes I described the pathways of beta-amyloid and tau protein transport and clearance from the brain, and in their degradation in the liver in what I describe as the liver-brain axis in Alzheimer’s disease. Today I’ll provide an overview on two related and crucial mechanisms of clearing debris, eliminating pathogens and neurotoxic proteins within the neuron and brain—namely autophagy and a complimentary proteasome degradation pathway. AutophagyWe’ll begin with autophagy which falters in aging and is significantly impaired in many age-related diseases such as cancer, cardiovascular disease, diabetes and neurodegenerative diseases such as Alzheimer's. These age-related diseases directly impact cellular protein turnover and disposal which is largely dependent on autophagy and a proteasomal degradation pathway, termed the ubiquitin-proteasome pathway. To keep this overview as simple as possible in light of the fact that all three forms of the autophagic machinery (macroautophagy, microautophagy, and chaperone-mediated autophagy ) and related pathways are very complex, I will for the most part only be describing here the role of macroautophagy with regard to the autophagy-lysosome pathway in waste recycling, removal and clearance. Macroautophagy is the most studied and described type of autophagy and it is the very same one that most educators speak of when describing the role of dysfunctional autophagy in the risk for AD. Now an important focus of today’s overview on autophagy is that it serves as an intracellular clearance mechanism of potentially toxic proteins such as beta-amyloid and tau protein that disrupt neuronal function and the integrity of our cognitive function in aging IF they are not appropriately turned over and degraded as needed. Autophagy also mediates the degradation of pathogens (e.g., viruses, bacteria), the removal of damaged cellular organelles like the mitochondria, and the cellular removal and recycling of proteins derived from the degradation of these targets for a nutrient and energy supply. The recycling of proteins and cellular organelles is a component in the regeneration of new proteins that serve as functional and structural substrates—e.g., cellular membranes and new organelles. Indeed, autophagy is a vital mechanism in cellular homeostasis throughout our healthspan. If your brain detoxification pathways are at their best, your odds of preventing dementia and living younger, longer are vastly improved. Now much of the public awareness with regard to the role of beta-amyloid in the brain revolves around the notion that beta-amyloid protein eventually forms plaque—outside the neuron—in the extracellular environment. And to that point, in the first episode (#16) of this brain detoxification series that focused on the transport and removal of beta-amyloid and tau protein from the brain, I gave an overview on the presence of beta-amyloid and tau protein in the extracellular fluid—the interstitial fluid—that is then funneled into the glymphatic system or transported across the blood brain barrier for removal from the brain. Additionally, the amyloid precursor protein (APP) that traverses the membranes of the neuron and generates the very beta-amyloid peptides that can eventually aggregate into deposits in the extracellular environment is also present on membranes within the neuron. APP is also present on mitochondrial membranes and the membranes of other intracellular organelles (e.g./ endoplas

Summary Hello and welcome to episode #17!This is Ralph Sanchez and today I’ll be expanding on the first episode’s overview with regard to beta-amyloid and tau protein clearance and detoxification.If you did not catch that episode (#16), I provided an in-depth overview on the role of the blood brain barrier (BBB) and the glymphatic system in clearing and transporting toxic beta-amyloid and tau protein from the brain.In today’s episode, I’ll review the emerging science and research with regard to the brain-liver axis in beta-amyloid clearance and metabolism, and how the gut fits into that, and a little on tau protein too.Now, the peripheral metabolism of beta-amyloid in the body is a very complex overview, however, I will cover two important organs that are associated with the origin and degradation of beta-amyloid in the body—the gut and liver.And, I will provide key features about that to illustrate what I term—the gut-brain-liver axis in late-onset Alzheimer’s disease (LOAD).First, there are three points I will make here with regard to the gut-brain axis, and its potential role for a healthy brain, or for neurological disease such as Alzheimer’s and Parkinson’s disease.First, the gut is potentially a powerful vector for proinflammatory cascades that induce neuroinflammation responses. Secondly, alteration of the gut barrier integrity leads to similar loss of the blood brain barrier integrity, And lastly, the generation of beta-amyloid proteins produced by bacteria in the gut.Yes, certain gut bacteria have been identified as specific beta-amyloid peptide producers linked to a beta-amyloid burden in the brain.Now note the latter point I just made about gut-derived beta-amyloid-like peptides (proteins) generated by gut microbiota which I will elaborate on more here soon.Nevertheless, the role gut-derived beta-amyloid-like proteins has in recent years been identified as drivers of neuroinflammation, AND amyloid and tau protein aggregation and deposition in the brain.Of course, pro-inflammatory pathways are driven by a host of physiological and pathological mediators that includes the gut, and numerous chronic diseases such heart disease and diabetes (cardiometabolic disease) which is well-described in the research literature. Gut-Brain Axis in Neuroinflammation The role of the gut-brain axis is a significant factor in the risk for numerous health disorders throughout life, and it can have substantial implications on your body-brain health as you age.Numerous studies that have examined the role of gut health disorders such as small intestine bacterial overgrowth or dybiosis to the detriment of brain health and the risk for cognitive decline and dementia have been accruing now for many years.BTW, for those of you who have not run into the reference to gut dysbiosis, it simply refers to the altered gut ecosystem that is reflected by unhealthy imbalances of the gut microbiota.And, as before, one significant driver of gut inflammation is the disordered ecological balance of the gut microbiota (dysbiosis).Additionally, bacterial overgrowth patterns of dysbiotic bacteria are highly associated with elevations of a potent gut-brain toxin— lipopolysaccharides.Lipopolysaccharides are bacterial surface molecules that are a major component of the outer membrane of Gram-negative bacteria.Lipopolysaccharides are normally shed by gut bacteria, but in the case of microbiome imbalances associated with bacterial overgrowth patterns (dysbiosis), a proliferation of dysbyotic bacteria—the bad guys, too much pro-inflammatory lipopolysaccharide matter is shed into the gut and peripheral circulation which can lead to powerful systemic toxic and inflammation reactions.With regard to the central n

Summary Hello and welcome to episode #16! Today I’ll be describing an elemental aspect in maintaining a healthy brain as you age and preventing the cognitive decline that is associated with unhealthy aging and the risk for Alzheimer’s disease as you age—brain detoxification. Because brain detoxification mechanisms are a very complex review, I will provide it in three parts–this episode and the next two. Now, most people that are oriented toward health and wellness strategies know that a good detox for their body is one of the more healthful things one can do for their wellbeing. But what about your brain? Well, there are also several key brain detoxification mechanisms that are often overlooked or not emphasized enough. And while detoxification programs and kits are extremely popular, the majority of detox programs I know of barely mention or address the challenge of brain detoxification. Now because brain detoxification mechanisms are a very detailed review, I will provide it in three parts–this episode and the next two. This episode will focus on the importance of a system of brain detoxification pathways and mechanisms that are vital to brain health and in risk reduction for late-onset Alzheimer's disease (LOAD)—the blood brain barrier (BBB) and the glymphatic system. The glymphatic system is now considered to contribute to approximately 60% of the brain’s beta-amyloid drainage to the cervical lymph nodes and further downstream. Both the glymphatic system and BBB are interconnected AND interdependent systems in the clearance of metabolic waste and neurotoxic proteins that are associated with Alzheimer's disease (AD)—beta-amyloid and tau protein—the two proteins that can accumulate and form the hallmark plaque and tangle lesions associated with AD in the brain. The glymphatic system was first described in a paper published 2012 by Dr. Maiken Nedergaard and his team at the University of Rochester Medical Center. Since then, many studies have investigated how it works and all the moving parts associated with the workings of the glymphatic system. So, let’s go over what the glymphatic system is...it is often described as a lymph like network as it was though that there were not any conventional lymphatic vessels in the brain as there is in the body. However, there is a lymphatic system that is integrated within the glymphatic system—the meningeal lymphatics which I describe in this episode. In short, the glymphatic system is composed of several essential parts that include the meningeal lymphatics to make it a functional apparatus that is essential in brain detoxification. To paint a picture in your mind of these related systems, the glymphatic system is where toxic protein and other waste material is collected and eventually drained into the blood stream, AND that waste is also exported into the meningeal lymphatic system and to the cervical lymphatic vessels and nodes which lie deep in the neck area. So, there are two exit routs for the glymphatic waste fluid—the blood and the meningeal lymphatics. Next week, I’ll describe what happens next to this metabolic waste once it is exported from the brain and into peripheral circulation. The Blood Brain Barrier and the Neurovascular Unit The glymphatic system is a glial or astrocyte-dependent waste clearance pathway in the brain, which also has a dynamic relationship with the both neurons and the cerebral vasculature. In fact, astrocytes fall into a family of brain cells termed the glia or neuroglia. Thus, the g in glymphatic or glia-lymphatic. Because there is a strong symbiosis between neurons and astrocytes, neuron

Summary Today, I'll review the formulations and research that illustrates the role of medical foods which are a unique classification of formulations that are approved by the FDA. Additionally, I will speak to the potential value of nutraceuticals and supplemental food-derived products in supporting cognitive health in aging individuals at risk for late-onset Alzheimer's disease (LOAD). And what are medical foods? Medical foods are defined products and nutrient formulations that are specifically designed for the dietary management of a disease. Medical food products are regulated by the FDA. Plus, medical foods contain nutrients or food-based therapeutic ingredients that provide a medical or health benefit, and thus the use of "medical" in the term. Three medical foods will be highlighted in today's episode that address three essential aspect of maintaining and optimizing cognitive function as you age—brain rejuvenation, brain protection (neuroprotection) and brain energetics (energy metabolism). With regard to brain rejuvenation, the formulation—Souvenaid® (Fortasyn Connect), which is available in Australia where it is designated as a "Food for Special Medical Purpose", and it is also available in Singapore and parts of Europe. Souvenaid® is a medical nutrition drink that contains a unique blend of ingredients known as Fortasyn® Connect, which is “formulated to support the growth of brain connections”, which means that it supports the synthesis of neuronal and synaptic membranes that are vital in synaptic function. And that is an important point that I cover in The Diabetic Brain in Alzheimer’s Disease. The Souvenaid formulation includes omega 3 fatty acids (EPA, DHA), phospholipids, choline, selenium, vitamin E, vitamin C, B12 B6, folic acid and uridine. Several studies and trials have evaluated the benefits of Souvenaid® and in a consensus opinion of those studies published in 2019 it was determined that there was improvement in memory and cognitive performance in patients with MCI and early Alzheimer’s disease. Nevertheless, it was also stated that “currently, there is not enough evidence to conclude that Souvenaid® decreases the rate of progression from MCI to dementia.” However, you will often see if you do a search for that product that it is described by a few sources, including the Souvenaid website, that the formulation is suitable “for the early stages of Alzheimer’s disease” which is often associated with MCI. And here is why: Several analyses and clinical trials have shown benefits in memory and cognitive performance in patients with MCI and early Alzheimer’s disease as the 2019 consensus opinion analyses reported. In the longest randomized clinical trial—3 years— in prodromal Alzheimer’s or MCI due to Alzheimer’s pathology—the LiPiDiDiet study, patients who were taking Souvenaid once daily for 3 years showed the following outcomes: Slowed the progression of memory and cognitive decline by 60%Reduced brain shrinkage by 33%Reduced the loss of everyday task performance by 45% The LiPiDiDiet study conclusions were: “This multi-nutrient intervention slowed decline on clinical and other measures related to cognition, function, brain atrophy, and disease progression. These results indicate that intervention benefits increased with long‐term use.” Those findings were published in January of 2021. The ingredient profile Souvenaid® formulation is designed for the rejuvenation of the critical membranes that surround the neuron which are particularly beneficial in the function of the synapse. Neuronal cellular membrane integrity is vital for th

SummaryIn today’s episode (#14), I’ll be providing an in depth overview one of the most powerful factors that underlies healthy body and brain aging—DIET!Indeed, healthy foods provide key nutrients and phytochemicals work to optimize cognitive function, and protect against dementia and Alzheimer’s in aging.However, since dietary therapies and specific foods in those diets that are linked to healthy aging is such a huge field of research, I’ll be focusing on a particular diet that has become a meaningful food template for the preservation and enhancement of brain health—The MIND Diet.Similarly, other studies have examined the benefits of other diets such as Japanese diet and the DASH diet in the reduction of risk for dementia and Alzheimer’s.In today’s review of these diets, I’ll also be referencing my version of The MIND Diet—The Improved MIND Diet, and of course, what distinguishes The Improved MIND Diet from all the other brain health and brain-saving diets.Now, what is so compelling about the research that underlies why these diets are so effective in many promoting a health body and brain in aging?After all, generations of moms and dads since Hippocrates espoused that “Food is Medicine”, have doggedly sought ways to get children into the habit of eating your vegetables for a healthy body and brain.Yes, we hopefully have all been coached to stick as many vegetables and fruits into out diets to optimize health and prevent common age-related diseases such as such as cardiovascular disease (CVD) and type 2 diabetes (T2D).However, the general public has little awareness of the marvelous body of evidence that points to a host of phytochemicals in fruits, vegetables and other foods that function as powerful activators of longevity wellness and a well-nourished brain that it takes for us to enjoy that ride.The research on the phytochemicals and particularly polyphenols and carotenoids abundant in those foods has become one of the most intense areas of study with regard to epigenetics, longevity medicine and in the prevention of many age-related diseases.Now a brief description of the MIND DietIn 2015 I ran across a report on the MIND Diet that incorporated two well recognized dietary models in their studies—the Mediterranean diet (MeDi) and the DASH diet, and the remarkable outcome in lowering the risk for Alzheimer’s disease.Dr. Martha Clare Morris-a nutritional epidemiologist at the Rush University Medical Center, and colleagues, were the authors of two studies that examined The MIND Diet food template compared to the foods specific to the MeDi and the DASH diet.The MIND Diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) concept was derived from the research that had demonstrated a protective benefit from both the Mediterranean diet and the DASH diet against dementia and Alzheimer’s disease.Thus, two MIND diet studies were initiated to determine if a hybrid MIND dietary pattern could be proven to ward of cognitive decline and Alzheimer’s disease.What separated the MIND Diet from their Mediterranean and DASH diet models was a modification of the MIND Diet foods that were used in the studies.The MIND diet modifications included an emphasis on leafy greens and berries to “highlight the foods and nutrients shown through the scientific literature to be associated with dementia prevention.”Why leafy greens?The choice of leafy greens was based on previous studies that revealed a lower rate of cognitive decline in study participants that consumed greater amounts of leafy greens over a variety of vegetables.In addition, the study authors remarked that: “Green leafy vegetables are sources of folate, vitamin E, carotenoids and flavonoids—a sub-class of polyphenols—critical nutrients that have been related to lower risk of dementia and cognitive decline.”M

SummaryToday I am very much looking forward to pod-talking about one of the most important components associated with accelerated aging processes, and in the risk for Alzheimer’s disease— the decline and inhibition of critical energy metabolism systems of the body and brain. Many studies have shown that alterations in mitochondrial energy metabolism, or bioenergetics, have been linked to numerous disorders that disrupt normal metabolism, and it is a factor in brain aging and a number of neurodegenerative diseases such as Alzheimer’s. Aging is associated with progressive mitochondrial dysfunction and deficits of ATP, which underlies “The Mitochondrial Basis of Aging” hypothesis. Now the role of mitochondrial function in biological aging and brain health is indeed vast, so I’ll keep the focus in this podcast on two key components of brain energy metabolism, or neuroenergetics—dysfunctional glucose metabolism and insulin resistance, and a few key risk factors that can increase the risk for both. Now, in brain energy metabolism, glucose is the most readily available fuel for youthful energy metabolism is glucose. However, in the aging brain there is often a progressive decline in glucose utilization and brain energy metabolism, or glucose hypometabolism, which is a known risk factor for cognitive decline and impairment. “The decline in brain energy metabolism distinguished by glucose hypometabolism and mitochondrial dysfunction are a significant set of related risk factors that are now viewed as early metabolic antecedents that set the stage for the development of late-onset Alzheimer’s disease (LOAD).” And, “Without the capacity to burn fuel for energy metabolism, an energy crisis is set forth in the neuron that gradually erodes our cognitive performance and sets the stage for the onset of late-onset Alzheimer's disease (LOAD).”Many studies have demonstrated that impairments in cerebral glucose metabolism and glucose hypometabolism to be a specific correlate to the cognitive dysfunction in the early stages of mild cognitive impairment (MCI), and to the eventual development of LOAD. Plus, studies have surmised that evaluations that show a reduction in cerebral glucose utilization can accurately predict future cognitive decline in normal individuals as well as the conversion to mild cognitive impairment. Now, a set of risk factors associated with aging are particularly notable in the risk for impaired glucose metabolism in the brain and the risk for cognitive impairment and dementia. Atherosclerosis,Brain insulin resistance,The ApoE4 genetic variant, andEstrogen deficits in women Lastly, I want to emphasize the role oxidative stress (OS)  with regard to mitochondrial function. In the body and brain, OS is the result of environmental exposures and endogenous production of free radicals from mitochondrial energy metabolism. Oxygen is required for mitochondrial ATP production and it is a major source of reactive chemicals that are potentially very damaging molecules. And, an environment of OS is created when there is not an adequate reserve or supply of antioxidants such as glutathione that neutralize damaging oxygen based free radicals that are termed—reactive oxygen species (ROS). An excess of  ROS and the induction of oxidative stress damages cells and their DNA and can lead to cell death. Case in point, in brain glucose hypometabolism and the mitochondrial dysfunction associated with it, excessive oxygen radicals are generated which overwhelm the normal antioxidant resources of the mitochondria and brain cells. Not to be overlooked in all of this is the fact that there are a host of laboratory-based bio

SummaryThis episode (#12) continues the overview of neurosteroids and their critical function in the protection and enhancement of cognitive function.In episode #11, I reviewed the role of “Testosterone, Progesterone and Allopregnanolone—Critical and Timely Neurosteroid Interventions in the Risk Reduction of Alzheimer's Disease.”, and this podcast will add DHEA and pregnenolone to that overview.The focus today will center around the pressing fact that the declines of steroid hormones such as DHEA and pregnenolone have pronounced effects on brain and longevity wellness.DHEA, pregnenolone, estrogen and progesterone and other hormones in anti-aging therapies has long been sought after by people striving for an increased quality of life and the enhancement of a more youthful vitality.Additionally, age-related decline of DHEA, and abnormal cortisol levels, have long been associated with and increased risk for numerous health disorders including insulin resistance and type 2 diabetes, obesity, osteoporosis, cardiovascular disease, hypertension, depression, and cognitive decline and dementia.Plus, in the brain chronic stress and excess cortisol patterns is linked to the demise of newly formed brain cells and the inhibition of a critical phenomenon associated with it—neurogenesis, in a key learning and memory center—the hippocampus.The inhibition of neurogenesis (the generation of new brain cells) by excess cortisol is a significant risk associated with brain and hippocampal shrinkage, and the depression and dementia associated with prolonged stress patterns.On the other hand, low cortisol in aging individuals is linked to memory problems and depression as normal cortisol function in the brain is in fact required for cortisol activation of glucocorticoid receptors and memory acquisition and consolidation.Optimizing pathways that promote neurogenesis and neuroplasticity as we age is vital to longevity wellness and healthy cognitive function.The generation and development of new nerve cells such as neurons in the brain, or neurogenesis, occurs throughout one’s lifetime and is perhaps the most critical phenomenon associated with modifying the risk for cognitive decline and dementia in aging.Many studies have shown that higher levels of neurosteroids such as DHEA, and allopregnanolone that is metabolized from progesterone and pregenenolone, induce neurogenesis and are protective against memory decline associated with normal aging and Alzheimer's disease.In this episode I also describe the role of DHEA and pregnenolone in modulating key synaptic receptors—NMDA, AMPA and GABA, which is a key dynamic in modulating calcium-related excitotoxicity.Excitotoxicity is a hallmark pathological insult linked to the progression of Alzheimer’s disease.DHEA, pregnenolone and their sulfated forms—DHEAS and Pregnenolone sulfate (PREGS), are protective factors against excitotoxic events.Both DHEA and pregnenolone and their derivatives also provide anti-inflammatory and antioxidant protection and counter beta-amyloid induced neurotoxicity.There is more so please listen in to get the rest of this essential overview on neuroteroids in longevity wellness and the protection against cognitive decline and the risk for dementia.God bless!Ralph Sanchez, MTCM, CNS, D.Homhttps://www.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolution/https://www.linkedin.com/in/ralph-sanchez/https://www.instagram.com/alzheimers_solution/https://twitter.com/RalphSanchez

In women, how important of a role does progesterone play in cognitive function?While a number of studies have shown that estrogen replacement therapy in women is protective against the risk for late-onset Alzheimer's disease (LOAD), only a few studies have demonstrated that progesterone also benefits cognitive function.Indeed, progesterone could be important in preserving cognitive function in women as they age—particularly in the menopausal transition when there is a precipitous drop in progesterone.Studies that investigated the protective role of hormone replacement therapy (HRT) in the potential prevention of LOAD have theorized that there is a "critical window" of opportunity for HRT in women.Research has demonstrated that early in menopause estrogen replacement therapy (ERT) may have a brain protective benefit, whereas ERT after 60 may increase the risk for LOAD.The same may hold true for progesterone replacement therapy.In 2021, a "University of Arizona Health Sciences study found women on hormone therapy were up to 58% less likely to develop neurodegenerative diseases including Alzheimer’s disease, and reduction of risk varied by type and route of hormone therapy and duration of use."The study included estrogens and progestins and combination therapies on neurodegenerative diseases. Note that progestins are synthetically derived forms of progesterone.In fact, the study "found that using the natural steroids estradiol or progesterone resulted in greater risk reduction than the use of synthetic hormones."Not often included in the studies centered around the potential role of HRT in the risk reduction of LOAD, is the role of estrogen and progesterone metabolites.A key progesterone metabolite—allopregnanolone, is linked to the generation of new brain cells—neurogenesis.In a study published in 2020, allopregnanolone was determined to be  "a first in class regenerative therapeutic for early AD that targets endogenous neural stem cells and disease-modifying mechanisms."In adult neurogenesis, neural stem cells and progenitor cells are the neural precursor cells that give rise to new brain cells, including astrocytes, microglia, oligodendrocytes and neurons.The phenomenon of adult neurogenesis is a critical component to a healthy aging brain and the potential prevention of cognitive decline and impairment that marks the development of LOAD.Please listen in to today’s episode and the continuing story on the role of hormones that are potentially a vital therapeutic intervention in both women and men at midlife.

In the U.S., two-thirds of diagnosed cases of dementia and Alzheimer's disease are women.A number of studies have shown that lower estrogen levels "before, during, and after menopause" is a risk for late-onset Alzheimer's disease.However, the risk factors associated with declining estrogen levels and late-onset Alzheimer's disease in women as they age is not widely known.Estrogen is a regulator of glucose metabolism in women and brain estrogen deficiency sets in motion a brain energy metabolism crisis in women—particularly after menopause.A decline in estrogen in menopause is commensurate with a decline in cerebral glucose metabolism.Thus, the inability to efficiently metabolize glucose in the aging brain (glucose hypometabolism) predicates the need for an alternate fuel to sustain the brain's high demands for energy .The demand for an alternate mitochondrial fuel in low estrogen states results in a compensatory shift to ketone metabolism that is enabled by the metabolism of fats derived from myelin-a nerve sheath substance that wraps around the axon extension of nerves.That catabolism of myelin (grey matter demyelination) is a signature hallmark of grey matter atrophy and the loss of brain volume, which in turn is a pathological feature in the progression of Alzheimer's disease in the aging brain.Plus, female ApoE4 carriers may be at higher risk for glucose hypometabolism and an earlier onset of myelin breakdown.Additionally, ApoE4-related mitochondrial dysfunction is also linked to the development of late-onset Alzheimer's disease.Since "mitochondrial DNA is maternally inherited and mitochondrial defects that contribute to the risk for brain metabolic deficits that include glucose hypometabolism and oxidative stress is seen in adult offspring of mothers with a history of Alzheimer’s.", optimizing mitochondrial function in the aging brain is of critical importance—particularly in ApoE4 carriers.Please listen in to episode # 10 for more on this vital association between estrogen deficiency and the increased risk for of late-onset Alzheimer's disease in women. Ralph Sanchez, MTCM, CNS, D.Homhttps://www.TheAlzheimersSolution.com https://www.facebook.com/TheAlzheimersSolution https://www.linkedin.com/in/ralph-sanchez https://www.instagram.com/alzheimers_solution https://twitter.com/RalphSanchez

The Gut-Brain Axis—what does that connection represent? Well, the gut-brain connection is often described as a bidirectional highway that is linked to many cause and effect health consequences, and many studies have explored the impact of the gut environment and microbiome on brain health in that gut-brain dynamic. Indeed, the role of the gut-brain axis is a significant factor in the risk for numerous health disorders throughout life, and it can have substantial implications on your body-brain health as you age. For example, numerous studies have examined the role of gut health and disorders such as small intestine bacterial overgrowth (SIBO) and inflammatory bowel disease (IBD), and their consequences on brain health that includes mood and mental health disorders. Additionally, significant research that links SIBO and pro-inflammatory disorders such IBD in the risk for cognitive decline and dementia has been accruing now for well over two decades and I have been following that science since the 1990s and to this very day. In today’s podcast, I’ll be sharing about the findings of a few studies that investigated aspects of the gut-brain axis with regard to the risk for cognitive decline and dementia in aging. On such study, a substudy of CARDIA titled Association of the Gut Microbiota With Cognitive Function in Midlife, it was determined that " gut microbial community composition, was significantly associated with cognitive scores in an analysis of middle-age CARDIA participants," The parent CARDIA study (Coronary Artery Risk Development in Young Adults), was initiated in 1985-86 for the purpose of “examining the development and determinants of clinical and subclinical cardiovascular disease and their risk factors.”, from young adulthood into middle age. Since its inception, the CARDIA study has investigated the role of several risk factors that affect cognition and brain health in aging including cardiometabolic disease (diabetes, heart disease, obesity) which is highly associated with an increased risk for dementia and Alzheimer's disease in aging. There are two main findings that I focus on in this podcast with regard to the CARDIA substudy (Association of the Gut Microbiota With Cognitive Function in Midlife) that were significant modifiers of the gut-brain axis and cognitive performance... a gut bacteria associated with SIBO and cognitive performance and, short chain fatty acids (SCFAs) which are beneficial metabolites produced by healthy fermentation of resistant starches—a fiber that functions as a prebiotic.I also briefly review the findings of a few studies on the neuroprotective benefit of several probiotic strains and probiotic therapy in modifying the risk for type 2 diabetes and late-onset Alzheimer’s disease. Please listen in to hear the rest of the gut-brain axis story!Ralph Sanchez, MTCM, CNS, D.Homwww.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchezhttps://www.instagram.com/alzheimers_solution

Today in episode # 8 I'll be reviewing the role of hypertension, obesity, type 2 diabetes and heart disease (cardiometabolic disease), and insulin resistance in your risk for late onset Alzheimer's disease.The metabolic and biochemical pathways by which cardiometabolic disease increases the risk for dementia and Alzheimer's later life is the central theme in my book: The Diabetic Brain in Alzheimer's Disease.The book thoroughly describes how and why the most prevalent age-related disorders of our time, put your brain and you at great risk for either vascular dementia, type 3 diabetes and Alzheimer's disease in later life. The podcast provides an audio summary on how obesity and cardiometabolic disease drive pro-inflammatory pathways and insulin resistance in the body and brain. and subsequently increase the risk for late-onset Alzheimer's disease.Plus, I'll also provide an overview about a couple of very important biomarkers risk factors—hemoglobin A1c and advanced glycation end-products (AGEs)— that are prime risk factors for not only diabetes and heart disease, but also for cognitive decline, dementia and Alzheimer's disease. Hemoglobin A1c and fasting glucose are biomarkers that are easily and widely available on blood tests and these biomarkers and many others should be carefully tracked as one ages—particularly if there is a family history of cardiometabolic disease, dementia or late-onset Alzheimer's disease.Please listen in!Ralph Sanchez, MTCM, CNS, D.Homwww.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchezhttps://www.instagram.com/alzheimers_solution

How does you unique genome increase the risk for Alzheimer's disease as you age?In todays episode—#7, I’ll be giving a comprehensive overview on the APOE gene, the ApoE4 genetic variant, and other genes and their genetic variants linked to the risk for late-onset Alzheimer's Disease (LOAD), and how, when, and why Alzheimer's takes root in certain individuals that are carriers of these genes and the variants associated with them.While the ApoE4 genetic risk variant is widely recognized as a risk factor for LOAD, how ApoE4 contributes to the risk for Alzheimer’s is not as so well recognized by most individuals.Indeed, the ApoE4 genetic variant is often highlighted as the most significant risk factor for LOAD, but how often have you run across the reasons why ApoE4 raises your risk for LOAD, and how other genetic variants may similarly and synergistically increase the risk for LOAD? Yes, many other risk variants add to the polygenic (more than one gene) disease profile of LOAD.The known functional and structural vulnerabilities linked to the ApoE4 variant are multifaceted, and I describe these functional and structural abnormalities that are linked to ApoE4 in my book, "The Diabetic Brain in Alzheimer’s Disease".However, since the mechanisms that underly the link between ApoE4 in LOAD are a vast topic, I focus on two key points—cholesterol and fat binding and transport, and beta-amyloid deposition and clearance from the brain.ApoE4, APOJ, ABCA1 and ABCA7, and TREM2 variants greatly determine how these two key mechanisms—cholesterol and beta-amyloid metabolism are factored into the risk for LOAD.Additionally, I briefly describe another very common variant—MTHFR 677T, that is a critical risk variant in methylation and homocysteine metabolism—yet another pathway that links the importance of the heart-brain axis in the risk for Alzheimer's disease.Please listen in and get ready for about 35 minutes of a revealing overview on the genes and their variants that are widely available in genetic profiling tests, and are major risk factors in LOAD.Ralph Sanchez, MTCM, CNS, D.Homwww.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchezhttps://www.instagram.com/alzheimers_solution

How early in your lifespan you can start to assess and track for specific biomarkers that are linked to the risk and earliest stages of late-onset Alzheimer's disease (LOAD), and have you given that much thought?In fact, there has been a significant shift in the progressive medical and research community over the last ten years in the understanding that you really have to start looking at your risk factors for LOAD earlier in life—at least by midlife, By midlife the brain damage associated with LOAD begins to hit a pivotal crisis point in terms of your risk for LOAD later in life—particularly if you are more susceptible to the disease.Now, I've talked about this in my book, and my articles and my social media posts many times as Alzheimer's disease has a long stage of development, and the prevailing wisdom over these last few years has been that it has a timeline of 20 to 30 years or so where it develops.And bear in mind, it is a silent disorder in the asymptomatic stage of LOAD—the preclinical stage, which might have its roots in cardiometabolic disease (type 2 diabetes/cardiovascular disease).Case in point, the findings of a recently published study—an offspring study of the Framingham Heart Study, revealed that: “These findings show for the first time that cardiovascular risk factors, including HDL which has not been consistently reported as a strong risk factor in Alzheimer's disease, contribute to the risk of Alzheimer's disease starting as early as age 35.” (Dr. Zhang)Undoubtedly, if you have a family history of cardiometabolic disease, or dementia, it is critical to start looking at these risk factors earlier in life.The pathology linked to the late-onset Alzheimer's disease continuum and vascular dementia spans decades, and it can be arrested or reversed in the early stages of the disease process.Think ahead!Please listen to the podcast to get the rest of the story!Ralph Sanchez, MTCM, CNS, D.Hom.BrainDefend®www.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchezhttps://www.instagram.com/alzheimers_solution

In the fifth episode of The Alzheimer’s Solutions Revolution podcast with Ralph Sanchez, I talk with my co-host Susan Brender, as we continue with our special podcast series called Think Ahead. In this week’s episode, I'll provide an overview on the role of tau protein and neurofibrillary tangles (tau tangles) in the progression and development of late-onset Alzheimer's disease (LOAD).The toxic accumulation of tau tangles in brain cells (neurons) are one of the two hallmark lesions associated with Alzheimer's disease (AD). The aggregation of beta-amyloid peptides (protein) into amyloid plaque is the other toxic hallmark lesion linked to the onset and progression of LOAD. Additionally, I'll give an a summary on the importance that tau protein plays in a critical component in the conveyance network and cytoskeletal structure that is an essential element of neuronal function and structure.The cytoskeletal conveyance structure of the neuron contributes to the shuttling of mitochondria to the neurons axonal terminal and synapse in order to provide the energy metabolism required for synaptic function. Please listen in and be informed!Ralph Sanchez, MTCM, CNS, D.Homwww.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchezhttps://www.instagram.com/alzheimers_solution

In this Alzheimer's Solution Revolution episode #4, I’ll give an overview of episode #3, and I’ll provide several key insights about a protein that is associated with the pathology of Alzheimer’s disease—beta-amyloid protein, which forms the proverbial amyloid plaque that is often cited as a principal lesion of the disease process.Additionally, in this Think Ahead podcast, I pick up where we left off on the last episode (#3) with regard to the genesis of Alzheimer’s, disease in the brain, and the role of beta-amyloid protein aggregates in the progression of Alzheimer’s disease in aging. I illustrate how the disease process can progress from the preclinical stage (asymptomatic) to a mild cognitive impairment stage, and eventually a diagnosis of a dementia associated with Alzheimer's disease,Please listen in to continue learning how amyloid precursor protein is processed to produce beta-amyloid protein particles and aggregates, which underlies the earliest stage (preclinical) of the Alzheimer’s disease continuum that can span decades before an eventual diagnosis of dementia.Lastly, we touch on the role of the APOE gene and the ApoE4 variant—the most validated late-onset Alzheimer’s disease genetic risk variant— with regard to beta-amyloid accumulation in the brain, and how research has significantly progressed over the years to illuminate how we can leverage these new findings to reduce the risk for late-onset Alzheimer’s disease.We end with what to anticipate in an additional podcast coming soon in the Think Ahead series—the role of tau protein and neurofibrillary tangles in Alzheimer’s disease.Ralph Sanchez, MTCM, CNS, D.Homwww.TheAlzheimersSolution.comhttps://www.facebook.com/TheAlzheimersSolutionhttps://www.linkedin.com/in/ralph-sanchezhttps://www.instagram.com/alzheimers_solution