The Importance of Routine Psychometric Testing for Mild Cognitive Impairment in Geriatric Populations

Author: VP Grewal, MD. 2020 September 3.

The National Institute on Aging and Alzheimer’s Association (NIA-AA) defines Alzheimer’s Disease (AD) as a progressive disease with three stages, an asymptomatic pre-clinical stage, mild cognitive impairment (MCI), and Alzheimer’s dementia. In AD, there is an accumulation of β-amyloid protein at neuronal synapses, eventually leading to synaptic failure and neuronal death. Intracellularly, tau proteins accumulate which inhibit the transport of nutrients and other essential molecules, hastening the process the cell death. Initially the patient is able to compensate for the neuronal changes and shows no cognitive decline. Eventually, basic bodily functions such as swallowing are impaired. Patients will ultimately become bed-ridden, and will typically die from external factors such as pneumonia and infected pressure ulcers. The time of disease progression is highly variable among individuals.

MCI is an intermediate stage between the cognitive decline of normal aging and dementia. MCI will often, but not always, progress to dementia. Causes of MCI include neurodegenerative disease, medications, depression, vascular problems, and other disease processes. The cognitive deficit of MCI may not interfere with a patient’s ability to function independently. Patients will often attribute the subtle symptoms to aging or stress. The revised Mayo Clinic Criteria classifies MCI into two categories, amnestic MCI (a-MCI) and non-amnestic MCI (na-MCI). a-MCI primarily effects episodic memory, and na-MCI primarily effects language, decision-making, judgement, time-perception, or visuospatial abilities. Studies show up to 70% of those with a-MCI will develop Alzheimer’s, while other variants will develop dementia of other causes. The conversion rate from MCI to AD is estimated to be 15% per year. Those who revert back to a normal cognitive state, have an increased risk for entering MCI again, and for developing dementia. In a 2015 study of 1449 cognitively normal subjects, aged 70 to 89, in Olmsted County, Minnesota, 401 or 27.7% developed MCI. Although there are no medications currently approved for MCI, there is some evidence that cognitive training, aerobic exercise, dietary modifications, and nutritional supplementation may improve cognitive functioning.

In the research field, early MCI detection is crucial to study interventions that delay progression. In a clinical setting, early MCI detection is important because it allows physicians to rule out any non-AD causes, consider non-pharmacological intervention, and explore participation in clinical research trials with the patient. Patients and their families also benefit from identification of MCI as they can make future preparations while the patient is in a capable cognitive state.

Assessing the progression from MCI to Alzheimer’s dementia requires routine psychometric assessments. The use of formal psychometric testing by primary care practitioners for diagnosing dementia was estimated to be only 58%, with the main reported barrier being lack of time. Furthermore, commonly employed psychometric tools such as the Alzheimer’s Disease Assessment Scale (ADAS-cog) and Mini-Mental Status Exam (MMSE) are useful in monitoring AD progression, but lack sensitivity for MCI. The Clinical Dementia Rating Scale (CDR) was one of the first assessment tools that showed sensitivity for MCI, assessing daily functional activity, interviewing both patient and a caregiver. Unfortunately, the CDR is primarily subjective and has a long administration time.

The Montreal Cognitive Assessment (MoCA) is a psychometric tool developed by Dr. Z Nasreddine. The scale specifies parameters for normal controls, MCI, and AD, and estimates up to 90% specificity for MCI. Recent date indicates a statistically significant correlation with existing scales in terms of total score and individual parameters. The administration time for the MoCA is less that 10 minutes. It currently does not require any specific training or certification for administration, but does require an expert in the cognitive field to interpret the results. The ease of administration, accuracy, and sensitivity for both MCI and AD allows the MoCA to serve as a routine cognitive assessment by health care providers.

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Type-3 Diabetes as Alzheimer’s Disease: Hyperinsulinemia as a mechanism in Alzheimer’s Pathology

Author: VP Grewal, MD. 2020 Feb 19

The world is currently facing a diabetes epidemic, affecting over 400 million people worldwide. This figure is more likely to be double, as one in two people currently living with diabetes are undiagnosed. Type 2 diabetes is the most commonly known form of diabetes and without prompt diagnosis and management can lead to complications such as blindness, limb amputation, kidney disease, heart attack and stroke. In congruence with the rise of diabetes mellitus (DM) in the past century, humanity is facing another epidemic, dementia, which currently afflicts more than 35 million people worldwide. Almost half of people with dementia have Alzheimer’s disease (AD), the most common form, characterized by progressive memory, cognitive and behavioral deficits.

In a 2016 study published in the journal Diabetologia (the journal of the European Association for the Study of Diabetes), researchers uncovered that genes responsible for the production of toxic neuroproteins not only lead to Alzheimer’s symptoms, but also lead to diabetic complications. In response to the study results, lead researcher, Professor Bettina Platt stated, “Many people are unaware of the relationship between diabetes and Alzheimer’s disease, but the fact is that around 80% of people with Alzheimer’s disease also have some form of diabetes or disturbed glucose metabolism. This is hugely relevant as Alzheimer’s is in the vast majority of cases not inherited, and lifestyle factors and comorbidities must therefore be to blame.” The connection between Alzheimer’s disease and diabetes is so close, that researchers have now begun referring to Alzheimer’s as “type 3 diabetes”.

Scientists hypothesize that the pathological process leading to the development of AD encompasses two main features: amyloid plaques and neurofibrillary tangles. Amyloid plaques form as a result of the extracellular accumulation of beta-amyloid (Aβ), believed to trigger a cascade of events leading to neurodegeneration, and is the primary therapeutic target in AD pharmacotherapy. Neurofibrillary tangles (NFTs) on the other hand are intracellular inclusions, formed by the aggregation of tau proteins, which are microtubule-associated proteins that function to stabilize microtubules. Cognitive decline in AD is closely correlated with the progressive pathological accumulation of NFTs, believed to directly cause neuronal malfunction and cell death. Extensive clinical research has focused on Aβ or tau proteins as therapeutic targets, but clinical trials have had disappointing results thus far. The most promising therapeutic strategy, on the other hand, may be focusing on risk factors such as DM.

Science has only recently accepted the role of insulin in the brain, which include neuronal development, synapse formation, learning and memory, glucoregulatory function and feeding behavior. Researchers suspect that the high concentration of insulin found in the brain is the result of local production in the brain and active transported across the blood-brain-barrier via a specific transporter, affected by hyperglycemic states such as diabetes.

Several independent research groups have shown insulin resistance to have a significant effect on Aβ synthesis, aggregation, and clearance mechanisms. The studies demonstrated that diet-induced insulin resistance increases Aβ synthesis on a molecular level, and also correlated excessive sucrose intake with increased cerebral Aβ peptide levels and worsened learning impairment in Alzheimer’s transgenic mice. Furthermore, insulin-degrading enzyme (IDE) is an important enzyme involved in the proteolytic degradation of accumulated Aβ in the brain. In states of hyperinsulinemia, as in DM, excessive insulin levels directly compete with Aβ for IDE, reducing Aβ degradation and increasing Aβ levels.

Physiologically, tau proteins are involved in stabilizing neuronal microtubules. In pathological states, such as AD, tau proteins undergo phosphorylation leading to aggregation, the formation of neurofibrillary tangles and neuronal toxicity. Glycogen synthase kinase-3 (GSK-3) is an important regulator of tau phosphorylation. Studies have shown that diabetes and obesity-induced insulin resistance cause excessive activation of GSK-3β which induces tau hyper-phosphorylation, leading to the formation of neurofibrillary tangles responsible for the cognitive changes in AD. Activation of GSK-3 is another suspected mechanism in which diabetes triggers the development of or accelerates the progression of AD.

With aging demographics and current trends, the number of people affected by dementia is expected to reach 115 million by 2050. This trend is not only devastating for individuals burdened with the disease, but also families forced to care for their loved ones. Furthermore, the economic impact on society is immense, with the Alzheimer’s Organization predicting Alzheimer’s and other dementias could cost the United States of America almost $1.1 trillion by 2050.

A optimal method to reduce the personal, social, and economic impacts of the DM and AD epidemics is through prevention, which can be best achieved through dietary changes and physical exercise. One simple dietary change involves substituting sucrose or table sugar for low-glycemic alternatives such as vitaSWEET in cooking, baking, and beverages. vitaSWEET is all-natural and as sweet as sugar, but without the metabolic consequences.

References:

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The Role of Hyperglycemia-Induced Endothelial Dysfunction in Diabetes, Atherosclerosis and Inflammatory Disorders

Author: VP Grewal, MD. 2020 Apr 12

The prevalence of type 2 diabetes mellitus (T2DM) has tripled in the past three decades, with 2014 figures estimating 422 million diabetics worldwide. Additionally, half of those with diabetes are currently undiagnosed. Hyperglycemia is the primary feature of T2DM, and is most often caused by metabolic abnormalities. Pre-diabetes precedes the onset of T2DM by several years and encompasses early metabolic changes called impaired fasting glucose. Vascular complications in T2DM increase in proportion to the duration of hyperglycemia. Chronic hyperglycemia triggers endothelial dysfunction, the primary factor in the pathogenesis of diabetic vascular complications. Furthermore, emerging research has identified hyperglycemia induced endothelial disfunction to play a significant role in the pathogenesis of atherosclerosis and other inflammatory disorders.

Endothelial cells (ECs) line the internal surface of all blood vessels, and serve as a barrier between circulating blood and tissues. ECs are crucial in the regulation of vascular tone and maintenance of vascular homeostasis. Under normal physiological conditions, ECs exist in a dormant state, but under various mechanical and chemical stimuli, ECs synthesize and secrete many vasoactive substances and growth modulators. ECs are particularly sensitive to changes in blood glucose levels, and hyperglycemic conditions induce acute endothelial inflammation, and a prolonged pro-inflammatory state leading to endothelial dysfunction.

Endothelial dysfunction is characterized by a loss of balance between vasoconstrictors and vasodilators, growth promoting and inhibiting factors, pro-atherogenic and anti-atherogenic factors, and pro-coagulant and anti-coagulant factors. This disruption in vascular homeostasis is caused by reduced nitric oxide production, increased endothelial permeability, increased expression of adhesion molecules, and increased apoptosis. Endothelial dysfunction is responsible for the vascular complications associated with T2DM, and is believed to play a significant role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis, asthma, cerebral small vessel disease, and autoimmune disorders such as inflammatory bowel disease. Furthermore, emerging research has identified endothelial dysfunction as an early pivotal event preceding the development of coronary artery atherosclerosis.

Researchers hypothesize the risk of developing autoimmune diseases, diabetes, and atherosclerotic coronary artery disease to be directly related to the number, intensity and duration of hyperglycemic events. The modern diet is rampant with refined sugar products and beverages with high-fructose corn syrup which cause massive spikes in blood glucose levels. A simple dietary modification to reduce hyperglycemic episodes and associated endothelial dysfunction is to supplement sugar with low-glycemic alternatives such as vitaSWEET, an all-natural sugar alternative, that is as sweet as sugar, bakes like sugar, but without the metabolic consequences.

References:

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Dietary Sugar and the Childhood Obesity Epidemic

Preventing childhood obesity is vital due to its association with lifelong obesity, metabolic disorders such as type-2 diabetes mellitus and hypertriglyceridemia, obesity-related cancers, in addition to psychosocial repercussions and decreased educational attainment. From 1975 to 2016, mean BMI and obesity rates in children and adolescents aged 5-19 years have increased globally and in most regions.

Added sugar consumption is the primary factor associated with childhood obesity trends, in addition to being associated with other detrimental health conditions such as dental caries, asthma, altered lipid profiles, hypertension, and cancer. A 2019 analysis of data compiled from the Centers for Disease Control and Prevention (CDC) from 2011 to 2016 revealed 98% of American toddlers and 60% of infants consume added sugar in sweetened foods and beverages. Sweet bakery products were in the top 3 sources of added sugar for both toddlers and infants. Previous studies examining sugar intake in older children (aged 2-8 years) also reported sweet bakery products to be one of the top three sources for added sugar. Fruit drinks, yogurt, and sugar-sweetened beverages were other important sources of added sugar identified by researchers. In 2015, the World Health Organization (WHO) and the American Heart Association (AHA) recommended limiting added sugars consumption to <10% of total caloric intake for children aged 2 to 19 years. In 2017, the AHA released a statement advising children less than 2 years to old to avoid consuming added sugars entirely. The most recent analysis of CDC data revealed about 70% of American children older than 2 years exceed recommendations for added sugars intake.

Infants and children around the world exhibit a heightened preference for sweetness, most likely a biological underpinning to confer advantage in environments of scarcity. Moreover, emerging research has shown significant similarities in neurochemistry and behavior between consumption of added sugars and drug-like effects, including bingeing, craving, tolerance, withdrawal, cross-sensitization, cross-dependence, reward and opioid effects. Sugar addiction appears to develop as a result of natural endogenous opioids released upon sugar consumption. The opioid-like pain reducing properties of sugar are evident from birth. A sweet solution placed in a newborns mouth, elicits facial relaxation, often accompanied with a smile. Furthermore, something sweet placed on the tongue of a crying newborn produces an instantaneous calming effect. In another study, sucrose consumption delayed pain reporting in children aged 8 to 11 years old undergoing a cold-induced pain stimulus test, whilst having no effect in adult. Evolutionary driven taste preferences, coupled with heightened response to natural endogenous opioids produced upon sugar consumption make infants and children more vulnerable to sugar addiction than adults.

While it may not be reasonable to eliminate sweet foods entirely from a child’s diet, substitution of sugar with an all-natural sweetener such as vitaSWEETis a practical approach to abate the rising trends in childhood obesity and other detrimental health ailments associated with added sugar consumption. vitaSWEET is as sweet as sugar, zero calories, has no effect on blood glucose levels, and is safe for children.

References:

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Autism and Gestational Diabetes: The Importance of Managing Pre-Pregnancy Prediabetes

Author: VP Grewal, MD. 2020 May 17

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance a woman develops during gestation, typically recognized during the latter half of pregnancy. A review of the global prevalence of GDM on the basis of studies between 2005 and 2018, estimated the global prevalence of GDM to range from 1% to > 30% depending on region and country, as seen in Figure 1.0 below.  The majority of women are normoglycemic after delivery, but as many as 20% have impaired glucose tolerance in the early postpartum period. Furthermore, after the development of GDM, women have an up to 70% risk for recurrent GDM in future pregnancies, a seven-fold higher risk of overt diabetes in the proceeding 5-10 years, and an increased risk of cardiovascular diseases. The short-term perinatal consequences of GDM include pre-eclampsia, preterm delivery, primary caesarean delivery, shoulder dystocia or birth injury, high birthweight, high neonate body fat percentage, neonatal hypoglycemia, and newborn intensive care admission. Long-term outcomes of the offspring include obesity and glucose intolerance. Additionally, emerging research has linked prenatal diabetes as a significant risk factor for long-term neuropsychiatric morbidity, in particular Autism spectrum disorder (ASD) in children.

ASD is a neurodevelopmental disorder characterized by impairments in socialization, communication and language, and repetitive or unusual behaviors. ASD typically appears during the first 5 years of life and persists into adulthood. Individuals with ASD often have co-exiting neuropsychological conditions such as epilepsy, depression, anxiety, and attention deficit hyperactivity disorder (ADHD). The prevalence of ASD has increased dramatically since the 1960s and continues to rise annually at an exponential rate. ASD diagnoses in children have increased from 1 in 150 in the year 2000, to 1 in 59 in 2018, with autism prevalence increasing by 119.4% in this time period. On average, autism costs families $60,000 USD per year, and the cost of taking care of Americans with ASD is expected to reach $451 billion by the year 2025.

The prevalence rates of ASD and GDM have both increased dramatically since the 1960s, in congruence with the global epidemics of diabetes and obesity and societal trend for childbearing at a later age. In the United States, 29.3% of adults 20-22 years of age have detectable pre-diabetes, and it is highly possible that many of GDM cases are actually undiagnosed pre-pregnancy hyperglycemia of varying severity. In addition to pre-pregnancy prediabetes and obesity, other risk factors for GDM include childbearing after the age of 30, positive family history, cigarette smoking, psychological stress, exposure to organic pollutants and endocrine disrupters, and pre-pregnancy dietary factors. Data from observational studies suggests that as many as 45% of GDM cases may be preventable by adherence to a healthy lifestyle.

With the emerging evidence of GDM as an independent risk factor of ASD in children, there is an urgent need to address the epidemics of prediabetes, diabetes, and obesity in women of childbearing age. Emphasis on lifestyle modifications is currently the best approach to reduce GDM and hence the risk of ASD in children. Added sugar consumption is one of the most significant causes of glucose abnormalities and appears to increase the risk for GDM, as seen in a study by Chen et al. whom identified a 22% greater risk for GDM in women consuming five or more servings of sugar-sweetened cola per week. One simple method to reduce dietary sugar consumption is through the substitution of sugar for an all-natural alternative such as vitaSWEET, which is as sweet as sugar, zero calories, has no effect on blood glucose levels, and is safe during pregnancy.

References:

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Sugar and Aging: The Role of Advanced Glycation End-Products (AGEs) in Aging & Chronic Disease

Aging is the result of progressive physiologic changes which occur until senescence, due to a decline in biochemical functions and capacity to adapt to metabolic stress. The abnormal accumulation of biological waste plays a significant role in organ or tissues functional deterioration as we age.

Advanced Glycation End-Products (AGEs) are a complex group of compounds consisting of proteins, lipids, or DNA which undergo glycation when exposed to sugars. The human body lacks enzymes to eliminate glycated products, which progressively accumulate as metabolic waste during aging. The glycation reaction results in impaired protein function and reduced elasticity of tissues such as blood vessels, skin, and tendons.

Hyperglycemia vastly accelerates the glycation process, with AGE accumulation playing a significant role in the microvascular and macrovascular damage associated with diabetes mellitus.  In addition to diabetes, many other chronic diseases such as atherosclerosis, chronic kidney disease, rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, vascular dementia, cataracts, other degenerative ophthalmic diseases, and many other diseases are associated with the accumulation of AGEs in tissues. Furthermore, there is significant evidence that AGEs contribute to sarcopenia and the loss of bone density and muscle mass associated with aging.

Cooking or consuming sugars with fats or proteins results in the most significant generation of AGEs. A study using a mouse model, given an AGE-rich diet for 16 weeks resulted in a 53% increase in serum AGE levels. Currently there is considerable interest in discovering potential inhibitors of AGE formation or agents that may disintegrate and eliminate AGEs. Of the several AGE inhibitors and breakers discovered including aminoguanidine, N-phenacylthiazolium bromide, and alagabrium, none are in clinical use due to safety concerns. Recently, interest in herbal products has been rising, some of which have similar or even stronger anti-AGE than synthetic drugs, with a much more favorable safety profile. Flavanoids, a class of polyphenols, including kaempferol, genistein, guercitrin, quercetin, and epicatechin appear to have potent anti-glycation properties, and are currently the most promising pharmaceutical approach to manage AGE accumulation.

As with most of medicine, the best treatment is prevention, and thus diet and exercise are the easiest way to reduce AGE accumulation, slow the aging process, and avert the onset of chronic disease. The simplest change one can make is avoiding sugar in cooking, baking, sauces, and beverages, and supplement with low-glycemic alternatives such as vitaSWEET, an all-natural sugar alternative, that is as sweet as sugar, bakes like sugar, but without the metabolic consequences.

References:

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vitaSWEET – an ancient alternative as sweet as sugar, but without the metabolic consequences

Much of illness afflicting modern society can be attributed to changes in eating patterns.  In the past 160 years the amount of sugar consumed by society has exploded, attributed to the mechanization of sugar production.  This trend is not limited to the developed world, but has impacted almost every country on the planet.  Sugar is not only found in obvious foods such as deserts, it has also become a hidden ingredient in many foods available on the market today.  In recent years, financial incentives have driven companies such as Pepsi and Coca Cola to replace sugar with sugar with high-fructose corn syrup in certain products, such as soft drinks and processed foods.

Both sugar and high-fructose corn syrup are very high on the glycemic index, meaning that they cause blood glucose levels to rise rapidly.  This shocks the body, which responds by releasing massive amounts of insulin to drive the excess sugar into the cells of the body.  Over time, a constant elevation of blood glucose and insulin levels, leads to a the development of insulin resistance, a compensatory response in which the cells remove insulin receptors from their membrane. The subsequent effect is an even greater amount of insulin required to return blood glucose levels to normal amounts.  Eventually this leads to the development of diabetes mellitus.

In addition to diabetes, recent literature has correlated elevated blood glucose levels and insulin resistance with a wide array of health problems, including obesity, metabolic syndrome, hypertension, dyslpidemia, and hepatic steatosis. Furthermore, a high baseline insulin level is also highly inflammatory and can worsen autoimmune conditions such as arthritis, inflammatory bowel disease, multiple sclerosis, and vasculitis.

vitaSWEET is a natural alternative to table sugar and high fructose corn syrup, that is 0 on the glycemic index, meaning that it has no effect on blood glucose levels.

vitaSWEET is formulated with two simple ingredients: monk fruit and erythritol.  Monk fruit or luo han guo is native to southern China and northern Thailand, and has almost 300 times natural sweetness than that of sugar.  It has been used for centuries in traditional Chinese medicine, first mentioned in the records of 14th century Chinese monks.  Erythritol is a naturally occurring sugar alcohol derived from fruits and plants.  Vita Columbia’s unique blend of both monk fruit and erythritol is as sweet as sugar and can be used as a 1-to-1 replacement in recipes.