Tag Archives: vitamin b

Homocysteine and Dementia: Impact of Nutrition on Neurodegeneration

This week’s article is a guest post by Dr. Nafisa Jadavji, a research associate and lecturer at Carleton University and the University of Ottawa. To submit your own guest post to AlzScience, please contact us.

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High levels of homocysteine have been implicated in neurodegenerative diseases, such as dementia, mild cognitive impairment, and Alzheimer’s disease. Homocysteine can be measured in blood easily, which has led to several studies in humans reporting that elevated levels of homocysteine lead to increased risk of developing neurodegenerative diseases or affect progression. Interestingly, homocysteine levels in our bodies increase as we age.

Vascular cognitive impairment (VCI) is the second leading cause of dementia after Alzheimer’s disease.  VCI is the result of reduced blood flow to the brain, however, the pathology is not well understood. Reduced blood flow ben be a result of age and health (e.g. high cholesterol). The clinical presentation of VCI varies, most the patients have some degree of cognitive decline. There are currently no treatments for VCI since the actual pathology remains unknown.

Nutrition is a risk factor for VCI, specifically high levels of homocysteine. High levels of homocysteine can be reduced by B-vitamins, like folates or folic acid. Folates are the natural occurring form of the vitamin, these are often found in food such as green leafy vegetables or liver. Whereas folic acid is the chemically synthesized form that is often taken in supplemental form.

My research program focuses on how nutrition affects the brain, specifically how folates affect neurodegeneration.

Using a mouse model of VCI we have reported that deficiencies in folates, either dietary or genetic, affect the onset and progression of VCI. Using the Morris water maze task, we report that mice with VCI and folate deficiency performed significantly worse compared to controls. We assessed changes in the brain using MRI and interestingly found that folate deficiency changed the vasculature in the brain of mice with VCI. Because of either a genetic or dietary folate deficiency, all the mice had increased levels of homocysteine. However, we did not observe any significant association between elevated levels of homocysteine and behavioral impairment or changes in the brain tissue of VCI affected mice.

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In the Morris water maze, a mouse is placed in a pool and must swim to find a hidden platform. The mouse’s memory is measured based on how long it takes to find the platform after it’s placed in the pool a second time. Image source

Our results suggest that it is not elevated levels of homocysteine making the brain more vulnerable to damage, but the deficiency in folates, either dietary or genetic that changes the brain. In the cell, folates are involved in DNA synthesis and repair as well as methylation. These are vital functions for normal cell function. Therefore, reduced levels of folate may be changing the cells in the brain and making them more vulnerable to any types of damage. I would like to suggest that high levels of homocysteine may just be out put measurement of some sort of deficiency (e.g. reduced dietary intake of folates). Several studies using brain cells that are grown in petri dishes have reported that extremely high levels of homocysteine need to be added to cells to cause damage. These levels are usually not observed in humans.

In terms of future directions, more research is required to understand how deficiencies in folates, homocysteine and other nutrients that reduce levels of homocysteine like choline change cells in the brain throughout life and how these changes are related to neurodegeneration.

For more information about my research please visit my personal website.

 

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Is It Really Alzheimer’s? 10 common misdiagnoses you should know about

Doctors misdiagnose a patient with Alzheimer’s disease at alarmingly high rates, when the true cause may be a different (and often treatable) disease. In 2011, researchers conducted autopsies on the brains of 211 men who had been diagnosed with Alzheimer’s while they were alive. They found that nearly half of the brains did not possess the necessary pathology to meet an Alzheimer’s diagnosis [1]. A 2012 study reported similar misdiagnosis rates by physicians at the National Institute on Aging’s Alzheimer’s Disease Centers [2].

An incorrect Alzheimer’s diagnosis can cause a person to pay $9,500 to $14,000 annually in unnecessary medical procedures and medications [3]. Even worse, it may result in the true cause of the dementia symptoms going untreated, hastening the rate of cognitive decline. To give you the tools to reduce the risk of a misdiagnosis, I’ve compiled this list of ten common conditions that can mimic the symptoms of Alzheimer’s disease. If you or a loved one has been diagnosed with Alzheimer’s disease, be sure that you request tests to rule out these other possibilities.

1. Medication side effects

More than 100 medications can have side effects resembling symptoms of Alzheimer’s. These include a wide variety of common meds including Benadryl, Ambien, Valium, Xanax, and Lipitor [4]. It is particularly important to inform your doctor if you are on anticholinergic drugs, which include many antihistamines, antipsychotics, antidepressants, and muscle relaxants, among others [5]. These drugs block the function of a neurotransmitter called acetylcholine, which can lead to cognitive impairment [6].

2. Normal pressure hydrocephalus

The central nervous system is surrounded by cerebrospinal fluid, which cushions the brain and regulates cerebral blood flow. For unknown reasons, cerebrospinal fluid can sometimes build up in the brain cavities (ventricles) and cause them to swell, resulting in a condition called normal pressure hydrocephalus (NPH). The symptoms of NPH include progressive dementia, difficulty walking, and urinary incontinence [7]. According to the Hydrocephalus Association, NPH affects an estimated 700,000 Americans, though only 1 in 5 of these people receive the correct diagnosis [8]. As many as 10% of patients diagnosed with Alzheimer’s or other forms of dementia may actually have NPH [9]. This condition is easily detected using brain scans and can often be treated by surgically draining the excess fluid from the ventricles. Additional reading on NPH: [10], [11], [12]

3. Vascular dementia

Vascular dementia is the second most common form of dementia after Alzheimer’s. It is caused by a stroke, multiple “mini strokes,” or other cardiovascular disturbances, and can cause similar symptoms to Alzheimer’s [13]. A 2013 study found that 17% of vascular dementia patients were previously given an incorrect diagnosis for Alzheimer’s disease, which led to significantly increased medical costs [14]. Vascular dementia is very difficult to distinguish from Alzheimer’s, and the possibility of misdiagnosis should be considered if the patient has risk factors such as high blood pressure, diabetes, or smoking. There is currently no cure for vascular dementia, but steps may be taken to improve cardiovascular health and reduce the risk of further cognitive decline [15].

4. Vision or hearing loss

Cognitive evaluations such as the Mini-Mental State Examination (MMSE) may yield an incorrect diagnosis of Alzheimer’s disease if a patient is experiencing undiagnosed vision or hearing loss. Studies have shown that individuals with visual [16] or auditory [17] impairments score lower on the MMSE, despite being cognitively normal. Both of these conditions are common among the elerly population. Studies estimate that among individuals over the age of 70, 18% are visually impaired, 33% are hearing impaired, and 8% are both visually and hearing impaired [18]. Regular vision and hearing exams could not only prevent an incorrect diagnosis but also improve the overall quality of life for these patients [19], [20].

5. Depression

Depression can often mimic the early symptoms of Alzheimer’s disease. These include mood changes, withdrawal from daily activities, sleep disruptions, and difficulty concentrating [21]. Depression affects more than 1 in 20 elderly adults and the risk may be increased by the death of a spouse or chronic illness, as well as certain medical or psychological conditions [22]. The symptoms of depression can often be improved through a combination of medications and psychotherapy.

6. Thyroid problems

The thyroid gland produces hormones that regulate metabolism and other body functions. The American Thyroid Association reports that 12% of Americans will develop thyroid problems in their lifetime, and more than half of them are unaware of their condition. Both hypothyroidism and hyperthyroidism can have symptoms resembling Alzheimer’s, including forgetfulness, mood changes, and sleep disturbances. Thyroid problems are often treatable but can cause serious complications if left undiagnosed [23].

7. Vitamin B12 deficiency

Vitamin B12 plays multiple important roles in the nervous and circulatory systems. It is most commonly found in meat, fish, and dairy products. As many as 9% of Americans are deficient in this essential nutrient [24]. Risk factors include a vegetarian or vegan diet without B12 supplements, heavy alcohol consumption, and long-term use of acid-reflux medications. Vitamin B12 deficiency can lead to dementia and changes in mood or personality, which may be mistaken for Alzheimer’s [25]. Individuals with an Alzheimer’s diagnosis might consider requesting a blood test for B12 levels, or increasing their intake of B12 in the form of supplements, fortified cereals, and B12-rich foods to see if their cognitive symptoms improve.

8. Urinary tract infection

Urinary tract infections (UTI’s) are the most common bacterial infection in the United States. They primarily affect women; nearly half of all women will experience at least one UTI in their lifetime [26]. When diagnosed correctly, UTI’s are easily treated using antibiotics and rarely cause complications. However, the little-known neurological symptoms can result in a misdiagnosis as Alzheimer’s. An elderly person with a UTI is at an increased risk of experiencing delirium, which is characterized by sudden behavioral changes such as confusion, agitation, fatigue, or delusions. Be suspicious of Alzheimer’s-like symptoms if they are accompanied by symptoms of a UTI, which include frequent, painful urination and discolored or foul-smelling urine [27].

9. Sleep disorders

We all know the importance of getting 8 hours of sleep each night, but few of us are aware of just how much sleep depravation can affect our cognitive function. A 1999 study reported that 1 in 5 individuals over the age of 65 experience sleep disturbances, though only a minority seek treatment [28]. Sleep disorders such as sleep apnea, chronic insomnia, and restless leg syndrome can lead to fatigue, difficulty focusing, irritability, and memory loss [29]. These conditions can be easily detected by visiting a sleep clinic.

10. Gluten allergy

This might be the most surprising item on this list: a simple dietary change can completely reverse the symptoms of some people’s dementia. Celiac disease is an allergic reaction to gluten, a protein found in wheat, barley, and rye. Celiac was once believed to be rare, but is now classified as one of the most common autoimmune conditions. The University of Chicago’s Celiac Disease Center estimates that 1 in 133 people have celiac disease, of whom an astounding 97% remain undiagnosed [30]. Though people with celiac can live a healthy life on a gluten-free diet, undiagnosed celiac disease can have serious and even fatal consequences, including progressive dementia and other neurological conditions [31]. For individuals with celiac-induced dementia, switching to a gluten-free diet might completely reverse their symptoms [32].

 

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