Category Archives: Dementia

Diet and Dementia (Cognitive Decline) in the Aging

“When diet is wrong medicine is of no use. When diet is correct medicine is of no need.’’ Ancient Ayurvedic Proverb

‘‘What is food to one man may be fierce poison to others.’’ Lucretius (99 B.C.-55 BC).

Précis: Last month in London, England, at the Alzheimer’s Association International Conference (AAIC) 2017, there were several presentations focused on diet and the link with dementia/cognitive decline in the elderly population.  Two reports described the effect of specific diets [Mediterranean, DASH (Dietary Approaches to Stop Hypertension), MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay), and NPDP (Nordic Prudent Dietary Pattern)] to maintain cognitive function in the aging population. In another study, the MIND diet was shown to reduce dementia in the women from the Women’s Health Initiative Memory Study (WHIMS).  Finally, it was shown that either the absence or excess of certain vitamins, minerals and other key nutrients could promote neuro-inflammation, which would be detrimental to the brain. This post reviews elements of these presentations.

“One should eat to live, not live to eat.” Moliere

A Healthy Body and Brain Combine Diet, Life-style, and Attitude: It is easy to say what it takes to be healthy; however, approaching/achieving/accomplishing it takes a concerted effort. In a minimal sense, achieving a healthy body and brain unites an efficient diet, an effective lifestyle, and a positive attitude.  Thus, a healthy body and brain requires a collective approach to living properly (and it helps to have good genes).

“Take care of your body. It’s the only place you have to live.” Jim Rohn

Inflammation and Parkinson’s: One of the many suggested causes of Parkinson’s is neuro-inflammation (see figure below).  The impact of diet promoting inflammation and cognitive decline in the aging population got my interest.  The combination of eating too much of ‘bad’ foodstuff with too little of some ‘good’ food components somehow promotes neuro-inflammation that contributes to the development of dementia. If the goal of my blog is related to Parkinson’s, what is the goal of this particular post? To present the notion that detrimental effects of neuro-inflammation could diminish brain function. And it’s this ‘possibility’ that makes the story relevant to this blog because neuro-inflammation is linked to the development of both Alzheimer’s and Parkinson’s.  Therefore, the specific pathway to how you develop that inflammation of the brain is relevant and an important topic.

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“Tell me what you eat, and I will tell you who you are.” Jean Anthelme Brillat-Savarin

Diet Linked to Neuro-inflammation: There’s an old phrase “You Are What You Eat”, which simply means it’s critical to eat good food in order to stay healthy and fit. Building on solid evidence that eating well is brain healthy, researchers are beginning to explore mechanisms through which dietary mechanisms may influence cognitive status and dementia risk. Dr. Gu and colleagues (Columbia University, New York) examined whether an inflammation-related nutrient pattern (INP) was associated with changes in cognitive function and structural changes in the brain. Gu, Y., et al. (An Inflammatory Nutrient Pattern Is Associated Both Structural and Cognitive Measures of Brain Aging in the Elderly) presented a follow-up study to earlier work using brain scans (MRI) combined with levels of inflammatory makers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and cognitive function studies of >300 community-dwelling elderly people who were non-demented.

They created what was termed an “InflammatioN-related Pattern (INP) where increased levels of CRP and IL-6 were found in participants with low dietary intake of omega-3 polyunsaturated fatty acids, calcium, folate and several water- and fat-soluble vitamins (including B1, B2, B5, B6, D, and E) and increased consumption of cholesterol, beta-carotene and lutein. The INP was derived from a 61-item food frequency questionnaire that the study participants answered about their food intake during the past year. Study participants with this ‘INP-diet-pattern’ also had poorer executive function scores and smaller total brain gray matter volume compared to study participants with a healthier diet.  The strength of the study was the scientific precision and methodology; however, it was not directly comparing one diet to another.  Further studies are needed to verify the role of diet to induce neuro-inflammation-related changes in dementia (cognitive health).  Furthermore, mechanistic insight is needed to understand how a diet with either an absence or an excess of certain nutritional components promotes neuro-inflammation to alter brain function and structure. Their results imply that a poor diet promotes dementia and smaller brain volume in the aging brain through a neuro-inflammatory process.

“The food you eat can either be the safest and most powerful form of medicine, or the slowest form of poison.” Ann Wigmore

What is Good for Your Heart is Good for Your Brain: The Mediterranean diet, a diet of a type traditional in Mediterranean countries, characterized especially by a high consumption of vegetables and olive oil and moderate consumption of protein, is usually thought to confer healthy-heart benefits. The DASH (Dietary Approaches to Stop Hypertension) diet was developed to help improve cardiovascular health, especially hypertension. The DASH diet is simple: eat more fruits, vegetables, and low-fat dairy foods; cut back on foods that are high in saturated fat, cholesterol, and trans fats; eat more whole-grain foods, fish, poultry, and nuts; and limit sodium, sweets, sugary drinks, and red meats. Neurologists have merged the two diets, creating the Mediterranean-DASH Intervention for Neurodegenerative Delay, or MIND diet; testing the hypothesis that if it’s good for the heart it will be good for the brain.   The MIND diet is gaining attention for its potential positive effects on preserving cognitive function and reducing dementia risk in older individuals. In an earlier study, Morris et al. (Alzheimer’s Dement. 2015; 11:1015-22) found that  individuals on the MIND diet showed less cognitive decline as they aged.

Moving to 2017, Dr. McEvoy and colleagues (University of California, San Francisco) studied ~6000 older adults in the Health and Retirement Study. They showed that the study participants who followed either the MIND or the Mediterranean diets were more likely to maintain strong cognitive function in old age (McEvoy, C., et al. Neuroprotective Dietary Patterns Are Associated with Better Cognitive Performance in Older US Adults: The Health and Retirement Study). Their results also showed that study participants with either of these healthier diets had significant retention of cognitive function.

The doctor of the future will no longer treat the human frame with drugs, but rather will cure and prevent disease with nutrition.” Thomas A. Edison

The Nordic Prudent Dietary Pattern (NPDP) Protects Cognitive Function: The NPDP includes both more frequent and less frequent food consumption categories: More frequent consumption of non-root vegetables, apple/pears/peaches, pasta/rice, poultry, fish, vegetable oils, tea and water, and light to moderate wine intake; Less frequent intake of root vegetables, refined grains/cereals, butter/margarine, sugar/sweets/pastries, and fruit juice. Dr. Xu and colleagues (Karolinska Institute, Stockholm, Sweden) studied the relationship of diet to cognitive function in >2,200 dementia-free community-dwelling adults in Sweden (Xu,W., et al. Which Dietary Index May Predict Preserved Cognitive Function in Nordic Older Adults). During six years of evaluation, they reported that study participants with moderate loyalty to the NPDP had better cognitive function compared to study participants who deviated more frequently from the NPDP.  The scientists noted that, in the Scandinavian population studied, the NPDP was better at maintaining cognitive function compared to other diets (Mediterranean, MIND, DASH, and Baltic Sea).

“The trouble with always trying to preserve the health of the body is that it is so difficult to do without destroying the health of the mind.” Gilbert K. Chesterton

Women on the MIND Diet are Less Likely to Develop Dementia: Dr. Hayden and colleagues (Wake Forest School of Medicine, Winston-Salem, North Carolina) studied diet and dementia in >7,000 participants from the Women’s Health Initiative Memory Study (WHIMS) (Hayden, K., et al. The Mind Diet and Incident Dementia, Findings from the Women’s Health Initiative Memory Study).   The study showed that older women who followed the MIND diet were less likely to develop dementia. These results were obtained by stratification of the WHIMS  participants from very likely to very unlikely to adhere to the MIND diet; they were  assessed for almost 10 years.  Their results imply that it may not require drastic diet changes to help preserve the aging brain.

“It’s not about eating healthy to lose weight. It’s about eating healthy to feel good.” Demi Lovato

Diet and Dementia in the Aging Brain: Four different studies with similar results; diet can  influence dementia and cognitive function in the aging brain.  The single most important finding in these studies was simply that a good diet helps maintain a healthy brain. Strong evidence was presented in three of the studies that the Mediterranean, the MIND and NPBP are excellent diets to help maintain cognitive function as we age.  Mechanistic studies to further demonstrate the link of dietary components with an increase in neuro-inflammation  would be most interesting. A confounding issue is that overall health and a healthy brain are more than just diet alone.  To reduce the chance of cognitive decline and dementia, it’s important to remember as we get older to protect our brain by eating well, exercise regularly, and exercise our brain by becoming lifelong learners (see Word Cloud below).

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“The older I get, the more vegetables I eat. I can’t stress that more. Eating healthy really affects my work. You not only need to be physically prepared, but mentally and spiritually.” James Badge Dale

 Cover photo credit:  C.J. Reuland

 

 

Treatment of Parkinson’s Psychosis with Nuplazid

“At what point do you give up – decide enough is enough? There is only one answer really. Never.” Tabitha Suzuma

“Be proud of your scars. They remind you that you have the will to live.” Paulo Coelho

Précis: ~50% of the people with Parkinson’s develop psychotic tendencies. Treatment of their psychosis can be relatively difficult. However, a new drug named Nuplazid™ was just approved by the FDA specifically designed to treat Parkinson’s psychosis. A brief review follows.

Psychosis in Parkinson’s (Hallucinations and Delusions): Psychosis can occur in ~50% of Parkinson’s patients. The Parkinson’s psychosis typically results in hallucinations (where you see or hear things that are not there) and/or delusions (where you have false beliefs). As one could imagine, hallucinations and delusions would be severe/serious aspects of this disorder.  Parkinson’s psychosis requires treatment because these symptoms are life-altering; they lead to an imbalanced emotional status, and they would disrupt interactions with loved ones and others.

“Severe mental illness like psychosis can lead to a tragedy like this – that people can see things that aren’t real and hear things that aren’t real and believe things that aren’t real, and act in that distorted reality.” Andrea Yates

Antipsychotic Drugs (APD) Typically Target Dopamine Receptors: There are many antipsychotic (neuroleptic) drugs available. Historically, most of these drugs target neurotransmitters that regulate nerve cell communications. Blocking the neurotransmitter dopamine is thought important to managing symptoms of psychosis. Modern pharmacology has not only expanded the drugs available, but many years of research has expanded the ‘targets’ for antipsychotic drugs (ADP).

The usual targets for most APD’s include dopamine receptors, serotonin receptors and other monoamine receptors (see figure below).  Therefore, if you are being treated for both Parkinson’s disease and Parkinson’s psychosis you can immediately see the ‘problem’. You likely take some form/mimic of dopamine to manage the movement disorder; at the same time, you could be blocking dopamine receptors with an APD being used to manage the Parkinson’s psychosis. This would likely create an antagonistic medication/treatment-relationship in managing the disorder.

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“He wrote on a piece of paper with his pencil. Psychosis: out of touch with reality. Since then, I have been trying to find out what reality is, so that I can touch it.” Jeanette Winterson

“New-Kid-on-the-Block” (Nuplazid™) to Treat Parkinson’s Psychosis: The US FDA has approved Nuplazid (pimavanserin), the first APD of its kind to treat the hallucinations and delusions associated with Parkinson’s psychosis. Nuplazid is being marketed by Acadia Pharmaceuticals Inc. of San Diego, California (click here for more detailed information about Nuplazid). Nuplazid was given breakthrough therapy designation and priority review by the FDA (click here to read the FDA news release); the goal was to help relieve symptoms in Parkinson’s psychosis.

Unlike other APD’s that have broader target sites, as depicted in the figure above, Nuplazid is a selective inverse agonist that targets 5-HT2 serotonin receptors. What is an ‘inverse agonist’?  A slight diversion into pharmacology says that “an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist.” (click here to read more). For a visual depiction on how an inverse agonist works as a drug, see the drawing below.

Inverse_agonist_3.svg

Nuplazid Offers New Hope: Using Nuplazid to treat Parkinson’s psychosis should have no negative impact on motor symptoms that need treatment in Parkinson’s. Michael S. Okun, MD, Medical Director of The National Parkinson Foundation, said last month: “Today’s approval of Nuplazid represents a major paradigm shift in the treatment of Parkinson’s disease psychosis. Through its novel and selective mechanism of action, Nuplazid is a breakthrough treatment that works in a whole new way— treating hallucinations and delusions without blocking dopamine receptors and, therefore, not impairing motor function in Parkinson’s psychosis patients.”  Thus, Nuplazid is both a first step and a new approach for managing the symptoms of Parkinson’s psychosis. Only time will tell if Nuplazid is a hopeful beginning for treating Parkinson’s psychosis.

“If we want to cultivate hopefulness, we have to be willing to be flexible and demonstrate perseverance. Not every goal will look and feel the same. Tolerance for disappointment, determination, and a belief in self are the heart of hope.” Brené Brown

Cover image credit: http://www.fyiaonly.com/wp-content/uploads/2014/06/Great-Smoky-Mountains.jpg

Inverse agonist figure credit: https://upload.wikimedia.org/wikipedia/commons/6/6c/Inverse_agonist_3.svg

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Parkinson’s and Dementia: Remembering Robin Williams (1951-2014)

“No matter what people tell you, words and ideas can change the world.” Robin Williams

Hiding behind the initial diagnosis: When I was diagnosed with Parkinson’s 18 months ago, I told my immediate family, a few close friends, and some key people in my research group.  Receiving news that you have a progressive neurodegenerative disorder strikes hard in your world and will re-define your life priorities.  Mostly, I kept the news to myself.  At first I didn’t want to believe it; thinking that there was no way the dopamine agonist would make a difference (so very wrong!).  Partly, I was worried either of pity or of prejudice.  In reality since going public and accepting the diagnosis, I have received only incredible and lasting support.

Acceptance of the Parkinson’s diagnosis brings clarity, which allows you to challenge this sinister and slowly evolving disorder. You are ready to keep living by reinforcing your emotional well-being, by enhancing your physical strength, by renewing your life-forward strategy, and by staying hopeful, wholehearted, mindful, persistent and positive.

“Sometimes the questions are complicated and the answers are simple.”  Dr. Seuss

Remembering Robin Williams (1951-2014):  A year ago this month, the world heard the incredibly sad news of Robin Williams’ suicide. We each have our own favorite memories of his genius, whether it was comedy or drama; there was only one Robin Williams.

“Comedy is acting out optimism.” Robin Williams

Parkinson’s and Robin Williams: We also heard that three years earlier he had been diagnosed with Parkinson’s; he had kept the diagnosis a secret. It was revealed in a pathologist’s report that he also had something termed ‘diffuse Lewy body dementia’ in his brain. Parkinson’s affects your mid-brain region that controls movement.  By contrast, dementia with Lewy bodies affects your brain in different areas that regulate vision and it leads to spatial-awareness problems, nightmares and hallucinations.  Thus, It is possible that Robin Williams had both Parkinson’s and dementia with Lewy bodies.

“I believe in destiny. There must be a reason that I am as I am. There must be.” Robin Williams

Parkinson’s and dementia: Parkinson’s usually presents as a movement disorder. The most common symptoms of Parkinson’s include rigidity; slowness of movement (bradykinesis); postural instability and gait problems; and resting tremor. There is also another side to Parkinson’s that includes cognitive dysfunction, depression and dementia (dementia definition: a persistent mental disorder with memory losses, personality changes, and impaired reasoning).  It is estimated that >50% of those with Parkinson’s will eventually develop Parkinson’s-related dementia.  This could be a subtle cognitive problem expressed mainly as an executive dysfunction (executive function allows you to manage time, pay attention, plan and organize, remember details, and do things based on your experience).  In a subset of people, it progresses to dementia, which is a progressive executive dysfunctional syndrome with attention deficit, fluctuating cognition, and some have psychotic symptoms.

“Make your life spectacular, I know I did.” Robin Williams

Lewy bodies, Parkinson’s and dementia with Lewy bodies (DLB): A culprit in the development of Parkinson’s is accumulation of the protein alpha-synuclein. These aggregated protein deposits in brain neurons are called Lewy bodies [for more information see: https://journeywithparkinsons.com/2015/05/23/the-alpha-synuclein-story-in-parkinsons/ ; https://journeywithparkinsons.com/2015/06/21/of-mice-and-men-endogenous-alpha-synuclein-contributes-to-mitochondria-inhibition-in-parkinsons/https://journeywithparkinsons.com/2015/06/10/a-comparison-of-parkinsons-to-alzheimers/ ]. In Parkinson’s, Lewy bodies accumulate in neurons of the mid-brain substantia nigra, which substantially reduces dopamine production. Loss of dopamine-producing neurons leads to the movement disorder found in Parkinson’s.

Lewy bodies in other regions of the brain can result in DLB. Some of the key clinical manifestations of DLB are progressive cognitive decline, alertness and attention changes, visual hallucinations, and motor symptoms consistent with Parkinson’s.  We know that Lewy bodies are found in the brains of people with Parkinson’s. The occurrence of Lewy bodies in DLB implies that DLB is somehow related to Parkinson’s.  This further indicates that someone could have Parkinson’s and DLB.

Thank you Robin Williams for showing the world that one man can make a difference in the lives of millions, while still fighting his own personal demons. You are missed, but never forgotten.” Steven Wolff

Dementia, the ‘dark side of the force’ of Parkinson’s:  There is no silver-lining to Parkinson’s but there is substantial hope.  Managing the movement disorder is possible with sustained effort and a positive approach to life. Cognitive changes add complexity to living with this disorder; tackle these changes with all your might.  Adding dementia to the progression brings a new dimension of severity to Parkinson’s.  Your proactive/protective shields are your cherished loved ones, family and friends.  Their love, help and hope will allow you to sustain your grasp on this insidious disorder.  As always, you still matter a lot; focus on the mounting challenge, and stay you.

We don’t read and write poetry because it’s cute. We read and write poetry because we are members of the human race. And the human race is filled with passion. And medicine, law, business, engineering – these are noble pursuits and necessary to sustain life. But poetry, beauty, romance, love – these are what we stay alive for.” Robin Williams