Category Archives: Aging

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

 

 

Driving Under the Influence of Parkinson’s

“Have you ever noticed that anybody driving slower than you is an idiot, and anyone going faster than you is a maniac?” George Carlin

“If all the cars in the United States were placed end to end, it would probably be Labor Day Weekend.” Doug Larson

The Dilemma: At some age in our life, maybe, just maybe, we could lose the privilege of driving our car/truck.  If you are living with Parkinson’s, depending on the individual, losing the legal right to drive your motor vehicle might/could happen at an even earlier age.  A discussion of driving under the influence of Parkinson’s is presented here.

“I love driving cars, looking at them, cleaning and washing and shining them. I clean ’em inside and outside. I’m very touchy about cars. I don’t want anybody leaning on them or closing the door too hard, know what I mean?” Scott Baio

The Michon model of normal driving behavior:  In 1985, Michon proposed that drivers need to conduct problem-solving while driving; he divided it  into three levels of skill and control. The model includes strategic (planning), tactical (maneuvering), and operational (control) levels.   When you think about it driving really is a complicated task.   The strategic level is basically the general route and planning needed to successfully navigate the motor vehicle.  The tactical and control levels involve the individual driving circumstances and how one responds and our responsiveness to the action of driving.   And of course, it’s quite obvious, that unsafe driving is operating a motor vehicle in an unsafe manner regardless of your health status. Driving safely is important for the individual as well as for the people around you; thus, it is a serious task to evaluate someone’s competency to drive a motor vehicle. Shown below is a schematic drawing of the Michon model of normal driving behavior.

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“The one thing that unites all human beings, regardless of age, gender, religion, economic status, or ethnic background, is that, deep down inside, we all believe that we are above-average drivers.” Dave Barry

Decision-making while driving:   Below are some traffic signs that we might encounter in our usual driving pattern depending on where we live. When you think about decision-making you’re in your lane you’re driving down the road and you see signs like this, then what?  You can see how it takes all three levels of driving competency to navigate successfully while driving a motor vehicle in a complex maneuver.  Now add the complications of someone with Parkinson’s, you may need to re-think the entire situation. What this says is that when you’re driving a motor vehicle you’re trying to integrate many levels of sensory, motor and cortical function to the process. In Parkinson’s, we may have some sort of motor skill/task impairment, potentially mixed with a minor cognitive disorder, and further clouded by traditional drug therapy. Who makes the decision for the patient with Parkinson’s about being able to continue to drive?  Not an easy answer.

“Some beautiful paths can’t be discovered without getting lost.” Erol Ozan

 Possible problems that could occur while driving with Parkinson’s: The control or operational level of driving a car can be influenced by motor defects experienced by many with Parkinson’s, including rigidity, tremor, bradykinesia and dyskinesia. Futhermore, non-motor deficits could impair both route planning, strategic and tactical levels, and these would include cognitive decline, neuropsychiatric symptoms and/or visual impairment. And on top of that in the elderly population, many people with Parkinson’s have additional co-morbidity that could also contribute to diminish our ability to drive a motor vehicle. Thinking about just one aspect, slowness in cognitive function, the inability to make a decision quickly could lead to poor performance time and might affect driving in someone with Parkinson’s. Alternatively, you may have none of these problems and will be driving for many more years. But as we all start to exhibit signs and symptoms of motor and non-motor deficits, this will eventually become an important issue for each of us to deal with at some point in time.

“Always focus on the front windshield and not the review mirror.” Colin Powell

 What are some criteria for determining our fitness to drive a motor vehicle when you have Parkinson’s? In a very nice review, Jitkritsadakul and Bhidayasiri suggest there are five different red flags that should tell our neurologist that we may have an impairment that should limit our driving of motor vehicles. First, these include our clinical history, which would be a history of accidents, sleeping attacks while driving and combined with the daily dose amount of levodopa. Next would be a questionnaire to determine our level of daily sleepiness. Third, a motor assessment skills test. Fourth, a cognitive assessment. And fifth would be a visual assessment.  Look above at the Michon driving schematic and think about the three levels of skill required for driving and substitute someone with Parkinson’s and how that could diminish one or more of the skill sets over time.  What this says to me is that through a combination of family and friends and carepartner,  along with the advice of our neurologist, one should be able to make a critical assessment of whether or not we should continue to drive.

“Driving your car through deep pools of flood water is a great way of making your car unreliable. Smart people turn around and avoid it.” Steven Magee

A love of motor vehicles (a personal expression):  I grew up loving automobiles; and living on Air Force Bases, I saw many different types of sports cars  (e.g., Corvette, Jaguar, Triumph, Porsche, Shelby Mustang, Ferrari- you just had to believe that Air Force pilots live for speed in the air and their cars showed it on the ground). I can remember in 1964 (I was 11 years old) going to the Ford dealership with my dad to see the very first Ford Mustang cars; thinking how beautiful they were and remembering my dad’s comment that was a lot of car for $2,400.   I still have vivid memories of riding with my dad (yes, he was a former pilot) in his ~1962 white Porsche. I can still remember in 1971 getting my first car, a 1968 Chevrolet Camaro (red interior and red exterior) with standard transmission (three on the floor) and powered by a 327 cubic inch V-8 engine. [Please note, the pictures below are representative images because I could not find any actual old photos of these cars]

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Over the decades, I can recall the weekly car-washing sessions, typically on Saturday mornings. With the exception of one car in the early 1980’s, I have loved and truly enjoyed the automobiles I’ve driven.  Like many people I’ve named all my cars; my two current automobiles are named Raven and Portia. I still enjoy driving a standard shift car using the clutch that requires both cognitive function and motor skills to navigate the automobile. I have always thought “It’s going to be a cold day in hell before they take my car away”; however, it’s a reality in the future I now face with Parkinson’s. In fact one of the very first people I ever told about my Parkinson’s several years ago, the very first question she asked me was “Are you still able to drive?”  In summary, driving under the influence of Parkinson’s is something we all will need to consider with time; I wish you well with your driving experiences.

“Driving a car provides a person with a rush of dopamine in the brain, which hormonal induced salience spurs modalities of creative and critical thinking regarding philosophical concepts such as truth, logical necessity, possibility, impossibility, chance, and contingency.” Kilroy J. Oldster

https://www.ncbi.nlm.nih.gov/pubmed/27729986

1.    Jitkritsadakul O, Bhidayasiri R. Physicians’ role in the determination of fitness to drive in patients with Parkinson’s disease: systematic review of the assessment tools and a call for national guidelines. Journal of Clinical Movement Disorders. 2016;3(1):14. doi: 10.1186/s40734-016-0043-x.

Cover photo credit: s-media-cache-ak0.pinimg.com/564x/22/d1/75/22d175ac53a0a5dbb04e77ae52a49c52.jpg

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Parkinson’s Awareness Month: Veterans Health Administration PD Video Series

“My motto was always to keep swinging. Whether I was in a slump or feeling badly or having trouble off the field, the only thing to do was keep swinging.” Hank Aaron

“Nothing worth having comes easy.” Theodore Roosevelt

Introduction: Several years ago, the Veterans Health Administration produced videos to educate/inform our veterans about Parkinson’s disease.   For more information, read about the VA Core Values and Mission Statement (click here); it is an admirable sentiment.

As we are living longer, so too are our veterans. Some service-related-experiences may have predisposed some of them to develop Parkinson’s.  All of these videos are available on YouTube.  However, since this is Parkinson’s awareness month, putting them all together might benefit others to better understand Parkinson’s.   I definitely learned something from watching these videos, they were all outstanding.

Each individual video features a veteran (frequently their care-partner too) who agreed to be videotaped (having done this type of interview myself, it is not an easy experience); I admire their courage to participate and to help educate all of us. Furthermore, the VA clinical and support staff were passionate and compassionate about their roles in dealing with our veterans with Parkinson’s.

“Losing the possibility of something is the exact same thing as losing hope and without hope nothing can survive.” Mark Z. Danielewski

Veterans Health Administration – My Parkinson’s Story:
My Parkinson’s Story:
Early Parkinson’s Disease [click here for video]

My Parkinson’s Story: Thinking and Memory Problems with Parkinson Disease [click here for video]

My Parkinson’s Story: Medications [click here for video] 

My Parkinson’s Story: Dyskinesias [click here for video] 

My Parkinson’s Story: Atypical [click here for video] 

My Parkinson’s Story: Driving [click here for video]

My Parkinson’s Story: Sleep Problems and Parkinson’s Disease [click here for video] 

My Parkinson’s Story: Genetics [click here for video] 

My Parkinson’s Story: Exercise [click here for video] 

My Parkinson’s Story: Environmental Exposure [click here for video]

My Parkinson’s Story: The Impact of Depression in Parkinson’s Disease [click here for video] 

My Parkinson’s Story: Impact of Falls and Parkinson’s Disease [click here for video]

My Parkinson’s Story: The Caregiver [click here for video] 

My Parkinson’s Story: Deep Brain Stimulation and Parkinson Disease [click here for video]

My Parkinson’s Story: Hospitalization [click here for video] 

My Parkinson’s Story: Speech and Swallowing [click here for video] 

My Parkinson’s Story: Advanced Parkinsons [click here for video]

“Not I, nor anyone else can travel that road for you. You must travel it by yourself. It is not far. It is within reach. Perhaps you have been on it since you were born, and did not know. Perhaps it is everywhere – on water and land.” Walt Whitman

“We can’t equate spending on veterans with spending on defense. Our strength is not just in the size of our defense budget, but in the size of our hearts, in the size of our gratitude for their sacrifice. And that’s not just measured in words or gestures.” Jennifer Granholm

Cover Photo Credit: http://wallpapersafari.com/w/Fy0h6Q/

Science of Advanced Age as a Risk Factor for Parkinson’s

“Spring passes and one remembers one’s innocence.
Summer passes and one remembers one’s exuberance.
Autumn passes and one remembers one’s reverence.
Winter passes and one remembers one’s perseverance.”
Yoko Ono

“Embrace aging.” Mitch Albom, Tuesdays with Morrie

Précis: The great majority of individuals with Parkinson’s reveal no genetic mutations, no past history of head injury, no prior exposure to pesticides/toxins, or any family history of the disorder.  Public health studies have consistently shown that advanced age is an adverse risk factor for developing Parkinson’s. The average age of Parkinson’s onset is ~60 years of age. Presented here is a brief overview about why advanced age is a major risk factor for Parkinson’s.

Parkinson’s and advanced age as a risk factor: Parkinson’s is a neurodegenerative disorder that affects movement. It starts slowly, usually a small tremor or stiffness in a hand. With time, Parkinson’s progresses; typically characterized by motor symptoms such as slowness of movement (bradykinesia) with rigidity, resting tremor (Parkinsonian tremor), balance and walking problems, and difficulty swallowing and talking. Parkinson’s has several non-motor symptoms including anxiety, depression, and insomnia (just to mention a few).

Following Alzheimer’s, Parkinson’s is the second most common neurodegenerative disorder affecting ~0.3% of the developed world population. Interestingly, the incidence of Parkinson’s increases to 3% for persons >65 years old, which strongly indicates that advanced age is a major risk factor for this disorder.

Aging can promote several detrimental events that damage the dopamine-producing neurons in the substantia nigra.  These pathological events accumulate and weakens the ability of these neurons to respond to further insults, which ultimately leads to Parkinson’s (see below).

The left-side of the composite picture below could be entitled “40 years of Frank (in my 20’s, 30’s, 50’s and 60’s).”  The title of the right-side of the composite picture could be “Somehow the neurons in my substantia nigra (top right) are making very little dopamine (chemical structure bottom right); thus, I have Parkinson’s.”

Frank+40yrs“As long as I am breathing, in my eyes, I am just beginning.” Criss Jami

Age of the U.S. population: Andy Rooney once said “It’s paradoxical that the idea of living a long life appeals to everyone, but the idea of getting old doesn’t appeal to anyone.”  As the table below shows, by each successive decade of life, females outlive males. However, between 2000 and 2010, the U.S. male population grew at a slightly faster rate than the female population. By contrast, mortality rates in older men differ from older women, where the census results showed that women tend to live longer than men.  A further breakdown shows the 65 to 69 year old age group grew by 30%; this age group represents the leading edge of the Baby Boomers who started turning 65 in 2011 (The Baby Boom includes people born from mid-1946 to 1964). We are living longer; when coupled with advanced age as a risk factor for Parkinson’s, this implies an increasing burden on health care systems to deal with this disorder.

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“Wisdom comes with winters.” Oscar Wilde

Science behind advanced age as an adverse risk factor for Parkinson’s:  Pat Benatar said this about aging, “I’ve enjoyed every age I’ve been, and each has had its own individual merit. Every laugh line, every scar, is a badge I wear to show I’ve been present, the inner rings of my personal tree trunk that I display proudly for all to see. Nowadays, I don’t want a “perfect” face and body; I want to wear the life I’ve lived.”  Advanced age contributes to many different diseases whether from a loss of organ function with time, diminished immune surveillance capacity, or the inability to remove naturally-accumulating toxic substances by the host defense mechanisms (just to describe a few of many possible outcomes of advancing age).

In evaluating a large group of elderly people without Parkinson’s (750 individuals with an average age of 88.5 years), it was noted that ~1/3 showed mild to severe substantia nigra neuronal cell loss. Thus, natural advanced aging results in some loss to the dopamine-producing substantia nigra mid-brain region. But what shifts the balance that leads to Parkinson’s in some individuals?  Reeve et al. (2014), in an outstanding article, reviewed the science behind why advancing age is the biggest risk factor for Parkinson’s.  They suggest three processes occur in the substantia nigra that ultimately leads to Parkinson’s: (1) detrimental changes to the microenvironment; (2) dysfunction of the subcellular organelles called mitochondria; and (3) disruption in the process of protein degradation (the drawing below highlights these processes).

Aging.SN(1) Detrimental changes to the substantia nigra microenvironment:  As an analogy, over time, with extended use and re-use, your laptop slows down and ultimately begins little processor-derived-hiccups-of-dysfunction.  As we age, some changes occur in the dopamine-producing neurons of the substantia nigra; these include increased oxidative stress, changes in calcium-neuron properties, modification of iron-neuron interactions, and accumulation of the pigment called neuromelanin.  Processing of dopamine in the substantia nigra generates detrimental oxidative stress; which is made worse due to an age-related reduction of a protein named the dopamine transporter (DAT). The DAT escorts dopamine from neuron-to-neuron to reduce oxidative stress. Calcium helps maintain dopamine levels; and sustained transport of calcium into the cell is detrimental to the energy-producing organelle, the mitochondria.  Iron is an essential element; however with age, iron accumulates to contribute to the oxidative stress. Neuromelanin is responsible for the color of the substantia nigra.  Evidently, neuromelanin accumulates with age; in contrast to the other factors mentioned above, neuromelanin may be neuroprotective.

(2) Dysfunction of the subcellular organelles called mitochondria:  As an analogy, over time, you charge the battery of many devices like your cell phone, laptop/tablet, toothbrush, and beard trimmer; eventually no matter what you do, slowly but surely these devices lose their charge.  Likewise, mitochondria are subcellular power factories that can become dysfunctional (and lose energy) with advancing age. The mitochondrial respiratory system (electron transport) is a major cellular energy producer; and it consists of five protein complexes named respiratory complexes I–V. Several mitochondria electron transport complexes are modified/inhibited with age, leading to a loss of mitochondria-derived energy. Inhibiting complex I (reduced NADH dehydrogenase–ubiquinone oxidoreductase) causes Parkinsonian-like symptoms; furthermore loss of complex IV (cytochrome c oxidase) promotes a respiratory deficiency. This leads to the reduction of energy production (ATP molecules), which would negatively impact “neuronal excitability” (engaging/activating the neuron). Linked to this energy drain is mutation of mitochondria DNA, causing further detriment to these dopamine-producing neurons. These mutations ultimately reduce mitochondria function and activity, which promotes the accumulation of mis-folded proteins (a very bad thing). A key disease-causing feature of Parkinson’s is the build-up and denaturation of the protein named alpha-synuclein (think of the changes of frying an egg, which goes from clear to cloudy-opaque as the heat cooks and denatures the egg proteins). Accumulation of alpha-synuclein protein aggregates advances further mitochondria impairment.

(3) Disruption in the process of protein degradation:  As an analogy, shaving with a new razor blade leads to complete cutting-off of the hair; however, over time, as the razor blade dulls you end-up with more and more uncut hair. Similarly, we use enzymes called proteases and they are somewhat like a razor blade; their goal is to cut-up (digest) proteins.  Proteases are used in many different biological settings (e.g., digestion of food, clotting of blood); in the substantia nigra, proteases help eliminate protein debris as a means of self-renewal of the neurons.  There are two types of protease processes that cut and remove accumulating damaged proteins (like alpha-synuclein aggregates); they are named the ubiquitin proteasome system and autophagy.  Due to their complex biology, neither the ubiquitin proteasome system nor autophagy will be further described here; suffice it to say that if both protease systems are diminished this will further impair mitochondria.  These checks-and-balances are lost with advanced aging, which leads to a concert of adverse events where an individual could develop Parkinson’s.

“There is a fountain of youth: it is your mind, your talents, the creativity you bring to your life and the lives of people you love. When you learn to tap this source, you will truly have defeated age.” Sophia Loren

A symphony combining (1) + (2) + (3) from above + advancing age = risk of developing Parkinson’s: The natural-biology of dopamine-producing neurons leads to declining function with advanced aging. The detrimental process of reactive oxygen species initiates a symphony of badness that leads to neuronal cell dysfunction/death. The larghetto first movement leads to the reduction of the DAT, accumulation of neuromelanin, increased iron deposits, and disruption of calcium transport. The next movement is fortissimo with mutation of mitochondria DNA, inhibition of complex I and complex IV to reduce both ATP levels and neuronal excitability; these events lead to the acquisition of other mitochondria defects. The cadenza results in the beginning phase of aggregating alpha-synuclein, which contributes to substantia nigra dysfunction.  In the final movement of our symphony, we reach a crescendo where toxic levels of aggregating alpha-synuclein accumulate that cannot be cut/removed by the protein degradation pathways. The symphony ends with substantial stress to the dopamine-producing neurons in the substantia nigra to eventually promote neuronal cell death, which results in Parkinson’s.  With advancing age, most individuals will stop at the end of the first movement (microenvironment changes to substantia nigra); while others will complete the entire symphony over-and-over again to develop Parkinson’s.

“Age has no reality except in the physical world. The essence of a human being is resistant to the passage of time. Our inner lives are eternal, which is to say that our spirits remain as youthful and vigorous as when we were in full bloom. Think of love as a state of grace, not the means to anything, but the alpha and omega. An end in itself.” Gabriel García Márquez, Love in the Time of Cholera

References Cited:
Reeve, A., et al, Ageing and Parkinson’s disease: Why is advancing age the biggest risk factor?, Ageing Research Reviews, Volume 14, March 2014, Pages 19-30, http://dx.doi.org/10.1016/j.arr.2014.01.004.

Abdullah, R., et al., Parkinson’s disease and age: The obvious but largely unexplored link, Experimental Gerontology, Volume 68, August 2015, Pages 33-38, http://dx.doi.org/10.1016/j.exger.2014.09.014.

Petralia, R.S. , et al., Communication breakdown: The impact of ageing on synapse structure, Ageing Research Reviews, Volume 14, March 2014, Pages 31-42, http://dx.doi.org/10.1016/j.arr.2014.01.003.

Mhyre, Timothy R. et al. Parkinson’s Disease. Sub-cellular biochemistry 65 (2012): 389–455. PMC. Web. 9 Nov. 2015.  doi:  10.1007/978-94-007-5416-4_16  PMCID: PMC4372387