It’s 7am. I wake up full of excitement. I’m 9 years old and today I’m going to have my first Christmas. I slip out of bed. The floor is icy so I dance on edge of balls of my feet to the door. Outside a snowstorm is in full swing. I make it to the plush hallway carpet and scrunch my toes through the fluffy fibers with relief. I hear noise downstairs and excitement soars through me: time for presents!
My grandmother was still driving at 87. She loved to shop, she loved clothes, she loved to die her hair pink and she loved to fret over her grandchildren especially when they made the trip “across the pond” to Baltimore from the Emerald Isle. She has been cooking since before the sun came up and the house smells like fresh pine, butter, bread and chicken.
Fast forward about 8 years. We haven’t seen my grandmother in 4 years. She can no longer drive and getting up the two flights of stairs to her bedroom is becoming very difficult. Her face is far more blank. So easy to laugh before and full of feminine grace, she now looks perpetually startled. She frets more now but not in the exasperated and playful way she did before. She’s more fearful now. Her steps and mannerisms once elegant and soft are now jilted and stiff.
Over the next few years, she would forget almost everything, everything except how my grandfather used to take her crab fishing. He spent years teasing memories out of her and them on a date going crabbing in a little boat was the one she always remembered.
What is Dementia?
Dementia is characterized by progressive cognitive disturbances leading to a loss of independent function. The cells of the brain become more and more damaged making it harder and harder for them to communicate. Depending on which parts of the brain are affected and how much damage there is, a person will experience a different symptom profile. As degradation of the cells continues, these symptoms worsen. It isn’t a disease but rather a word used to refer to a set of symptoms common to many disorders. Symptoms include a combination of Memory problems, impaired communication, reduced focus, cognitive reasoning and judgement disturbances and issues with visual perception.
Alzheimer’s disease accounts for 60 to 80% of dementia cases and vascular dementia is the second most common dementia type at about 10% of cases. Lewy body dementias is sometimes cited as the second most common but while misdiagnosed as Alzheimer’s or Parkinson’s Disease is thought to occur, incidence numbers are limited with our best current guess being 4% of cases at a minimum (Van Jones and O’Brien, 2013).Dementia can in some cases be reversible, such as symptoms caused by thyroid issues or vitamin deficiencies.
Types of Dementia
| Types of Dementia | A Brief Description |
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Memory problems and behavioural changes followed by reduced mobility, confusion, disorientation, and issues with speech, swallowing and judgement. Characterized by beta-amyloid protein plaque, tau protein tangles and neuronal damage/death. |
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Impaired decision making, planning and judgment skills. Caused by vascular blockage or damage that trigger bleeding in the brain or strokes. |
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Restricted movement, tremors and speech difficulties. Characterized by alpha-synuclein clumps thought to cause neuronal degradation. |
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Symptoms similar to AD and PD, memory loss, problems with thinking, sleep disturbances, hallucinations and restricted movement. |
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A more than one type of dementia presenting together. |
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Personality and behavioral changes and language difficulties. Characterization depends on subtype. |
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Rapid and fatal memory and coordination loss with behavioural changes. Characterized by misfolded proteins in the brain. |
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Urinary incontinence and walking and memory issues. Triggered by excess fluid in the brain. |
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Mood changes, abnormal involuntary movements and impaired reasoning and thinking. Caused by a defective gene on chromosome 4. |
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Severe memory issues. Caused by severe deficiency of vitamin B-1, usually due to alcohol misuse. |
We’ll go more into some of these in future articles.
What Causes Dementia?
Short answer: unless stated in the table above, we don’t know.
Long answer: we have some theories. Let’s focus on AD for simplicity. Previously, we looked at the role of microglia in Alzheimer’s and how furthering our understanding of their role in the disease may lead to new treatment options. Here, we’ll look more generally at some theories as to how AD may begin.
Theory #1: The (historically) most popular theory
Since a defining feature of AD are amyloid plaques, attributing the disease to beta-amyloid protein is a long held theory. A misfolded protein, called a “prion”, can trigger other proteins to misfold. This infection-like spread of defective proteins is known as the “Prion Theory” of AD. These proteins are chemically “sticky” so they can clump together and form knots called plaques. Small clumps are thought to block cell to cell signalling and trigger an inflammatory immune response. This response is thought to damage surrounding tissue. A brain that’s on fire with trigger-happy inflammatory cells will have an ever-growing number of damaged cells that in turn further provoke an immune response. It’s a vicious, neurodegenerative cycle.
Theory #2: The (historically) second most popular theory
The other major played in AD being the tau protein tangles, these guys also get blamed. Within cells, structural proteins called microtubules are a component of the cytoskeleton. They play a key role in many fundamental features of a cell: division, ciliary and flagellar motility, internal organization and intracellular transport. Sound important right?! Well the proteins that support these fibers in the Central Nervous System, is tau (along with another protein, tubulin). In AD, these proteins become defective (probably due to excessive or abnormal phosphorylation, protease activity or exposure to polyanions) and can no longer support the microtubules. The microtubules collapse leading to tangles. I’ll leave you to think what the implications of this are for the poor cell involved but here is a clue: RIP cells.
Theory #3: A new contender
With both theory #1 and #2, while they sound promising, the major flaw is that it isn’t clear what starts the process of the proteins going haywire. Over the last decade, modulating the immune system as a form of treatment has become a very in vogue idea across many disorders and conditions from cancer to autoimmunity to allergy. Since neuroinflammation is seen in AD, the idea that perhaps immunodysregulation is to blame is the most recent theory as to what may trigger AD. Recently, a group at Harvard published research showing that beta-amyloid protein may not be the bad guy after all. They showed the beneficial role it plays in mice and worms in combating bacterial and fungal infections. They proposed that the beta-amyloid may actually be playing a protective role by surrounding the pathogens (remember those plaques?) and that drugs that target this protein may leave whatever triggered the immune system to go into overdrive to ramp up its attack and provoke an even more powerful immune response. Yikes. We’ll have to see if this proves true in humans or not though before theory #1 loses any street cred. Afterall, if I had a dollar for every time we’ve cured something in mice, I’d be retired in Hawaii by now.
If you’re like me, you’re probably wondering: well what causes the inflammation in the first place? A combination of genetics and insults to the CNS (injury, toxins, pathogens) may be to blame but right now, it isn’t clear.
Share your thoughts in the comments.
