Dementia: Pathology review

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Case Study0:00–1:06

At the neurology department, a 60 year old male, named Oliver, is brought in by his son because lately Oliver has become more aggressive, impolite and he seems to have lost his interest in his family.
Recently, he has also started repeating conversations. Next, there’s a 72 year old female, named Iris, who is also brought by her son.
Iris is always staying at home because she is embarrassed that she’s unable to hold her urine. She also has a hard time finding her things at home because she forgets where she has placed them.
Her son has noticed that she is walking strangely, as if her feet stick to the ground. Finally, there’s a 35-year old male, named Alasdair, who is brought by his partner because in the past few weeks he has started repeating conversations and misplacing their belongings.
Alasdair also has episodes of jerking movements of his left arm and he has fallen twice in the last few days. His medical history reveals corneal transplantation 6 months ago.
Okay, so all of these people have dementia. Dementia occurs when there’s a decline in at least one cognitive function and it impairs daily functioning.

Pathology1:06–1:56

Remember that they need to have intact consciousness. Dementia can result from reversible and irreversible causes.
Reversible causes include alcohol dependence, hypothyroidism, vitamin B12 deficiency, neurosyphilis, normal pressure hydrocephalus, or NPH, and depression.
Irreversible causes include Alzheimer disease, which is by far the most common cause of dementia, vascular dementia, which is the second most common cause, frontotemporal dementia, Lewy body dementia, Parkinson disease, Huntington disease, and Creutzfeldt-Jakob disease, or CJD.
Okay, so let’s take a closer look at the irreversible causes of dementia, starting with Alzheimer disease, which is a very high yield topic for the exams!

Alzheimer disease1:56–6:09

In the cell membrane of a neuron, there’s a molecule called amyloid precursor protein, or APP. Normally, old APP gets chopped up by two enzymes called alpha secretase and gamma secretase to a soluble peptide.
But if another enzyme, called beta secretase, teams up with gamma secretase instead, then the chopped up fragment isn’t soluble, and creates a monomer called amyloid beta.
For the test remember that these amyloid beta monomers bond together outside the neurons, and form beta-amyloid plaques.
These plaques get between the neurons and impair brain function. Also, it’s important to know that amyloid plaque can deposit around blood vessels in the brain, causing amyloid angiopathy, which weakens the walls of the vessels and increases the risk of hemorrhage.
Alright, now neurons are held together by their cytoskeleton, which is partly made up of microtubules, which also form tracks along the cell to ship nutrients and molecules.
A protein called tau makes sure that these tracks don’t break apart. It’s thought that the beta amyloid plaques outside the neuron, initiate pathways inside the neuron that lead to activation of kinase, an enzyme that transfers phosphate groups to the tau protein.
The tau protein stops supporting the microtubules, gets tangled with other tau proteins, forming neurofibrillary tangles inside the neuron.
This makes Alzheimer disease a tauopathy. Okay, so remember, the tangles are found inside the cell, as opposed to the beta-amyloid plaques that are found outside the cells.
Neurons with tangles and non-functioning microtubules can’t function, and end up undergoing apoptosis. The number of neurofibrillary tangles increases as the disease progresses.
In addition, low acetylcholine levels in the nucleus basalis and the hippocampus also contribute to the cognitive symptoms seen in Alzheimer disease.
This is due to impaired activity of an enzyme responsible for acetylcholine synthesis, called choline acetyltransferase in these areas of the brain.
Okay, now Alzheimer disease can be either sporadic or familial. Sporadic is used to describe the late-onset type which is probably a combination of genetic and environmental risk factors, and accounts for the majority of cases.
A gene that’s been identified as possibly contributing is the e4 allele of apolipoprotein E gene, or APOE-e4. Apolipoprotein E helps break down beta-amyloid, but the e4 allele seems to be less effective than the other alleles, meaning patients are more likely to develop beta-amyloid plaques.
Okay, now familial Alzheimer disease is used to describe cases with early onset Alzheimer. This can be caused by several gene mutations, and accounts for about 5 to 10% of cases.
For example, mutations in the PSEN-1 or PSEN-2 genes on chromosome 14 or chromosome 1, respectively, have been linked to early-onset Alzheimer’s.
These genes encode for presenilin-1 and presenilin-2, both protein subunits of gamma-secretase. Mutations in these genes change the location where gamma secretase chops APP, producing different length beta amyloid molecules, which seem to be better at clumping up and forming plaques.
Another known genetic cause of Alzheimer is trisomy 21, or Down syndrome. The gene responsible for producing APP is located on chromosome 21, which means that individuals with Down syndrome have an extra APP gene potentially increasing the amount of amyloid plaque buildup.
Next up is vascular dementia, where there’s a progressive loss of brain function caused by long term poor blood flow to the brain.

Vascular dementia6:09–7:30

Vascular dementia develops when atherosclerosis starts to form in the arteries supplying the brain, like the internal carotid arteries.
This leads to a gradual decrease in blood flow to the brain, which is called chronic ischemia. Sometimes, small parts of the plaques can break away, and can then eventually block a smaller artery, completely stopping the blood supply to the parts of the brain.
Other times, the tiny perforating arteries are affected by atherosclerosis and can get completely blocked off by plaque growing within them.
Regardless of the cause, once blood supply to the brain falls below the demands of the tissue, it’s considered an ischemic stroke.
The tissue damage from an ischemic stroke is usually permanent, and the dead tissue liquefies in a process called liquefactive necrosis.
Brain tissue necrosis leads to a loss of mental functions governed by that area. Now, if another stroke happens later on, more brain tissue might die off, over time this damage gets worse and worse, and the final result is dementia.
This is referred to as multi-infarct dementia and it’s a subtype of vascular dementia that you have to remember for the exams!
Next is frontotemporal dementia. For the test, remember that frontotemporal dementia refers to atrophy of the frontal lobes that eventually progresses to the temporal lobes, with relative sparing of the parietal and occipital lobes.

Frontotemporal dementia7:30–8:52

A high-yield subtype of frontotemporal dementia is Pick disease, which is characterized by the presence of Pick bodies, which are tangles of tau proteins.
Tau comes in different isoforms, like the 3R and the 4R isoforms. In Pick disease, 3R isoforms get hyperphosphorylated, change shape and stop being able to tie together the microtubules in the neuron's cytoskeleton.
They also start clumping together, forming tangles. So Pick disease is a tauopathy, like Alzheimer disease.
A key difference is that the tangles in Pick disease, are called Pick bodies, and they’re only made up of the 3R isoforms, whereas the neurofibrillary tangles in Alzheimer disease are made up of both 3R and 4R tau isoforms.
Now, neurons with loads of tangles and non-functioning microtubules don't function well, and the neurons undergo apoptosis.
Okay, now next is Lewy body dementia. The underlying cause of Lewy body dementia isn’t well understood.

Lewy body dementia8:52–9:43

Normally, neurons contain a protein called alpha synuclein, and in Lewy body dementia, this protein get misfolded within the neurons.
The misfolded alpha-synuclein aggregates to form Lewy bodies that deposit inside neurons, particularly in the cortex and the substantia nigra.
Under a microscope, Lewy bodies look like dark, eosinophilic inclusions inside the affected neurons. As the disease progresses, more and more neurons accumulate Lewy bodies and die.
The significance of Lewy bodies, however, is unknown, but remember that they’re also seen in other diseases like Parkinson disease.Alright, now Parkinson disease can also cause dementia.
This is a slowly progressive genetic disorder that primarily affects individuals over 50 years old. It’s characterized by the loss of dopamine-producing, or dopaminergic, neurons in the substantia nigra, which is a part of the basal ganglia.

Parkinson disease9:43–10:24

Normally, within the basal ganglia there’s a balance between dopamine, which promotes movement, and acetylcholine, which inhibits movement.
In Parkinson disease, the loss of dopaminergic neurons, results in less movement, difficulties in speech and swallowing, as well as cognitive symptoms, like dementia in the later stages of the disease.
Next, there’s Huntington disease, which is very high yield! So, Huntington disease is an autosomal dominant neurodegenerative disorder that typically affects individuals around 40 years of age.

Huntington disease10:24–12:40

It is caused by a mutation in the Huntington disease, or HD, gene on chromosome 4. This gene contains a CAG trinucleotide repeat, which encode for the amino acid glutamine, The gene encodes for a protein called huntingtin.
The mutated protein aggregates within the neuronal cells of the caudate and putamen of the basal ganglia, causing neuronal cell death.
So, the caudate and the putamen of the basal ganglia are the areas of the brain affected in Huntington disease. The brain regions affected by Huntington disease have decreased GABA and acetylcholine and increased dopamine levels.
There’s also excessive activation of a subtype of glutamate receptors, called NMDA receptors, that leads to glutamate excitotoxicity, a process by which neurons are damaged.
Over time, if enough neurons die in the caudate and putamen, which together form the dorsal striatum, this can cause actual loss of brain tissue volume in these areas, which can expand to the lateral ventricles.
These areas of the brain play an important role in movement, particularly, inhibiting it, and that’s why Huntington disease causes movement problems like chorea and athetosis.
But they also have cognitive symptoms, like dementia. Alright, now another high yield concept about Huntington disease is a phenomenon called anticipation, which is where there’s an increased number of trinucleotide repeats in subsequent generations.
This leads to an earlier onset and more severe presentation of the disease. This process of adding more repeats is called repeat expansion.
It happens way more in the production of sperm than eggs, and so anticipation generally occurs when the biological father is the affected parent.
Finally, a rare cause of dementia is Creutzfeldt-Jakob disease, or CJD. CJD is the most common cause of spongiform encephalopathy and it’s a high yield topic for the exams!

Creutzfeldt-Jakob disease12:40–15:26

Spongiform encephalopathy refers to a group of neurodegenerative diseases caused by the accumulation of infectious, misfolded prion proteins, called prions.
Misfolded means that they change from having mostly α-helices to having a lot of ß pleated-sheets and so, they become resistant to being broken down by proteases.
When a misfolded prion protein enters the neuron, it induces the misfolding of the normal prion proteins found inside the neuron.
As a result, prions accumulate within the neuron and trigger apoptosis with the help of an intracellular 14-3-3 protein.
When large numbers of neurons die, the brain gets replaced by cysts making it look like a sponge. That’s why these diseases are called spongiform encephalopathies.
Now, there are actually four types of CJD; familial or fCJD, variant or vCJD, iatrogenic or iCJD, and sporadic or sCJD. Familial Creutzfeldt-Jakob disease occurs when there’s a mutation in the PRNP gene which encodes for the prion protein.
Variant Creutzfeldt-Jakob disease is caused by eating the meat of cows with prions in the muscle tissue. In cows, these prions cause bovine spongiform encephalopathy, which is more commonly called “Mad cow disease.” When sheep are fed cow meat, the prion causes the disease Scrapie.
If a person eats the meat of affected cows or sheep, the prions get absorbed through the intestines into the bloodstream.
The protein can somehow get through the blood brain barrier and then enters neurons by a process called adsorptive endocytosis.
Adsorptive endocytosis is a process where the plasma membrane of nerve cells folds inwards to bring in substances that otherwise would not be able to cross the plasma membrane by themselves.
Iatrogenic Creutzfeldt Jakob disease is caused by medical procedures, like a corneal transplant, where the transplanted organ or the instruments gets contaminated by prions.
Finally, there’s sporadic Creutzfeldt-Jakob disease which pops up in populations randomly without a clear cause. Now let’s quickly go over the reversible causes of dementia.

Normal pressure hydrocephalus15:26–16:27

Common ones include chronic alcohol use, hypothyroidism, vitamin B12 deficiency, or tertiary syphilis. Another important reversible cause is depression, and cognitive impairment due to depression is referred to as pseudodementia.
A key finding in pseudodementia is that individuals are often anxious about their memory impairment as opposed to other causes of dementia, like Alzheimer disease.
A very high yield reversible cause of dementia is normal pressure hydrocephalus, or NPH. NPH typically occurs in the elderly so it’s often misdiagnosed as Alzheimer disease.
It’s caused by abnormal venous drainage of the cerebrospinal fluid, resulting in hydrocephalus. Since the frontal lobe is the most affected, Individuals with NPH usually present with urinary incontinence and gait disturbance at first, and then dementia.Alright, now let’s switch gears and talk about clinical presentation.

Symptoms16:27–25:31

Although all these disorders can cause dementia, many of them also cause other symptoms that will be key clues for the correct diagnosis.
But before that, let’s take a look at how dementia typically presents. Most of the time, a close family member or friend notices the individual’s change in cognition.
This includes impaired memory, which leads to repeating conversations or misplacing belongings. Language impairment can make it hard to think of common words.
Additionally, concentration and executive function are impaired, so individuals have a hard time with complex tasks, like managing their finances.
Visuospatial impairment can prevent them from recognizing faces and navigating in familiar locations. Sometimes, family members also notice changes in the individual’s personality.
Okay, now there are specific symptoms that can help you identify the different causes of dementia. For the exams remember that Alzheimer disease has an insidious onset and gradual progression.
Individuals usually go through 3 phases. First is the asymptomatic phase.
Second is a predementia phase called mild cognitive impairment, during which there’s gradual onset of memory impairment without much impairment in other cognitive domains, and no impairment in daily functioning.
This differs from normal aging, because the memory impairment is greater than expected for the individual’s age. The third phase is the dementia phase, and that’s where individuals develop more significant memory loss, followed by slow, gradual loss of the other cognitive functions, such as language, visuospatial, and executive functions.
Now, there are two main types of memory: episodic memory, which is memory of events, and semantic memory, which memory of words and vocabulary.
Early on, episodic memory is impaired and semantic memory remains intact. Later on, both episodic and semantic memory get impaired.
Episodic memory can be subclassified into immediate, recent, or long term. Immediate memory is sometimes called procedural memory, and it’s the memory that you use to repeat back a phone number right away.
Recent memory is the memory you use to remember a list of three words five minutes later, like those 3 words from earlier.
This is the type of memory that’s impaired early on in Alzheimer disease because the disease affects the hippocampus first, which is responsible for recent memory.
Long-term memory is the memory of events that have occured years ago, and these are not impaired until late in the course of this disease.
For example, an individual with Alzheimer may remember the details of their wedding 50 years ago, but they won’t be able to remember where they were yesterday.
Okay, now symptoms of vascular dementia vary depending on which region of the brain is damaged. For example, if someone has strokes in the temporal lobe, it might be difficult for them to remember things or make new memories.
Someone with a stroke in the left parietal lobe might lose the ability to speak, which is called an aphasia. But then if they get another stroke in the frontal lobe, their personality might begin to change.
One thing that’s constant, is that the symptoms of dementia appear suddenly and brain function decreases with each stroke.
Another characteristic finding in vascular dementia is that individuals have neurological deficits which correspond to the region of the brain that’s affected by the stroke.
They can also have other manifestations of atherosclerosis, like coronary artery disease, and other comorbidities that increase the risk of stroke like hypertension and diabetes.
Now, in multi-infarct dementia, there’s a characteristic stepwise decline in cognitive function. For example, the individual develops a stroke, and as a consequence demonstrates a sudden decline in their memory.
Then, in between stroke events, there is no progression of their cognitive dysfunction, until another stroke occurs, and they suddenly lose another cognitive domain such as language, and so on.
This pattern, alongside a temporal relation to the stroke, is what differentiates it from Alzheimer disease where the decline in cognitive function is steady and gradual.
Also, unlike in Alzheimer disease where recent memory is usually lost first, the pattern of cognitive decline in vascular dementia varies depending on which area was infarcted.
Individuals with frontotemporal dementia usually present before the age of 65 and it is very important to remember for the test that early on they have behavioral symptoms, with relative sparing of memory defects.
These symptoms include personality changes, impaired judgement, apathy and disinhibition. They also have perceptual-motor function loss, meaning individuals struggle with things like hand-eye coordination or body-eye coordination.
There are two variants of frontotemporal dementia. In the behavioral variant, first there are three or more of the following five symptoms: disinhibition; apathy or inertia; loss of sympathy or empathy; stereotyped, compulsive or ritualistic behavior; hyperorality which when people put inappropriate objects in their mouth, and dietary changes.
And second, there is a decline either in social cognition or in executive abilities which are a set of skills necessary to adapt to the environment and to achieve goals.
The language variant is when there’s a prominent decline in language skills, or aphasia. Individuals have difficulty in speech production, word finding, object naming, grammar, or word comprehension.
Okay, now two very similar types of irreversible dementia syndromes are Lewy body dementia and Parkinson disease dementia.
Both include dementia and “parkinsonism”, a term used to describe the movement disorder in both diseases. The symptoms of parkinsonism can be remembered with the mnemonic “TRAP”.
“T” for tremor, “R” for rigidity, “A” for akinesia or bradykinesia, which is absence or slowness of movement, and “P” is for postural instability.
Lewy body dementia is distinct from dementia secondary to Parkinson disease in that the onset of dementia occurs before the onset of motor symptoms, and this takes place less than one year apart.
In Parkinson disease, motor symptoms develop first and it can take many years before the onset of dementia. Other features of Lewy body dementia include recurrent episodes of having vivid visual hallucinations, and fluctuating, episodic deficits in attention and alertness, which may be confused with delirium.
In addition, individuals with Lewy body dementia can have sleep behavior disorder, where individuals move a lot while sleeping.
Okay, now, in contrast to parkinsonism, individuals with Huntington disease often have chorea, which are involuntary, random, rapid, dance-like movements, or athetosis, which are slower, writhing, “snake-like” movements that mainly affect the hands.
They can also have psychiatric symptoms like depression, psychosis or aggressive behavior. Death usually occurs within 10–20 years of diagnosis, often by aspiration pneumonia, on account of discoordinated swallowing, or by suicide.
Now, for the test remember that individuals with CJD has a long incubation period but after the onset of symptoms individuals develop rapidly progressive dementia within weeks to months.
It is also classically associated with ataxia, which is defined as lack of coordination of voluntary movements and myoclonus, a jerking movement of a muscle group.
Hiccups are an example of myoclonus. In CJD, the myoclonus is usually generalized and can be triggered when the person is startled, and that’s why it’s referred to as “startle myoclonus”.
CJD eventually leads to death since there’s currently no cure. Finally, for NPH, remember that it affects the elderly and symptoms can appear over a month and presents with dementia, urinary incontinence and gait disturbance.
Their gait is described as “magnetic”, because it seems like the person’s feet are glued to the ground. Alright, now let’s move on to diagnosis.

Diagnosis25:31–32:34

The Montreal cognitive assessment, or MOCA, or the mini-mental status examination, or MMSE, can be done to assess orientation, registration, recall, attention, and language.
For your exams, it’s helpful to remember how each of these cognitive domains is assessed. For example, orientation is assessed by asking individual what time it is, where they are, or who the president is.
Registration is assessed telling the individual three words, like dog, table, and cake, and then asking them to repeat it immediately.
Then, they’re asked to repeat those three names five minutes later, which assesses recall, or short term memory. Long term memory is assessed by asking the individual details about significant events in his life, for example date of marriage.
Attention, or concentration, can be assessed by asking the individual to spell a word backwards or recite the months of the year backwards.
Language is tested by asking the individual to name presented objects or repeating a phrase. Additionally, individuals are asked to obey a command written on a piece of paper, such as “pick up the pen on the table”.
Comprehension is assessed by asking the individual to follow a 3-step command such as: “take this paper, fold it in half, and place it on the table”.
Finally, individuals are asked to write a sentence and copy an illustration, such as a pentagon. The MMSE totals to 30 points, and a score of less than 24 implies cognitive impairment, which may suggest or delirium or dementia.
A very high yield concept is how to differentiate the two. Delirium is usually acute in onset, lasts only a couple of hours to days, and the cognitive symptoms fluctuate, meaning they come and go.
On the other hand, dementia is usually gradual in onset, lasts months to years, and the cognitive symptoms usually progress over time.
Also, consciousness and awareness are always impaired in delirium. However, they are only impaired in the later stages of dementia.
Additionally, delirium always occurs as a direct physiological consequence in the event of an acute insult, such as an infection, electrolyte imbalance, change in medication or intoxication or due to a psychiatric condition, like schizophrenia or depression.Alright, now after the diagnosis of dementia is made, it’s important to find out if the cause of dementia is reversible so treatment can be started before permanent damage occurs.
So, it’s helpful to send off TSH levels for hypothyroidism, vitamin B12 levels to assess for a deficiency, and a rapid plasma reagin test, or RPR for syphilis.
For NPH, a brain MRI shows ventriculomegaly of all the ventricles, a patent cerebral aqueduct, and no signs of cortical atrophy.
As suggested from the name, a lumbar puncture will show a normal opening pressure. Okay, now onto the irreversible causes of dementia.
The presumptive diagnosis of Alzheimer disease is made clinically and investigations are done to exclude other causes of dementia.
For your exams, it’s important to know that even in the early stages, a brain CT or MRI can show hippocampal atrophy that can progress to diffuse cortical atrophy.
As the brain atrophies, or shrinks, and the gyri get narrower, the sulci get wider and the ventricles get larger. Enlargement of the ventricles due to brain atrophy is referred to as “ex vacuo ventriculomegaly”.
A brain biopsy, showing extracellular amyloid plaques that stain with Congo red and intracellular neurofibrillary tangles, is the only investigation that would definitively diagnose Alzheimer disease.
But that isn’t usually done until there’s an autopsy after death. Vascular dementia can be diagnosed using brain imaging, most commonly CT or MRI, which will show multiple cortical and subcortical infarcts and changes like atrophy of the brain cortex, confirming the ischemia.Diagnosis of frontotemporal dementia is also based on a brain CT or MRI of the brain which shows atrophy of the frontal and temporal lobes with narrower gyri, wider sulci and ex vacuo ventriculomegaly.
The parietal and occipital lobes are typically spared. Diagnosis of Lewy body dementia is based on the pattern of symptoms.
Onset of dementia less than one year after parkinsonism, along with vivid visual hallucinations, indicates Lewy body dementia.
But the diagnosis of Lewy body dementia can only be confirmed with a brain autopsy that shows Lewy bodies in neurons. Now, to diagnose Parkinson disease dementia you first need to diagnose Parkinson disease.
This requires the presence of bradykinesia in addition to another one of the “TRAP” symptoms, and ruling out other potential causes.
However, the diagnosis can be confirmed with a brain autopsy that shows Lewy bodies in neurons, like in Lewy body dementia, and also the presence of depigmented dopaminergic neurons in the substantia nigra.
Huntington disease should be suspected in an individual around 40 years of age with dementia, movement disorders like chorea and athetosis, and psychiatric symptoms.
The combination of these features in a young individual can be mistaken for substance abuse. Family history of a first-degree relative with Huntington disease is a very important clue.
The diagnosis is confirmed using polymerase chain reaction of the HD gene, which shows the CAG repeats. MRI imaging of the brain characteristically shows atrophy of the caudate and putamen and ex vacuo ventriculomegaly.
On a brain MRI, CJD classically shows enhancement of the basal ganglia and thalamus. An EEG shows periodic bursts of high-voltage sharp waves.
The combination of the clinical presentation and these investigations is usually sufficient to diagnose CJD. If a lumbar puncture is done, there may be elevation of protein 14-3-3.
Ultimately, the definitive diagnosis of spongiform encephalopathy is done after a person dies with a brain biopsy. Brain biopsy shows intracytoplasmic vacuoles that transform into cysts giving the characteristic spongy appearance of the grey matter.
Okay, now let’s discuss treatment. The good news is that reversible causes can be treated and the dementia will usually go away.

Treatment32:34–36:44

Alcohol dependence can be treated with medications like acamprosate, disulfiram, and naltrexone. Hypothyroidism can be treated with thyroid hormone replacement, vitamin B12 deficiency is treated with vitamin B12 supplementation, and syphilis is treated with penicillin.
The treatment for NPH is placing a ventriculoperitoneal shunt, which drains the excess cerebrospinal fluid. However, although placement of a ventriculoperitoneal shunt helps improve walking, it doesn’t always improve cognition.
Now, about the irreversible causes, low acetylcholine levels contribute to Alzheimer disease and so cholinesterase inhibitors like donepezil, rivastigmine and galantamine can be used for treatment since they increase cholinergic transmission at the synaptic cleft.
In individuals that can’t tolerate cholinesterase inhibitors, NMDA-receptor antagonists, like memantine can be used. These medications don’t slow the progression of the disease, but they do help mitigate some of the cognitive and behavioral symptoms like forgetting family members or personal info, making day-to-day life relatively easier for affected individuals.
Finally, depression is common in all types of dementia but especially in Alzheimer disease, and selective-serotonin reuptake inhibitors, or SSRIs, are an effective treatment option for behavioral symptoms, although they don’t improve cognition.
Unfortunately, there is no available treatment that can help reverse vascular dementia. Instead, treatment mainly focuses on preventing another stroke from happening.
This includes blood pressure, diabetes and cholesterol control, lifestyle modification; such as exercise, dietary changes, and smoking cessation, as well as starting antiplatelet agents like aspirin.
In vascular dementia, the evidence is mixed for the cholinesterase inhibitors, but they are often prescribed because of the frequent co-occurrence of cerebrovascular and neurodegenerative disease.There is no current treatment available that will help delay the progression of frontotemporal dementia.
However, selective-serotonin reuptake inhibitors can help with the behavioural symptoms, and atypical antipsychotics can be used for psychosis.
Okay, now in Lewy body dementia, treatment is aimed at alleviating motor symptoms. These symptoms respond to drugs used to treat Parkinson disease like levodopa, a dopamine agonists.
However, individuals with Lewy body dementia are “dopamine-sensitive”, meaning that dopamine agonists can cause them to have hallucinations, agitation, and confusion.This unique reaction is also a clue that the person has Lewy body dementia.
Also, although it might be intuitive to give antipsychotics like haloperidol or risperidone for the visual hallucinations, these medications should be avoided in Lewy body dementia as they can worsen parkinsonism.Now, for Parkinson disease dementia, rivastigmine, which is a cholinesterase inhibitor used for Alzheimer disease, is approved along with the medications used for Parkinson disease like carbidopa-levodopa and dopamine agonists like pramipexole and ropinirole.
These will help motor symptoms but will not reverse or slow the course of the disease.As for Huntington disease, there’s no treatment that affects overall survival.
However, medications that decrease dopamine levels, like the neuroleptics, which are dopamine receptor antagonists, and tetrabenazine, which depletes dopamine, are used to treat chorea.
Unfortunately, there is no current treatment for CJD and so prevention of transmission is the key management strategy of the disease.
All right, as a quick recap! Dementia occurs when there’s a decline in a cognitive domain like memory, language or executive function, causing impairment in daily functioning.

Review36:44–37:45

Dementia can result from reversible causes like alcohol dependence, hypothyroidism, vitamin B12 deficiency, neurosyphilis, and NPH.
But it usually results from irreversible causes such as Alzheimer disease, which is by far the most common cause of dementia, vascular dementia, frontotemporal dementia, Parkinson disease dementia, Lewy body dementia, Huntington disease, and Creutzfeldt-Jakob disease.
Dementia can be diagnosed based upon symptoms, clinical tests like the Montreal cognitive assessment, or the mini-mental status examination.
The causes can be identified by symptoms specific to the disease, imaging tests like brain CT or MRI, and more definitive tests like a brain biopsy during autopsy.
Now, back to the patients! Okay, so Oliver, due to his age and history of behavioral symptoms with relative sparing of memory, most likely has frontotemporal dementia.

Summary37:45–38:39

Diagnosis can be confirmed with a brain CT or MRI showing atrophy of the frontal and temporal lobes. Now, Iris has the characteristic triad of NPH, urinary incontinence, “magnetic gait” and dementia.
Brain MRI will show enlarged ventricles with no signs of cortical atrophy. Also, a lumbar puncture will reveal normal opening pressure.
Fortunately, NPH can usually be reversed by placing a ventriculoperitoneal shunt. Finally, due to Alasdair’s young age, history of rapidly developing dementia along with myoclonus and ataxia, and history of corneal transplantation, Alasdair most likely has iatrogenic