Aging/neurodegeneration Flashcards
Why do we expect more people suffering from dementia in the future?
Because of demographic changes, mainly caused by the large baby boomer generation.
Rank these by which are the best for dementia prevention: Education Stop smoking Avoid high blood pressure prevent obesity and diabetes Prevent depression Social interaction
- Education
- Stop smoking
- Social interaction
- prevent depression
- Avoid high blood pressure
- prevent obesity and diabetes
However, for degenerative dementia such as Alzheimer’s, these factors don’t seem to help in prevention.
What is a typical psychometric test of Alzheimer’s?
Test persons are asked to draw a clock that shows a specific time of day. Depending on the irregularities of the clock drawing (misplaced numbers, missing arrows etc.), the clinician can score the patient, indicating a probability of having AD.
What are the first signs of dementia in the brain?
The first brain areas to be affected are in the temporal lobe, where the hippocampus degenerates, why memory problems arise, often accompanied by language problems.
Amyloid hypothesis of AD.
The amyloid hypothesis postulates that amyloid-beta (Aβ), in a variety of forms, triggers a cascade harming synapses and ultimately neurons, producing the pathological presentations of Aβ plaques, tau tangles, synapse loss and neurodegeneration, leading to dementia.
Baptist Vs Taoists
Chicken/egg problem, what comes first: dysfunction of Beta-amyloid-protein or disturbed protein metabolism?
Baptists are the ones who believe that AD is initially caused by the dysfunction of Beta-amyloid-protein. They believe that AD is a disturbance of amyloid metabolism that lead to amyloid deposits, leading to inflammation and tangles (plaques).
Taoists Believe that the underlying cause of AD is a disturbance in axonal transport leading to disturbed protein metabolism beyond just amyloid. However, they also hold that amyloid plaques are to blame for AD, they just disagree on the root cause.
Mouse studies have shown that tau-protein does not spread in the brain without the presence of amyloid, underscoring the importance of amyloid.
Hypothetical biomarker model of AD
In a big meta analysis of clinical AD studies, a hypothesis was proposed saying that AD is dependent on Amyloid beta proteins and amyloid plaques, which leads to an increase of tau proteins. This causes atrophy and clinical symptoms.
However, the risk-level and the clinical symptoms that arise from the biomarker abnormalities are dependent on genetic factors and neuroplasticity as well.
Subjective Cognitive Decline (SCD)
Cognitive deficits that cannot be measured clinically, but are observed in the preclinical phase of Alzheimer’s Disease, where the patient self-reports e.g. memory deficits.
What is Apoe4?
An gene that codes for the production of Apolipoprotein E4 or just Apoe4. Apoe4 is the main genetic risk factor for AD. 25% of people carry a copy of the gene. 90% of people over 90 years old with a copy of the Apoe4 gene suffers from AD.
It leads to earlier formations of amyloid plaques in the brain, with a 40% chance at 50 years old (Although not showing clinical symptoms this early). If amyloid placques are discovered early, it makes sense to remove amyloid from the brain in order to avoid neurodegeneration.
AT(N) system for Preclinical AD diagnosis
A= Amyloid T= Tau-Pathology N= Neurodegeneration
A model for determining whether a person has AD, based on the presence or absence of amyloid, tau and neurodegeneration. A person is only considered to suffer from AD if both amyloid and tau are present.
Amyloid and tau can be measured by cerebrospinal fluid tap. Studies have shown that CSF biomarkers can predict AD, supporting the AT(n) system.
MRI-volumetry
Analyzing the size of brain areas, compared to healthy individual. In AD, hippocampus is clearly decreased in volume or disappeared entirely. These signs can already be seen during mild cognitive impairment (MCI).
How is amyloid measured in the brain?
Using the tracer Florbetaben in PET-imaging, amyloid levels in the brain can be measured, and the risk of having AD can be predicted with very high accuracy.
How and why is glucose measured in the brain?
Using PET-imaging, fluor glucose levels can be measured in the brain. This reveals reduced glucose metabolism in the brain, and can be used to distinguish Alzheimer’s disease from frontotemporal dementia.
What is Aducanumab?
AD medication consisting of giving antibodies that interfere with the disturbed amyloid metabolism and thereby modifies the disease by reducing amyloid plaques from the brain. Aducanumab has shown a dose dependent response, with the highest doses removing the most amyloid from the brain in the course of a year. Similarly, the severity of the disease has been shown to decrease with Aducanumab treatment, which more or less confirms the amyloid hypothesis of AD.
The drug was approved by the FDA in a controversial manner, where most experts from the FDA advisory board voted against the approval, and when it was fast-tracked despite their protests, it led to a group resignation.
Dementia with Lewy bodies
Dementia with Lewy bodies (DLB), is the second most common type of progressive dementia after Alzheimer’s disease. Protein deposits, called Lewy bodies, develop in nerve cells in the brain regions involved in thinking, memory and movement (motor control).
DLB causes a progressive decline in mental abilities. People with DLB might have visual hallucinations and changes in alertness and attention. Other effects include Parkinson’s disease signs and symptoms such as rigid muscles, slow movement, walking difficulty and tremors.
When clinically distinguishing between AD and BLD, visual hallucinations is a clear marker for BLD
