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group_1_presentation_1_-_alzheimer_s_disease [2016/09/26 00:14] cunanajk |
group_1_presentation_1_-_alzheimer_s_disease [2018/01/25 15:18] (current) |
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| + | ==========Alzheimer's Disease========= | ||
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| ======Origin and Background====== | ======Origin and Background====== | ||
| - | In 1906, a German psychiatrist and neuropathologist by the name of Alois Alzheimer was drawn to the case of a woman showing unusual symptoms. Post mortem analysis of the brain tissue of the woman, started the journey of Dr. Alzheimer’s description of the neurodegenerative disease (Hippius, 2013). Alzheimer disease is an incurable disorder of cognitive and behavioural impairment with a long and progressive timeline. 75% of patients with dementia are thought to have genetically based Alzheimer’s, however the incidence can also be sporadic (Chapman et al, 2006). In Alzheimer’s, misfolded amino acid aggregates known as plaques develop in brain areas and impact and impede neuronal communication causing brain cell atrophy. This neurodegeneration begins in the hippocampus, then spreads to the rest of the brain over time and increasing severity of the disease. The affected region of the brain is the reduction of the memory encoding hippocampus, along with associated regions of the cerebral cortex involved in thinking, decision making, and planning (Purohit et al, 1998) | + | In 1906, a German psychiatrist and neuropathologist by the name of Alois Alzheimer was drawn to the case of a woman showing unusual symptoms. Post mortem analysis of the brain tissue of the woman started the journey of Dr. Alzheimer’s description of the neurodegenerative disease (Hippius, 2013). Alzheimer disease is an incurable disorder of cognitive and behavioural impairment with a long and progressive timeline. 75% of patients with dementia are thought to have genetically based Alzheimer’s, however the incidence can also be sporadic (Chapman et al, 2006). In Alzheimer’s, misfolded amino acid aggregates known as plaques develop in brain areas and impact and impede neuronal communication causing brain cell atrophy. This neurodegeneration begins in the hippocampus, then spreads to the rest of the brain over time and increasing severity of the disease. The affected region of the brain is the reduction of the memory encoding hippocampus, along with associated regions of the cerebral cortex involved in thinking, decision making, and planning (Purohit et al, 1998) |
| ======Epidemiology====== | ======Epidemiology====== | ||
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| {{:alzchart.jpg|}} | {{:alzchart.jpg|}} | ||
| - | **Figure 1:**This figure shows that dementia has the largest economic burden in the UK, but receives the lowest funding. (Abott, 2011). | + | **Figure 1:**This figure shows that dementia has the largest economic burden in the UK, but receives the lowest funding. (Abbott, 2011). |
| {{:alzdeathcause.jpg|}} | {{:alzdeathcause.jpg|}} | ||
| - | **Figure 2:**This figure shows the leading causes of death by sex (2015).ince Alzheimer's disease is not one of the leading causes of death due to its long course, not as much funding is allocated to it. | + | **Figure 2:**This figure shows the leading causes of death by sex (2015). Since Alzheimer's disease is not one of the leading causes of death due to its long course, not as much funding is allocated to it (Statistics Canada Leading causes of death, by sex (Both sexes) 2015). |
| ===== Symptoms ===== | ===== Symptoms ===== | ||
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| {{:alzbrain.jpg|}} | {{:alzbrain.jpg|}} | ||
| - | **Figure 3:**This figure illustrates the comparison between a pre-clinical and severe Alzheimer's brain. | + | **Figure 3:**This figure illustrates the comparison between a pre-clinical and severe Alzheimer's brain (Neergaard, 2016). |
| ======Disease Progression====== | ======Disease Progression====== | ||
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| {{:alzdiseaserisk.jpg|}} | {{:alzdiseaserisk.jpg|}} | ||
| - | **Figure 5:**This graph shows that the ApoE4 allele is a risk factor for sporadic Alzheimer's disease. It appears that ApoE2 and ApoE3 lower the risk for Alzheimer's disease. | + | **Figure 5:**This graph shows that the ApoE4 allele is a risk factor for sporadic Alzheimer's disease. It appears that ApoE2 and ApoE3 lower the risk for Alzheimer's disease (Kandel et al, 2013). |
| **Familial Cases** | **Familial Cases** | ||
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| - | **Figure 9:** Plaques, neurofibrillary tangles, synaptic and neuronal loss appear in the brain prior to significant cognitive decline. | + | **Figure 9:** Plaques, neurofibrillary tangles, synaptic and neuronal loss appear in the brain prior to significant cognitive decline (Abbott, 2011). |
| ===Technique 1: Physical, neurological and neuropsychological examination=== | ===Technique 1: Physical, neurological and neuropsychological examination=== | ||
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| ===Technique 3- PET=== | ===Technique 3- PET=== | ||
| - | Amyloid plaques can be visualized using Positron Emission Tomography (PET) using a new radioactive compound called Pittsburgh compound B (PIB) that binds with high affinity to amyloid beta or tau (Kandel et al, 2013). PIB is injected into the bloodstream. In Alzheimer’s, PIB is retained specifically in areas with amyloid deposition (Kandel et al, 2013). Other PET labelling agents have been developed to image inflammation as reflected by activated microglia and reactive astrocytes that surround plaques (Kandel, 2013). | + | Amyloid plaques can be visualized using Positron Emission Tomography (PET) using a new radioactive compound called Pittsburgh compound B (PIB) that binds with high affinity to amyloid beta or tau (Kandel et al, 2013). PIB is injected into the bloodstream. In Alzheimer’s, PIB is retained specifically in areas with amyloid deposition (Kandel et al, 2013). Other PET labelling agents have been developed to image inflammation as reflected by activated microglia and reactive astrocytes that surround plaques (Kandel et al, 2013). |
| {{:alzpetpib.jpg|}} | {{:alzpetpib.jpg|}} | ||
| + | |||
| - | **Figure 10:**This image clearly shows PIB retained in brain areas associated with amyloid deposition. There is a lot more PIB in the brain on the right, the Alzheimer's brain, compared with the healthy brain on the left. | + | **Figure 10:**This image clearly shows PIB retained in brain areas associated with amyloid deposition. There is a lot more PIB in the brain on the right, the Alzheimer's brain, compared with the healthy brain on the left (Kandel et al, 2013). |
| ===Technique 4- Fluid Biomarkers=== | ===Technique 4- Fluid Biomarkers=== | ||
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| {{:alzexperimentplot.jpg|}} | {{:alzexperimentplot.jpg|}} | ||
| - | **Figure 11:** Using fluid biomarkers as a method to detect Alzheimer's. On the left, there are lower concentrations of amyloid beta 42 in cerebrospinal fluid compared to the control due to the aggregation of amyloid beta 42. On the right, there are higher concentrations of tau in the cerebrospinal fluid compared to the control, due to the cell death releasing tau. | + | **Figure 11:** Using fluid biomarkers as a method to detect Alzheimer's. On the left, there are lower concentrations of amyloid beta 42 in cerebrospinal fluid compared to the control due to the aggregation of amyloid beta 42. On the right, there are higher concentrations of tau in the cerebrospinal fluid compared to the control, due to the cell death releasing tau (Kandel et al, 2013). |
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| {{:alztreatments.jpg|}} | {{:alztreatments.jpg|}} | ||
| - | **Figure 11:** Table showing treatments according to severity. Image frome Alzheimer's Association, 2016. | + | |
| + | **Figure 12:** Table showing treatments according to severity. Image from Alzheimer's Association, 2016. | ||
| ====Drug Treatment==== | ====Drug Treatment==== | ||
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| {{:alzdrug.jpg|}} | {{:alzdrug.jpg|}} | ||
| - | **Figure 12:** Pharmacodynamics of Solezumab. | + | |
| + | **Figure 13:** Pharmacodynamics of Solezumab. | ||
| Solanezumab is a humanized monoclonal IgG1 antibody that selectively binds to the soluble form of Beta-amyloid (which aggregate and form plaques in the brain) (Farlow et al, 2012). Once this binding occurs, there is a resulting efflux of Beta-amyloid protein peptides away from the Central Nervous System to the blood plasma, ultimately leading to a slowing-down of the progression of the disease. | Solanezumab is a humanized monoclonal IgG1 antibody that selectively binds to the soluble form of Beta-amyloid (which aggregate and form plaques in the brain) (Farlow et al, 2012). Once this binding occurs, there is a resulting efflux of Beta-amyloid protein peptides away from the Central Nervous System to the blood plasma, ultimately leading to a slowing-down of the progression of the disease. | ||
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| - | **The A4 Study (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s)** | + | ===The A4 Study (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s)=== |
| {{:alzpetscan.jpg|}} | {{:alzpetscan.jpg|}} | ||
| - | **Figure 13:** PET scans of the diseased patients. | + | |
| + | **Figure 14:** PET scans of the diseased patients. | ||
| The study is targeted towards individuals between 65-85 years old who are determined to be at risk for AD-related memory loss, but who have not yet significantly shown signs of the disease (Houston, 2015). Thus, this treatment is more of a preventative measure for those at risk. Positron Emission Tomography (PET) scans demonstrate that the Beta-amyloid plaque formation begins about 10-20 years before the initial AD symptoms start to manifest. Therefore, detecting this initial Beta-amyloid overexpression with PET scans in individuals predisposed to Alzheimer’s can then proceed to Solanezumab treatments in order to lower amyloid levels. In addition, it has been hypothesized that the accumulation of the amyloid protein may have a role in the eventual memory loss induced by AD, through an excess production of an abnormal form of the brain protein tau. This abnormal tau forms neurofibrillatory tangles that destroy nervous tissue, therefore propagating brain damage. There appears to be a point in the progression of AD where the removal of Beta-amyloid is not anymore sufficient in reversing or halting the disease development, because a critically high amount of tau has already been generated by this point. Hence, it is also crucial to use PET scans to measure the amount of abnormal tau present in the brain (Houston, 2015). | The study is targeted towards individuals between 65-85 years old who are determined to be at risk for AD-related memory loss, but who have not yet significantly shown signs of the disease (Houston, 2015). Thus, this treatment is more of a preventative measure for those at risk. Positron Emission Tomography (PET) scans demonstrate that the Beta-amyloid plaque formation begins about 10-20 years before the initial AD symptoms start to manifest. Therefore, detecting this initial Beta-amyloid overexpression with PET scans in individuals predisposed to Alzheimer’s can then proceed to Solanezumab treatments in order to lower amyloid levels. In addition, it has been hypothesized that the accumulation of the amyloid protein may have a role in the eventual memory loss induced by AD, through an excess production of an abnormal form of the brain protein tau. This abnormal tau forms neurofibrillatory tangles that destroy nervous tissue, therefore propagating brain damage. There appears to be a point in the progression of AD where the removal of Beta-amyloid is not anymore sufficient in reversing or halting the disease development, because a critically high amount of tau has already been generated by this point. Hence, it is also crucial to use PET scans to measure the amount of abnormal tau present in the brain (Houston, 2015). | ||
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| Mayo Clinic Staff. (2015). Alzheimer's disease. Retrieved September 25, 2016, from http://www.mayoclinic.org/diseases-... | Mayo Clinic Staff. (2015). Alzheimer's disease. Retrieved September 25, 2016, from http://www.mayoclinic.org/diseases-... | ||
| - | Neergaard, L. (2016). Testing brain pacemakers to zap Alzheimer's damage (Update). Medicalxpress.com. Retrieved 21 September 2016, from http://medicalxpress.com/news/2013-01-brain-pacemakers-zap-alzheimer.html (only used an image from here) | + | Neergaard, L. (2016). Testing brain pacemakers to zap Alzheimer's damage (Update). Medicalxpress.com. Retrieved 21 September 2016, from http://medicalxpress.com/news/2013-01-brain-pacemakers-zap-alzheimer.html |
| Patterson, C., Feightner, J., Garcia, A., Hsiung, G., MacKnight, C., & Sadovnick, A. (2008). Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. Canadian Medical Association Journal, 178(5), 548-556. http://dx.doi.org/10.1503/cmaj.0707 | Patterson, C., Feightner, J., Garcia, A., Hsiung, G., MacKnight, C., & Sadovnick, A. (2008). Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. Canadian Medical Association Journal, 178(5), 548-556. http://dx.doi.org/10.1503/cmaj.0707 | ||
