Alzheimers Disease.pdf

ALZHEIMER’S Amani Altahaineh Leen Alkhatib Qusai Al - Shurbaji Hamza Al - Sabbagh Moath Abo Rumman Adam almghareez Abdalsame almomani Deia alkhateeb  What is Alzheimer? Alzheimer's disease is a brain disorder that gets worse over time. It is characterized by changes in the brain, that l...

ALZHEIMER’S Amani Altahaineh Leen Alkhatib Qusai Al - Shurbaji Hamza Al - Sabbagh Moath Abo Rumman Adam almghareez Abdalsame almomani Deia alkhateeb  What is Alzheimer? Alzheimer's disease is a brain disorder that gets worse over time. It is characterized by changes in the brain, that lead to the deposit of some proteins, which causes the brain to shrink and eventually die. AD is the most common cause of dementia; It is a gradual deterioration in memory, thinking ability, behavioral and social skills. These changes can affect a person's ability to function. Genetic Basis Alzheimer’s Disease (AD) is primarily characterized by its genetic heterogeneity. It can be classified into two main types based 1.Early-Onset on theDisease Alzheimer’s genetic (EOAD):mechanisms involved: Monogenic: Mutations in three key genes are known to cause EOAD. These include: APP (Amyloid Precursor Protein): Mutations happen on chromosome 21, and can lead to abnormal processing of the protein, resulting in increased production of amyloid-beta peptides. PSEN1 (Presenilin 1) and PSEN2 (Presenilin 2): PSEN1 mutation happens on chromosomee 14, while PSEN2 mutation occurs on the first chromosome. Mutations in these genes affect the gamma-secretase complex, leading to the abnormal cleavage of APP and increased amyloid- beta production. These mutations follow an autosomal dominant inheritance pattern. 2.Late-Onset Alzheimer’s Disease (LOAD): Polygenic: LOAD is influenced by multiple genes and their interactions with environmental factors. The most significant genetic risk factor is the APOE (Apolipoprotein E) gene, specifically the APOE ε4 allele. Other genes associated with LOAD include TREM2, SORL1, and CLU. Pathophysiology The pathophysiology of Alzheimer’s Disease involves multiple molecular mechanisms and biological processes, leading to neuronal dysfunction and brain pathology: 1. Amyloid Plaques: Abnormal processing of APP by beta and gamma- secretases produces amyloid-beta peptides. These peptides aggregate to form extracellular amyloid plaques, which disrupt cell-to-cell communication and activate immune responses, leading to inflammation and neuronal damage. 2. Neurofibrillary Tangles: Hyperphosphorylation of tau protein leads to the formation of intracellular neurofibrillary tangles. These tangles disrupt the normal function of microtubules in neurons, impairing nutrient and Pathophysiology 3. Synaptic Dysfunction and Loss: Amyloid plaques and tau tangles disrupt synaptic function, leading to a loss of synapses and neurons. This synaptic loss is correlated with cognitive decline and memory impairment. 4. Inflammation: Chronic activation of the immune system in the brain, including microglia and astrocytes, contributes to neuroinflammation. This inflammatory response exacerbates neuronal damage and disease progression. Epidemiology Prevalence: Alzheimer’s Disease is the most common cause of dementia, affecting approximately 5-10% of individuals over the age of 65. The prevalence increases with age, with nearly one-third of people aged 85 and older affected. AD is the 5th leading cause of death in adults over 65 years of age, and the 6th leading cause of death overall Demographic Factors: Age: The primary risk factor for Alzheimer’s disease is age, with the incidence increasing significantly in older populations. Genetics: The presence of the APOE ε4 allele increases the risk, especially in individuals with a family history of the disease. Gender: Women are at a higher risk of developing AD, possibly due to longer life expectancy and hormonal differences. Geographic Variations: There are some geographic differences in prevalence, potentially due to genetic, environmental, and lifestyle factors. For instance, higher rates are observed in North America and Europe Clinical manifestations  Diagnosis and treatment options Alzheimer's disease (AD) is diagnosed definitively only by autopsy, but clinical suspicion can be confirmed using biomarkers and neuroimaging like: 1. Magnetic resonance imaging (MRI). MRI uses radio waves and a strong magnetic field to produce detailed images of the brain. 2. Computerized tomography (CT). A CT scan, a specialized X-ray technology, produces cross- sectional images of your brain. It's usually used to rule out tumors, strokes and head injuries. 3. Fluorodeoxyglucose (FDG) PET. imaging scans show areas of the brain in which nutrients are poorly metabolized. Diagnosis and treatment options Treatment options: Pharmacological Interventions: e.g: Cholinesterase Inhibitors to Improve neurotransmission by increasing acetylcholine levels Non-Pharmacological Interventions: Cognitive therapy, physical exercise, and lifestyle modifications to manage symptoms and improve quality of life. Emerging Therapies: Ongoing research into disease-  Oral and dental manifestations 1. Poor Oral Hygiene: - Cognitive decline can lead to neglect of personal hygiene, including oral care. - This neglect increases the risk of dental caries, periodontal disease, and halitosis. 2. Dry Mouth (Xerostomia): - Medications commonly prescribed for Alzheimer's disease, such as anticholinergics and antidepressants, can cause dry mouth. - Reduced salivary flow increases the risk of caries, oral infections, and discomfort. 3. Mouth ulcers: - Occurrence the ulcers by friction due to reduced adhesion of the prosthesis supported by the oral mucosa. 4. Gingival Hyperplasia: - Certain medications can cause gingival overgrowth, which can further Dental Management: Behavioral Challenges: Difficulty in cooperating during dental treatments due to cognitive impairment and behavioral issues. Communication Barriers: Challenges in understanding and following dental care instructions Specialized Care Needs: Requirement for tailored dental care approaches, including sedation or general anesthesia for certain procedures Preventive Care Importance: Emphasis on regular dental check-ups, professional cleaning, and caregiver education to maintain oral health and prevent complications. References Thompson & Thompson Genetics and Genomics in Medicine Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., … & Tsuda, T. (1995). Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature, 375(6534), 754-760 Bomasang-Layno E, Bronsther R. Diagnosis and Treatment of Alzheimer’s Jankovic J, et al., eds. Alzheimer disease and other dementias. In: Bradley and Daroff's Neurology in Clinical Practice. 8th ed.