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A comprehensive overview of alzheimer's disease (ad), covering its early signs, stages, diagnosis, and treatment options. It delves into the neuroanatomical and neural network changes associated with ad, highlighting the role of acetylcholine and the mechanisms of action of various medications used in its management. The document also includes exercises and questions that can be used for study purposes.
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Early (1-3 years) signs of AD - short term memory deficits disoriented to date diminished recall of recent events mild language and decision-making deficits mild problem copying figures (clock drawing) social withdrawal mood change personality changes problems with managing finances Middle (2-8 years) stage of AD - disoriented to date and place may get lost in familiar places impaired learning new skills agitation, aggression, restlessness, or anxiety difficulty with ADLs such as cooking and grooming Late (6-12 years) stage of AD - disoriented to person, time, or place non-verbal long term memory diminished unable to groom or dress progress to need for total care at end stage incontinent motor or verbal agitation Alzheimer's disease (AD) demographic - most prevalent in people over age 65 African American (13.8%), Hispanics (12.2%), non-Hispanic whites (10.3%), American Indian and Alaska Natives (9.1%), Asian and Pacific Islanders (8.4%) Genetics r/t AD - Genes appear to play a strong role, with late-onset AD showing heritability of 58-79% and early-onset AD showing over 90% Neuroanatomy r/t AD - amyloid plaques and neurofibrillary tangles. atrophy of hippocampus and cerebral cortex. Neural Networks r/t AD - damage to synapses, mitochondrial abnormalities, and inflammatory processes Neural Signaling r/t AD - decreased acetylcholinesterase activity and a permanent loss of cholinergic neurons Acetylcholine (ACh) is a neurotransmitter necessary for processing memory and learning. Diagnosis of AD - comprehensive health history is key to gather clues Rule out other causes of dementia
Early AD may include anxiety, irritability, and sleep disruption new-onset mental health symptoms in late 50s and 60s may be in the early stage of AD Cholinesterase Inhibitors (ChEIs)X - do not change the progression of AD provide some alleviation of symptoms eg. donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne, Razadyne ER), donepezil (Aricept) Mechanism of Action - inhibits centrally active acetylcholinesterase donepezil (Aricept) Common Side Effects - gastrointestinal symptoms (nausea and diarrhea) headache dizziness muscle weakness donepezil (Aricept) Precaution - sick sinus syndrome seizure disorder donepezil (Aricept) Prescribing Pearls - Taper to avoid withdrawal effects. Donepezil (Aricept) is approved to treat moderate to severe AD at 23 mg/day dose, but there is minimal improvement in cognitive functioning when compared to a 10 mg/day dose. At the higher dose, donepezil has a higher incidence of adverse effects. When Donepezil (Aricept) is added to CYP2D6 or CYP3A4, there is a possibility of peripheral side effects, and inducers of CYP2D6 and CYP3A4 may increase the rate of elimination rivastigmine (Exelon) Mechanism of Action - acts centrally for both acetylcholinesterase and butyrylcholinesterase, thereby potentially increasing its efficacy. rivastigmine (Exelon) Common Side Effects - Common Side Effects gastrointestinal symptoms (anorexia, nausea, vomiting, or diarrhea) weakness dizziness tremor rivastigmine (Exelon) Precautions - Precautions asthma or COPD sick sinus syndrome GI Bleeding weight < 50 kg
processing. Blocking NMDA receptors protects neurons from the effects of too much glutamate without affecting normal neurotransmission Common Side Effects Memantine (Namenda) - Common Side Effects gastrointestinal symptoms (constipation, diarrhea, and weight gain) urinary frequency confusion dizziness headache cough Precautions Memantine (Namenda) - Precautions concurrent use with (amantadine, rimantadine, ketamine, or dextromethorphan) severe hepatic impairment severe renal impairment medications or conditions that increase the pH of the urine Prescribing Pearls Memantine (Namenda) - Prescribing Pearls This is used as monotherapy or in conjunction with ChEIs; when given with ChEIs, fall precautions are required and driving is forbidden due to delayed reactions. Minimal inhibition of CYP450 enzymes CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 occurs, which means there are no pharmacokinetic interactions with medications metabolized by these enzymes N-methyl-D-aspartate (NMDA) Receptor Antagonist Prescribing Pearls - Prescribing Pearls Memantine is associated with an increased life expectancy when compared to donepezil (Procyshyn et al., 2018). If treatment failure occurs, 50% of individuals respond to a different agent (Procyshyn et al., 2018). Educate clients and families that medications cannot halt or reverse the progression of Alzheimer's disease. Consider goals of care in the selection of medication. Is the management of a specific symptom or behavior the goal? Is the associated risk of the medication worth the potential benefit? These goals will inform the selection of an agent. Donepezil at a higher dose has a higher incidence of adverse effects without increased cognitive benefit. Rivastigmine (Exelon) is available in oral form or transdermal patch. The transdermal patch is used for dementia associated with Parkinson's disease. Medications that induce or inhibit CYP450 metabolism will not modify rivastigmine metabolism (Chisholm-Burns et al., 2019).Antipsychotics are not recommended for the treatment of dementia-related to agitation and behavioral symptoms (Stahl, 2021). Lifespan Considerations in treating AD - Cholinesterase inhibitors are not recommended in pregnancy and lactation.
The first-line pharmacologic treatment of aggression and agitation in dementia - SSRI/SNRI therapy Cleo is a 65-year-old male diagnosed with mild cognitive changes related to Alzheimer's disease. He also has anxiety, COPD, and smokes cigarettes. Which of the following medications is appropriate for Cleo? - donepezil A patient diagnosed with Alzheimer's disease has decided to stop treatment. The NP has educated the client that medication discontinuation will result in the return of cognitive symptoms and the medication may not work as well if restarted. The client would still like to stop the medication due to the gastrointestinal side effects. Which of the following medications requires tapering? - donepezil Rationale: Donepezil requires tapering. Rivastigmine and Galantamine do not require tapering.