Alzheimer’s Disease: Overview and Treatment Options

Jillian Blair Thomas, Pharm.D. Candidate 2013 Michael W. Frye, Pharm.D. Candidate 2013 Bernie R. Olin, Pharm.D., Associate Clinical Professor and Director Drug Information Center Auburn University, Harrison School of Pharmacy Universal Activity #: 0178-0000-12-114-H04-P | 1.5 credit hours (.15 CEUs) | Expires Dec. 12, 2015

Alabama Pharmacy Association | 334.271.4222 | www.aparx.org | [email protected] Introduction toxicity. The rate of progression of may be slowed by controlling hypertension. Diabetes Alzheimer’s disease (AD) is the most may increase the risk of dementia through common cause of dementia in the United States multiple mechanisms. Glucose metabolites may affecting an estimated 5.4 million people, with have a toxic effect on the brain, specifically over 60% of those diagnosed being women. structures of the hippocampus, and vasculature. Worldwide, an estimated 24.3 million, possibly itself may increase the risk of AD due to as many as 35 million, people have been disturbances in insulin signaling pathways 1-6 diagnosed with Alzheimer’s disease. It is peripherally and in the brain.2,5 Insulin may also estimated that by the year 2050 between 13 and have a role in the regulation of metabolism of Aβ 2, 3 16 million Americans will be affected by AD. and tau protein.2 Alzheimer’s disease is more prevalent in African Dominantly inherited forms of AD 1 Americans and Hispanics than in whites. The account for only a small percentage of cases; majority of patients with AD are 65 years or however, there is a definite genetic link.1,2,5 older at the time of diagnosis, but about 5% of There is a high familial occurrence of AD linked patients diagnosed with AD are under the age of to autosomal dominant traits on chromosomes 65. Patients who are diagnosed with AD between 21, 14, and 1.1,2,6 Mutations on these age 40 and 64 are considered to have early-onset chromosomes are associated with early-onset 2 AD. The incidence of AD increases exponentially AD.2,4,5,6 Chromosome 21 contains a gene that 1,2,5 with age. About 1 in 8 Americans age 65 and encodes for amyloid precursor protein (APP). older are affected by AD and nearly half of APP is a protein that is normally found 1-3,7 Americans over age 85. AD reduces life throughout the body. Overproduction and/or expectancy with average survival after diagnosis transcription errors can lead to the production of 1,2 being about 4 to 6 years. an abnormal subunit of APP known as beta- amyloid (Aβ).1,2 Aβ consist of Risk Factors and Genetics 36-43 amino acids. Aβ consisting of 42 amino The primary risk factor associated with acids is more neurotoxic that other amyloid AD is advancing age. Once a person turns 65 forms and is prone to aggregate and form 1,2,4,5 years old, his/her risk for AD doubles every five plaques. In fact, much of the neuronal years.6,7 Other risk factors include head trauma, damage associated with AD is caused by Aβ. metabolic syndrome, diabetes, hypertension, Chromosomes 1 and 14 are home to genes that and family history.1,2,4,5 There is growing code for proteins involved in APP processing. evidence that supports a link between Defects in these genes are associated with the 1,2,4 cardiovascular disease and its risk factors and majority of cases of early-onset AD. Even the incidence of AD.2,8 Risk factors of though there is a definite link between certain cardiovascular disease that are also risk factors genes and AD, the majority of cases of AD are 1,2 for AD are hypertension, high levels of low- considered to be sporadic. density lipoprotein cholesterol (LDL), low levels Sporadic forms of AD may be linked to a of high-density lipoprotein cholesterol (HDL), susceptibility gene, APOE. APOE is found on obesity, atherosclerosis, and diabetes.2,4,5 chromosome 19 and encodes for apolipoprotein 1,2,4,5 Dysfunctional blood vessels in the brain may E (ApoE). ApoE is normally involved in 1 impair nutrient delivery to neurons and may cholesterol and phospholipid metabolism. ApoE reduce beta-amyloid (Aβ) clearance (see is synthesized in the liver, cerebrospinal fluid, discussion below). Elevated levels of cholesterol and central nervous system and acts as a 2,4 in the brain may alter neuronal membrane transporter in the brain. ApoE is associated functioning and contribute to neuritic plaque with increased Aβ deposition and it may also formation. Vascular disease may accelerate the accelerate the progression of ; deposition of Aβ in the walls of cerebral it can bind neurofibrillary tangles (NFTs) as 2,5,6,8 vasculature, which may contribute to neuronal well. ApoE may also affect the rate of Aβ 1 Alzheimer’s Disease: Overview & Treatment Options | Alabama Pharmacy Association | www.aparx.org

clearance.4,5 The APOE gene occurs in three neurodegeneration associated with Aβ isoforms: *2, *3, and *4.1,2,5 APOE*4 is deposition.1,2,5 Neuritic plaques also contain associated with an increased risk of late-onset ApoE. Neuritic plaques may be found in patients AD.1,2,4-6,8-10 A person may have zero, one, or two without dementia, but plaques found in these APOE alleles; the more APOE*4 alleles present, patients do not contain abnormal proteins.1 The the greater the risk of developing AD.1,2,4-6,8,9 amount of amyloid deposition in neuritic plaques is related to the severity of neuronal damage; Pathophysiology however, Aβ does not correlate with disease severity as strongly as does NFT density.1,8,9 The most obvious findings in a brain Neurotransmitters and enzymes are also affected by AD are atrophy and synapse loss; affected by AD. Acetylcholine (ACh) is one of the however, these features alone are not diagnostic main neurotransmitters affected by AD.1,2 because a certain amount of atrophy and Choline acetyltransferase levels are reduced by synapse loss may occur with normal aging. up to 90% in the cortical and hippocampal Atrophy due to AD is mainly found in the regions.1 The extent of reduction in choline temporal, parietal, and frontal lobes of the brain acetyltransferase concentration is related to and synapse loss is most pronounced in the plaque density and disease severity.1,2,5 ACh and hippocampus.1,2,5 The main changes seen in the acetylcholinesterase concentrations are reduced cerebral cortex of patients with AD are NFTs and in patients with AD. Muscarinic receptors in the neuritic plaques.1,2,4,8 cortex and hippocampus usually remain at NFTs are most likely to form in large normal or near-normal levels until late-disease. pyramidal neurons and, as such, are found AD leads to a reduction in the number of primarily in the pyramidal regions of the nicotinic receptors in the brain. Cholinergic neocortex, hippocampus, and amygdala.1,5 NFTs activity is most significantly altered by AD, but may also be found in the brainstem and locus norepinephrine, serotonin, glutamate, and ceruleus. Typically, NFT formation begins in the gamma-aminobutyric acid activity are also hippocampus and spreads to the neocortex.1,2,6,8 affected.1,2,5 NFTs are composed of paired helical filaments It has been proposed that oxidative containing abnormally phosphorylated tau stress, mitochondrial dysfunction, and protein.1,2,4,6,8 Tau protein normally provides postmenopausal loss of estrogen may have a structural support for microtubules in the cell, role in the pathogenesis of AD. Oxidative stress but cannot bind properly due to abnormal and free-radical build-up may contribute to the phosphorylation.2,3,5 The inability of tau protein development and progression of AD.1,2,5 to function normally results in cell death due to Mitochondrial dysfunction disrupts neuronal an abnormally functioning microtubule system.2,5 energy metabolism and contributes to free Severity of dementia is associated with the radical accumulation, oxidative stress, and density of NFTs which are a sign of neuronal ultimately apoptosis.2,5 Estrogen is involved in death.2,5,8,9 neuronal growth and maintenance of normal Neuritic plaques are spherical bodies of cholinergic activity; it may also have antioxidant tissue composed of granular deposits and the properties. Loss of estrogen due to menopause remnants of neuronal processes. Neuritic results in loss of the normal activities of estrogen plaques have a three-tiered structure consisting in the brain.2 All three of these mechanisms may of a central amyloid core, a middle region of contribute to the pathogenesis of AD. swollen axons and dendrites, and an outer zone 1,6,8 of degenerating neuritic processes. The Diagnosis and Staging amyloid core contains APP which can be cleaved to form neurotoxic Aβ.1,2 Neuritic plaques Currently, a definitive diagnosis can only contain acute-phase inflammatory mediators be made post-mortem, but advances in due to local inflammation and diagnostic technology have made clinical

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diagnosis of AD up to 90% accurate when Table 1: Factors that may cause symptoms of compared to post-mortem diagnosis.1,4 When cognitive impairment making a clinical diagnosis, it is important to rule Diseases that may that may out other, potentially reversible, causes of affect cognitive affect cognitive function impaired cognition. There are numerous function medications and diseases that can negatively • Adjustment • Anticholinergic affect cognition (see Table 1).1,2,4,8,9 A thorough disorder agents patient history is important because it • Amnestic • Anticonvulsants syndrome • Antidepressants documents symptoms and progression and it • Delirium • Antihistamines may indicate or help rule out potential causes of • Depression • Antineoplastic agents 2,4,9 cognitive impairment. Neuropsychological • Brain abscesses • Antipsychotics testing may be performed, including a • Normal pressure • Anti-arrhythmics depression screening and in-depth assessment of hydrocephalus • Anti-hypertensives • the patient’s cognitive function.1,2,6,8 • Corticosteroids • Subdural • H-2 receptor Neuropsychological testing should be performed hematoma antagonists by a clinician that is trained to administer and • Tumor within the • Immunosuppressants 1,6 interpret the results of the tests. Tests such as central nervous • Narcotic analgesics a mini- mental status examination, Blessed system • NSAIDs • Dementia scale, Clinical Dementia Rating scale, Cardiac • Sedative hypnotics arrhythmia • Short Test of Mental Status, or other tests that Anxiolytics • Heart failure • Skeletal muscle assess cognitive function may also be • Vascular relaxants performed.1,2,6,8 Tests that assess functional occlusion capacity, such as the Functional Activities • Vitamin B-12, Questionnaire, may also be beneficial.9 Brain folate, or iron deficiency scans are useful in determining the potential • Infections cause of impaired cognition and the extent of AD • Metabolic neuropathology. Magnetic Resonance Imaging disorders (MRI) and computed tomography (CT) scans are Adapted from Table 103-3. In: Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR. Koda-Kimble the most commonly used methods for and Young’s applied therapeutics: the clinical use of drugs. 10th ed. performing brain scans; however, there are Philadelphia: Wolters-Kluwer Health; c2013. p.2377. other types of scans that may be used in addition to or instead of an MRI or CT scan.1,2,4,8 Certain Before treating AD, it is important to biomarkers, such as Aβ and tau levels in determine what stage of disease the patient is cerebrospinal fluid, may also be measured to experiencing. There are two main scales used to help diagnose a patient with AD.3,9,10 The goal of determine the patient’s current state and their all these tests is to determine whether or not the prognosis, the Global Deterioration Scale and the patient meets the Diagnostic and Statistical Clinical Dementia Rating Scale. Based on these Manual of Mental Disorders fourth edition rating scales, the patient’s stage can be (DSM-IV) criteria for dementia. Once a diagnosis determined and described, as can the patient’s of dementia is determined to be probable, the prognosis based upon the current state of their patient may be classified as having dementia of dementia. The description of each stage of AD is based upon the patient’s current level of the Alzheimer’s type based on whether or not 1,2 he/she meets criteria established by the National cognitive function and is defined in Table 2. Institute of Neurological Disorders and Stroke, Alzheimer’s Disease and Related Disorders Association, American Academy of Neurology, or other reputable institution.1,2

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Table 2: Stages of Cognitive Decline Adapted from Table 103-6. In: Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR. Koda-Kimble Stage of Cognitive Features/Description and Young’s applied therapeutics: the clinical use of drugs. 10th ed. Decline Philadelphia: Wolters Kluwer Health; c2013. p.2377. None Cognitive state remains Goals of Therapy normal; no change from normal Once the stage of the patient’s disease Very mild Often forgetful; no has been determined, a treatment plan can be clinical/objective decline formulated. The main initial goal of therapy for noted AD is to maintain the patient’s independence for Mild Worsening of patient’s as long as is possible. This is considered best for condition is noted upon both the patient and the patient’s caregiver. For psychiatric testing; ability the patient, maintaining independence allows to maintain a job and him/her to remain within familiar surroundings, social function are as opposed to moving them to a facility or affected; patient may alternative site for care with surroundings that experience anxiety or are unfamiliar to the patient and, consequently, denial about condition, but to which he/she must adapt. Once this goal of in a mild form therapy has been addressed, focus can then be Moderate Affect appears flat and placed on the therapeutic goals of treatment.1 patient may seem The goals of therapy are as follows: treat withdrawn; concentration symptoms and cognitive impairment; preserve ability and ability to the patient’s current level of cognition; perform complex tasks are effectively manage and treat psychiatric and diminishing behavioral complications; and provide Moderate/Severe Dementia begins to appropriate education to the patient and their develop (early stages of family/caregiver with particular focus placed on the disease); interactions overall expectations for the time course of the with others become illness, expectations for each therapy option troublesome for the employed (both pharmacologic and non- patient; orientation to pharmacologic), and financial expectations of people or place begins to therapy.2 be diminished Severe Assistance performing Treatment normal daily activities (i.e. bathing, dressing, etc.) is Treatment for AD is based upon well- needed; behavioral established drug classes, investigational agents, symptoms begin to and non-pharmacological recommendations. manifest (i.e. agitation, Pharmacological treatment is based around two delusions, aggressive primary classes of pharmacological agents, the cholinesterase inhibitors and the n-methyl-d- behavior) aspartate (NMDA) receptor inhibitors. Very Severe Thinking and motor skills Investigational agents include estrogen, anti- are lost; ability to speak inflammatory agents, monoamine oxidase and communicate inhibitors (MAO-Is), herbal medications and effectively is lost; urinary vitamins, and cholesterol lowering medications. incontinence may develop; It should be noted that these patients often patient’s become totally experience non-cognitive symptoms, including dependent upon psychosis, inappropriate/aggressive behavior, caretakers and depression. For these symptoms,

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Alzheimer’s patients often receive antipsychotic no longer commonly used.1,2,11-13 medications, antidepressants, and/or (Aricept®), similar to , is anticonvulsant medications. Non-pharmacologic indicated for the treatment of mild to moderate recommendation range from proper patient and AD. However, unlike tacrine, it is also approved family education to avoiding of environmental for the treatment of moderate to severe forms triggers of symptoms.1,2 of the disease. 1,2,6,11-13 It is more selective for its The mainstay of treatment for AD is the reversible inhibition of AchE than for BchE, and it drug class of cholinesterase inhibitors.1,2 The also tends to be more specific for inhibition of cholinesterase inhibitors that are available for the cholinesterases of the CNS and less for the treatment of Alzheimer’s are donepezil peripheral cholinesterases.1 Donepezil is given (Aricept®), (Exelon®), once daily in a dose of 5-10 mg, due to its high (Razadyne®), and tacrine (Cognex®). These bioavailability and somewhat extended half-life. medications are designed to increase cognitive The adverse effect profile of this is functioning via enhancement of cholinergic mainly due to its effects on the cholinergic activity. They accomplish this by increasing the system within the body, and includes nausea, availability of acetylcholine within the central headache (HA), syncope, loss of appetite, nervous system (CNS) through inhibition of the insomnia, and vivid dreams, just to name a few. breakdown of acetylcholine by various Serious adverse effects with the use of donepezil cholinesterases, both acetylcholinesterase are rare, but include gastrointestinal (GI) (AchE) and butyrylcholinesterase (BchE).1,2,11-13 hemorrhage, atrioventricular (AV) blockade, and Tacrine was the first medication within Torsades de pointes.1,6,11-13 Donepezil is this class developed for the treatment of AD.2 It recommended to be given at bedtime to allow is labeled for the treatment of mild to moderate the patient to better tolerate the cholinergic states of Alzheimer’s dementia and gained adverse reactions. It is metabolized by CYP 3A4 approval in 1993.11-13 Tacrine inhibits both AchE isoenzymes and overall, it is well tolerated by and BchE within both the CNS and the periphery most patients. Donepezil has been shown to of the body in a reversible fashion.1,11-13 It is produce improvements in cognitive function recommended to initially give as 10 mg doses within 12-24 weeks of initiation of therapy, even four (4) times daily due to its low in the case of adverse effects or a suspected loss bioavailability.11 Tacrine, however, is limited by of efficacy.1,14 These improvements can be seen its adverse reaction profile, namely for as long as two years in some cases. As hepatotoxicity, which has rendered the use of mentioned previously donepezil is approved for the medication as a last option.1,2 The less the treatment of moderate to severe forms of severe adverse reactions possible with the use of AD, and, thus, is the only medication indicated this medication are primarily gastrointestinal for this stage of the disease.1 related and include nausea, vomiting, and Rivastigmine (Exelon®) is another diarrhea (NVD); indigestion; loss of appetite; and cholinesterase inhibitor that reversibly inhibits myalgia. The more severe adverse reactions cholinesterase enzymes.1,2,6,11-13,15 It differs from possible include elevations of liver tacrine in that it produces its cholinesterase aminotransaminase levels, hepatotoxicity, liver inhibition primarily within the CNS, similar to failure, bradycardia, heart block, and a lowering donepezil. It is different from donepezil in that it of the seizure threshold. It is broken down inhibits both AchE and BchE, whereas donepezil mainly by cytochrome (CYP) enzymes within the is more selective for AchE.1 It is approved for the liver.1,11-13 Tacrine has been shown to lead to low treatment of mild to moderate stage AD, but not levels of improvement in cognitive function with for the moderate to severe stage of the at least 12-24 weeks of therapy; however, as disease.1,2,6,11-13 Rivastigmine is also different mentioned previously, due to the adverse effects from all of the other cholinesterase inhibitors in caused by tacrine and the availability of newer that it comes in both oral dosage forms and a agents with less severe adverse effects, tacrine is topical dosage form (extended release patch). It

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is dosed initially at 1.5 mg given twice daily to be maximum dose of 24 mg daily. Improvements in titrated by 1.5 mg/dose (3 mg/day) cognitive function have been seen with use of approximately every two weeks, not to exceed a this medication. 1,16 maximum of 6 mg/dose (12 mg/day). Initial (Namenda®) is the only dosing for the patch is 4.6 mg (patch)/day to be other medication, aside from donepezil, increased to the 9.5 mg (patch)/day indicated for the treatment of moderate to maintenance dose no earlier than four weeks severe AD; however, it does not fall into the class after initiation. The maximum recommended of the cholinesterase inhibitors. It antagonizes daily dose for this dosage form is 9.5 N-methyl-D-aspartate glutamate receptors. mg/day.1,6,11-13,15 Similar to donepezil, the Glutamate within the CNS can cause adverse effect profile of rivastigmine is much excitotoxicity leading potentially to cell death. milder than that of tacrine. Mild adverse effects Since it has a different mechanism of action, it is that may be seen include HA, dizziness, fatigue, commonly employed in a combination with a and gastrointestinal effects (NVD, loss of cholinesterase inhibitor. However, monotherapy appetite). Rivastigmine is the only with this agent may be just as effective as the cholinesterase inhibitor used for the treatment combination with donepezil.17 It should be noted of AD which is not metabolized by CYP that this medication should not be used as enzymes.1,2,6,11-13,15 It is metabolized by monotherapy in a patient suffering from only hydrolysis. As the adverse effects are most mild to moderate forms of the disease.6 commonly seen when rivastigmine is taken on an Generally, memantine is tolerated well by most empty stomach or when the rivastigmine dose is patients. 1 Due to having no effect on the increased too rapidly, it is recommended that cholinergic system, the adverse effect profile of this medication be given with food.1 memantine is milder than the cholinesterase Galantamine (Razadyne®) is the final inhibitors. The common adverse effects cholinesterase inhibitor used for the treatment associated with the use of this medication of AD. It is indicated for the treatment of mild to include dizziness, constipation, and headache. moderate forms of AD. Similar to galantamine The severe adverse effects that are possible with and tacrine, it is not indicated for the treatment the use of memantine include cardiac failure, of moderate to severe forms of the transient ischemic attack, deep vein thrombosis, disease.1,2,6,11-13 It has a slightly different seizure, liver failure, or acute renal failure. While mechanism than that of the other cholinesterase most of these effects are very rare, the inhibitors. In addition to reversibly inhibiting cardiovascular effects occur with the greatest AchE mostly within the CNS, it also acts to frequency (about 1%).13 Memantine is initiated activate nicotinic type receptors at a site at 5 mg daily and titrated according to the different to that of which is stimulated by its following schedule: 5 mg daily initially for one cholinesterase activity. Hence, the stimulation week, then 15 mg daily divided into two doses, of these nicotinic receptors does not require the then 10 mg two times daily.1,6,11-13 Memantine presence of Ach or Bch.1,6,11-13 As was the case has been shown to improve cognitive function, with donepezil and rivastigmine, galantamine as well as reduce the overall responsibility of the has a mild adverse effect profile. The mild patient’s caregiver.1 adverse effects associated with the use of galantamine are mainly associated with the Alternative Therapies cholinergic system including HA, bradycardia, There are various medications currently and gastrointestinal effects (N/V/D). under investigation for the treatment of AD. Galantamine is metabolized by multiple CYP Estrogen has been shown to increase blood flow isoenzymes. Galantamine is dosed two times within the cerebrum of the brain, allowing for daily, initially at a 4 mg dose. 1,2,6,11-13 It is better delivery of glucose and increase repair of recommended that the dose of galantamine be damaged neurons. These may provide beneficial titrated no sooner than every 4 to 6 weeks,

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effects for patients with AD. The benefits were patient’s memory. Ginkgo biloba may exhibit first noticed in women taking hormone antioxidant properties, and may also enhance replacement therapy. A lower incidence of AD cholinergic function in Alzheimer’s patients. was noted in these women and lead to current While improvements in cognitive function investigation into their use for AD.1,2 appear promising, there is not enough evidence Monoamine oxidase inhibitors (MAO-Is) to fully support the use of ginkgo biloba for are another drug class under investigation for improvement in the patient’s Alzheimer’s the treatment of AD as a result of the finding of condition .1,2 high levels of MAO type B in patients with AD. Other agents currently under Use of the MAO-B inhibitor, , has been investigation for the treatment of AD include the shown to increase cognitive functioning in some 3-hydroxy-3-methyl-glutaryl coenzyme (HMG trials. 1 This, coupled with the fact that these CoA) reductase inhibitors, also known as the agents can be used in the treatment of statins; anti- monoclonal antibody depression, has led to a promising investigation agents; alpha and beta secretase inhibitors (i.e. into the use of these medications for treatment rosiglitazone, semagacestat); valproate for a of AD.1,2,11-13,18,19 reduction of tau phosphorylation; and omega-3- Cerebrolysin is a medication approved fatty acids, to name a few.20 This is an active for the treatment of AD in various other area of clinical investigation. countries, but not in the U.S. Made from The final drug therapy options available purified human brain proteins and purified for for the treatment of AD focus more on the use in humans, cerebrolysin can freely cross the impact of AD on the patient’s daily life and blood brain barrier to exhibit its beneficial common comorbid conditions. Many AD effects in Alzheimer’s patients, which include patients experience significant depression or protective and supportive effects on neuronal anxiety. There are many drug classes involved function. This is thought to enhance cognitive with the specific treatment of each of these function in these patients. Cerebrolysin may also conditions.1,2 have anti-inflammatory effects, may interact Depression associated with AD is treated with GABA receptors, may interact with amlyoid in a similar manner to clinical depression. The proteins, and may enhance the actions of some medication classes employed for the treatment neuroprotective peptides. None of these of this type of depression include the selective mechanisms have been proven, nor are they well serotonin reuptake inhibitors (SSRIs) (i.e. understood.20 sertraline, fluoxetine), the serotonin- Non-steroidal anti-inflammatory drugs norepinephrine reuptake inhibitors (SNRIs) (i.e. (NSAIDs) have also come under investigation for venlafaxine, duloxetine), the norepinephrine use as a potential treatment of AD. It is thought reuptake inhibitors (i.e. bupropion), the tricyclic that inhibiting inflammation in the CNS could antidepressants (TCAs) (i.e. , possibly lead to reduced formation of neuritic desipramine), the tetracyclic drugs (i.e. plaques, leaving the patient potentially with a mirtazepine), and the monoamine oxidase better cognitive state. Clinical trials have only inhibitors (i.e. selegiline). For a more extensive been able to establish a decreased risk of discussion of the treatment of depression, refer inflammation with use of these medications in to pharmacotherapeutic texts and the most up- Alzheimer’s patients, but there has been no to-date guidelines.1,2,18,19 improvement of cognitive symptoms shown with Anxiety is another condition that their use.1,2 patients with AD may experience. This becomes The herbal supplement, ginkgo biloba, is more common as the patient’s cognitive function the only OTC product under investigation for declines and their lack of memory leads them to improved cognitive function in patients with AD. experience anxiety. Like depression in AD, Speculation for the use of this medication is anxiety disorders in a patient with AD is treated based upon its potential ability to enhance the much the same as in other patients. The

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medication therapy employed for the treatment many as 16 million Americans by the year 2050.1- of this type of anxiety varies depending on the 6 Currently, there are no proven strategies to diagnosis, but treatment may include prevent AD. Controlling risk factors for benzodiazepines (BDZs) (i.e. diazepam, cardiovascular disease, such as blood pressure, lorazepam), buspirone, SSRIs (i.e. sertraline, cholesterol, and weight, especially in mid-life, fluoxetine), TCAs, venlafaxine, and others. The may help reduce the risk of developing AD. reader is referred to pharmacotherapeutic texts Staying physically, mentally, and socially active and the most up to date set of guidelines may also help reduce the risk of developing AD. available.1,2,21,22 Physical activity may directly protect the brain by stimulating blood flow and oxygen delivery, and Prognosis it also helps maintain cardiovascular health. The mechanism by which mental activity and social AD follows a predictable course and may interaction may help reduce the risk for AD is progress over a period of 10 or more years. unknown, but stimulation of the brain is thought Multiple areas of cognition are affected by AD.1,2 to be beneficial.7,23 As head trauma is a risk Initially, a patient may have vague complaints factor for AD, wearing a helmet when riding a about memory impairment or family may bicycle or participating in contact sports can help consider the patient to be forgetful.2,9 Patients prevent head trauma. For older patients, may also present with mild cognitive impairment carefully going through the home and removing (MCI), a condition in which cognitive impairment possible tripping hazards can help prevent falls is present and greater than expected for the and related head trauma. Minimizing head patient’s age but not significant enough to trauma will not lower a patient’s risk for diagnose dementia.2,6,9 MCI may be the initial developing AD, but it can help keep a patient’s manifestations of AD, but not all patients with risk as low as possible.23 At the present time, MCI progress to AD.2,8 Rating scales may help to there is no way to prevent AD; however, the gauge patient deterioration. The global above strategies may be beneficial in reducing deterioration scale and clinical dementia rating risk.7,23 scale are both appropriate tests for measuring 2 deterioration of a patient’s disease. Patients Conclusion should have cognitive function reassessed on a scheduled basis, possibly every 6 months, so that AD causes degeneration of neurons in disease progression can be documented and higher brain areas.1,2 The most significant therapy can be monitored closely to ensure consequence of AD is the loss of cortical and appropriateness.2,6,9 As AD progresses, hippocampal neurons as synapse loss is behavioral symptoms may appear and should be associated with disease severity.1,5,10 NFTs and treated accordingly.2,6 Towards the later stages cell loss are centralized in the cerebral cortex of AD, loss of daily function may occur and the and hippocampus.1,5,10 AD is also responsible for patient will eventually get to a point where vast destruction of cholinergic pathways.1,2,5 The home care is not appropriate; a residential pathologic processes of AD may begin many facility may be necessary in order for the patient years before symptoms are seen.1,2,6,8,10 to receive adequate care. Infections, specifically Treatments such as the cholinesterase inhibitors pneumonia, are the most common cause of and memantine may provide some relief from death in patients with late-stage AD.1,2 symptoms, but there is no cure for AD. Even with treatment, patients with AD will experience Risk Reduction cognitive impairment that progressively worsens until death.1,2 Over 5 million American are suffering from AD, and it is predicted that AD will affect as

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References:

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9 Alzheimer’s Disease: Overview & Treatment Options | Alabama Pharmacy Association | www.aparx.org