Alzheimer's Disease: A Disease of Deterioration

In the struggle with Alzheimer’s disease, pharmacists can provide pertinent information about the associated myths, realities, and symptomatic treatments.

For most Americans, the words “Alzheimer’s disease” (AD)— often mispronounced purposefully or by accident as “old timers’ disease”—mean devastating end-of-life memory loss and stigma.¹ The information about AD—often learned solely through the media—may lead individuals to believe that AD is inevitable (it isn’t),^2,3 and they may think that all AD patients receive poor care (there are many remarkably good AD units).^4,5

Many individuals may see a future burdened with more dementia patients and fewer societal resources to care for them (a real possibility).⁵

In general, pharmacists are well aware of what AD is and isn’t (see “Refreshing Your Memory: What Is Alzheimer’s Disease?”). Complex and relentlessly progressive, AD affects patients, loved ones, and caregivers adversely. Pharmacists can provide pertinent information about AD’s myths, realities, and available symptomatic treatments.

Relentlessly Progressive

AD’s harbinger is language difficulties, including aphasia (language disturbance), apraxia (inability to carry out motor functions), and agnosia (failure to recognize or identify objects). Patients often create new words for items. They may call a pencil a “list writer,” or a key a “door turner.”¹⁴ Clinicians stage AD as mild, moderate, or severe on the patient’s cognitive and memory impairment, communication problems, personality changes, behavior, and loss of control of bodily functions (Figure).¹³ People often dismiss mild AD as normal cognitive decline or senility—in other words, “normal” aging. For this reason, most people don’t seek treatment and are diagnosed in the late mild to early moderate stage.

In the severe stage, difficulty swallowing elevates risk of aspiration pneumonia, which often starts the downward spiral to death.^10,15

Management

AD has no cure. A handful of pharmacologic treatments—acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists—alter the decline trajectory. These treatments slow disease progression, enhance cognitive function, delay cognitive decline, and decrease disruptive behaviors. Not all patients respond to these medications, but experts generally believe that those who do will show mild to modest improvements for 6 months to a year.^16,17 Although the drugs’ effects are short-lived, they improve patients’ quality of life and briefly allow independence.^17,18

All approved drugs are most effective at their target dose, and all require slow titration to the target dose (Online Table).^19-21

(Scroll down to continue reading.)

Table: Medications Approved for Treating Alzheimer’s Disease

Drug

Approved Indication

Patient Information

Common Adverse Effects

Cholinesterase Inhibitors

Donepezil (Aricept and various generics)

All stages

• Take in the evening without regard to food, with a full glass of water

• Do not break or crush immediate-release tablet

• Orally disintegrating tablet: allow tablet to dissolve in mouth followed by a glass of water

• Available as an ER form for once- daily dosing

• Appetite loss

• Dizziness

• Fatigue

• Increased frequency of bowel movements and diarrhea

• Insomnia

• Muscle cramps

• Nausea, vomiting

• Weight loss

Galantamine (Razadyne, Razadyne ER and various generics)

Mild to moderate

• Take the ER capsule in the morning with food and water

• Take other tablet formulations and oral solution twice a day with morning and evening meal

• Liquid form can be mixed in 4 oz of juice if needed

• Maintain adequate hydration

Rivastigmine (Exelon and various generics)

All stages

• Take oral formulation with food; liquid form may be mixed in small glass of water or cold fruit juice

• Consider the patch for patients who have difficulty eating or swallowing or who have severe nausea

• Apply topical patch to clean, dry intact skin on upper or lower back once a day, alternating on the upper arm or chest

N-methyl-D-aspartate Receptor Antagonist

Memantine (Namenda)

Moderate to severe

• Take at the same time daily without regard to food

• Available as immediate release, ER, or liquid

• Administer the liquid form using the calibrated dosing device

• Prescribed alone or in combination with donepezil

• Renally eliminated drug; dose adjustments needed for creatinine clearance <30

• Educate patients about significant reactions (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin; seizures; swelling of face, lips, tongue, or throat)

• Confusion

• Constipation

• Diarrhea

• Dizziness

• Headache

ER = extended release.

Adapted from references 19-21 and the following: Aricept [prescribing information]. Eisai Inc and Pfizer Inc; 2014. www.aricept.com. Accessed January 16, 2014. Razadyne [prescribing information]. Janssen Pharmaceuticals; 2014. www.razadyneer.com. Accessed January 16, 2014. Exelon [prescribing information]. Novartis; 2014. www.exelonpatch.com. Accessed January 16, 2014. Namenda [prescribing information]. Forest Laboratories, Inc; 2014. www.namendaxr.com. Accessed January 16, 2014.

Determining when medications stop providing a therapeutic benefit and should be discontinued is challenging. Clinicians use various methods to monitor decline, including mental status tools, patient self-report, and loved ones’ observations. Most clinicians continue the drugs if the patient seems to tolerate the medication well and can afford it, and if there seems to be a benefit.¹⁶

With disease progression, specific behavioral symptoms including depression, agitation, hallucinations, and sleep disturbances become concerns. Antianxiety drugs, antipsychotics, and antidepressants are sometimes used to alleviate symptoms, but behavioral strategies are much preferred if they work.²²

Final Thought

The FDA hasn’t approved a new drug for AD since 2003.¹⁶ Experts are cautiously hopeful and actively pursuing treatments to stop or significantly delay its progression. Some researchers have identified a link between AD and diabetes mellitus, obesity, and cardiovascular disease, suggesting that this condition be called type 3 diabetes mellitus.^23,24 Some coumarin and flavonoid derivatives seem to offer promise.¹⁹ Two monoclonal antibodies—bapineuzumab and solanezumab&mdash;navigated phase 3 trials, but with disappointing results. Regardless, other monoclonal antibodies are in the pipeline.²⁵

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy. She has extensive experience with the geriatric population.

References:

• World Alzheimer report reveals negative perceptions about people with dementia. Alzheimer's Association. https://www.alz.org/news_and_events_negative_perceptions.asp. Accessed January 15, 2014.
• Survey shows two-thirds of Europeans, North Americans still associate dementia with “aging process.” PR NewsWire UK. http://www.prnewswire.co.uk/news-releases/survey-shows-two-thirds-of-europeans-north-americans-still-associate-dementia-with-aging-process-154357825.html. Accessed January 15, 2014.
• Alzheimer’s treatments. Bright Focus Foundation website. www.ahaf.org/alzheimers/treatment/common/. Accessed December 14, 2013.
• Alzheimer's/dementia in the United States. Savannah Morning News. http://www.pharmacytimes.com/_media/_pdf/Savannah_Morning_News_7-4-10.pdf. Accessed January 20, 2014.
• Nearly 15 million Alzheimer’s and dementia caregivers provide unpaid care valued at more than $200 billion. PR Newswire. http://www.prnewswire.com/news-releases/nearly-15-million-alzheimers-and-dementia-caregivers-provide-unpaid-care-valued-at-more-than-200-billion-117984029.html. Accessed January 15, 2014.
• What is Alzheimer’s? Alzheimer’s Association website. www.alz.org/alzheimers_disease_what_is_alzheimers.asp. Accessed December 14, 2013.
• What is Alzheimer’s disease? National Institute on Aging website. www.nia.nih.gov/Alzheimers/AlzheimersInformation/GeneralInfo/. Accessed December 14, 2013.
• Alzheimer’s facts and figures. Alzheimer’s Association website. www.alz.org/alzheimers_disease_facts_and_figures.asp#key. Accessed December 14, 2013.
• Leading causes of death in the United States. Centers for Disease Control and Prevention website. www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf. Accessed December 14, 2013.
• Anderson H. Alzheimer disease. Medscape website. http://emedicine.medscape.com/article/1134817-overview. Accessed December 14, 2013.
• Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer’s disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60:1119-1122.
• Study identifies predictors of Alzheimer’s disease longevity. National Institute on Aging website. www.nia.nih.gov/newsroom/2004/04/study-identifies-predictors-alzheimers-disease-longevity. Accessed December 14, 2013.
• Symptoms and stages of Alzheimer’s disease. Alzheimer’s Disease Research website. www.ahaf.org/alzheimers/about/symptomsandstages.html. Accessed December 14, 2013.
• Zanni GR, Wick JY. Differentiating dementias in long-term care patients. Consult Pharm. 2007;22:14-16, 18, 21-28.
• About Alzheimer’s: life expectancy. Alzheimer’s Foundation of America website. www.alzfdn.org/AboutAlzheimers/lifeexpectancy_pr.html. Accessed December 14, 2013.
• Schneider LS. Alzheimer’s disease pharmacologic treatment and treatment research. Continuum. 2013;19:339-357.
• Treatments for Alzheimer’s disease. Alzheimer’s Association website. www.alz.org/alzheimers_disease_treatments.asp. Accessed December 14, 2013.
• Medications for memory loss. Alzheimer’s Association website. www.alz.org/alzheimers_disease_standard_prescriptions.asp. Accessed December 14, 2013.
• Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer’s disease. Arch Pharm Res. 2013;36:375-399.
• Cholinesterase inhibitors. Drug Facts & Comparisons website. www.factsandcomparisons.com. Accessed December 14, 2013.
• Namenda. Drug Facts & Comparisons website. www.factsandcomparisons.com. Accessed December 14, 2013.
• Ballard C, Corbett A. Agitation and aggression in people with Alzheimer’s disease. Curr Opin Psychiatry. 2013;26:252-259.
• Vignini A, Giulietti A, Nanetti L, et al. Alzheimer’s disease and diabetes: new insights and unifying therapies. Curr Diabetes Rev. 2013;9:218-227.
• Nelson L, Tabet N, Richardson C, Gard P. Antihypertensives, angiotensin, glucose and Alzheimer’s disease. Expert Rev Neurother. 2013;13:477-482.
• Prins ND, Scheltens P. Treating Alzheimer’s disease with monoclonal antibodies: current status and outlook for the future. Alzheimers Res Ther. 2013;5:56.