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The number of Americans living with Alzheimer’s Disease (AD) is growing. According to the latest data from the Alzheimer’s Association, 6.5 million people in the US over age 65 are living with Alzheimer’s in 2022—that’s about 1 in 9 people over 65 (Alzheimer’s Association, 2022).
This number is expected to increase significantly—to a projected 12.7 million by 2050—unless researchers find effective ways to prevent and treat it.
But so far, the effort has been relatively unsuccessful. While there has been some progress in better understanding Alzheimer’s and in developing and testing new treatments, there’s currently no cure for Alzheimer’s disease or effective ways to prevent it.
The US Food and Drug Administration (FDA) has approved medications for treating Alzheimer’s disease that fall into two categories: drugs that temporarily mitigate some symptoms of Alzheimer’s disease and medicines that may change disease progression in people with Alzheimer’s.
Alzheimer’s drugs that treat symptoms
Alzheimer’s leads to the loss of brain cells and connections between brain cells, and these changes worsen over time. Alzheimer’s is a progressive disease, often beginning with mild memory loss and worsening symptoms over time (Bloom, 2014).
There are a number of prescription medicines for Alzheimer’s disease to help temporarily improve some of the symptoms that affect memory and thinking. These medications can’t stop or prevent the disease from progressing but may help improve quality of life, at least temporarily. These drugs work by affecting certain chemicals involved in carrying messages between the brain’s nerve cells.
Even though not a cure, the following drugs can help people affected by AD keep their independence for longer.
Acetylcholinesterase (AChE) inhibitors
Scientists do not yet fully understand how cholinesterase inhibitors work, but these drugs are thought to boost communication between brain cells. They do this by preventing the breakdown of acetylcholine, a substance in the brain that helps nerve cells communicate with each other. A higher concentration of acetylcholine in the brain leads to better communication between nerve cells, possibly easing some AD symptoms for a while (Birks, 2006).
As Alzheimer’s progresses, there’s less and less acetylcholine in the brain, so these medicines may lose their effect. The cholinesterase inhibitors most commonly prescribed are:
- Donepezil (brand name: Aricept): approved for all stages of Alzheimer’s (FDA, 2012)
- Rivastigmine (brand name: Exelon): approved for mild-to-moderate Alzheimer’s (FDA, 2018)
- Galantamine (brand name: Razadyne): approved for mild-to-moderate Alzheimer’s (FDA, 2016)
These are usually the first drugs a healthcare provider tries. Common side effects may include nausea, vomiting, and loss of appetite. Fortunately, side effects typically improve after a few weeks of taking the medication.
There’s no difference in how well these three different drugs work. One analysis of several clinical trials of donepezil, galantamine, or rivastigmine in over 3000 patients with mild to moderate AD found they all led to modest improvements (Birks, 2006).
This type of drug is believed to work by blocking the activity of a chemical messenger called glutamate. An excessive amount of this chemical in the brain is thought to lead to nerve cell damage. There are two main drugs in this class:
- Memantine (brand name: Namenda): Approved for moderate-to-severe Alzheimer’s and often prescribed for those who cannot take or don’t tolerate AChE inhibitors (FDA, 2013)
- Donepezil and memantine (brand name: Namzaric): This drug combines a cholinesterase inhibitor and a glutamate regulator. It’s approved for moderate-to-severe Alzheimer’s disease (FDA, 2014)
Alzheimer’s drugs that may change disease progression
Drugs that target the cause of disease do more than treat its symptoms. These so-called “disease-modifying drugs,” in the case of AD, are intended to modify the steps leading to the disease and treat it at its core.
Currently, only one disease-modifying drug is approved to treat Alzheimer’s. This medication, called aducanumab, targets amyloid plaques—the kind of protein deposits thought to lead to changes in the brains of people with AD (FDA, 2021).
In 2021, the FDA granted accelerated approval for aducanumab. In clinical trials, this drug reduced amyloid deposits in the brains of people with mild AD. And while that sounds promising, there’s some uncertainty about whether the drug actually slows down the progression of cognitive decline. For now, the drug is approved for people with mild cognitive impairment or mild Alzheimer’s disease.
That means before a specialist prescribes this medication, an experienced clinician will perform certain tests to evaluate whether amyloid plaques are present in the brain, and what stage of Alzheimer’s is present (FDA, 2021). Future studies will give us a better idea about this new drug’s benefits.
Non-drug treatments for Alzheimer’s disease
Drugs to manage the symptoms of Alzheimer’s disease are only one aspect of treatment. There are many strategies that don’t involve medications that can help people with the condition, particularly in the earlier stages of Alzheimer’s.
One of the advantages of non-drug treatments is not having any of the side effects that can complicate drug treatment. The umbrella term for non-drug treatments for AD is “cognitive rehabilitation,” which can include a number of different strategies. The goal of cognitive rehabilitation is to help people learn strategies to make up for declining brain function in the early stages of AD—basically, using the parts of the brain that are working to help the parts that are not.
Here are some examples of the non-drug treatment options that fall under cognitive rehabilitation:
- Cognitive stimulation therapy (CST): Involves joining group activities and exercises to improve memory and problem-solving skills for people with mild to moderate dementia. One review suggests that cognitive stimulation programs benefit cognition (Woods, 2012).
- Exercise programs: Several small studies show that exercise programs may improve physical functioning, referring to the ability to perform basic activities of daily living like walking or climbing stairs. However, these studies did not find that exercise programs improved cognitive functioning in adults with dementia (Teri, 2003).
- Occupational therapy: Occupational therapy supports someone’s abilities to remain independent. In one study, those who received 10 sessions of occupational therapy over five weeks had significantly better motor skills and improved activities of daily living, when compared to those who didn’t get the treatment. These improvements were still there three months after the treatment (Graff, 2006).
Alzheimer’s treatment options for behavioral changes
Alzheimer’s disease leads to the death of brain cells (neurodegeneration), and the brain works less well over time. That can affect every aspect of someone’s life; besides memory issues, brain changes can also change how a person acts, sleeps, and how they perceive their own emotions and the world around them.
Common behavioral symptoms of Alzheimer’s disease include (Volicer, 2001):
- Agitation and aggression
- Sleeplessness, restlessness, and wandering
- Anxiety and depression
- Emotional distress
- Delusions (Scarmeas, 2005)
In general, treatments that don’t involve medications are the preferred way to go. That’s because people with Alzheimer’s may experience serious side effects of drugs, occasionally even worsening the symptom being treated. For example, a review of non-drug treatments for agitation found that music therapy, massage, and communication skills training for caregivers can be beneficial, at least in the short-term (Livingston, 2014).
If non-drug treatments don’t work well, healthcare providers might switch to medications.
- Alzheimer’s Association. (2022). 2022 Alzheimer’s disease facts and figures. Retrieved from https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf
- Birks, J. (2006). Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database System Reviews, 1, CD005593. doi:10.1002/14651858.CD005593. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16437532/
- Bloom, G. S. (2014). Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. doi: 10.1001/jamaneurol.2013.5847. Retrieved from https://pubmed.ncbi.nlm.nih.gov/24493463/
- Graff, M. J., Vernooij-Dassen, M. J., Thijssen, M., et al. (2006). Community based occupational therapy for patients with dementia and their care givers: randomised controlled trial. BMJ, 333(7580), 1196. doi:10.1136/bmj.39001.688843.BE. Retrieved from https://pubmed.ncbi.nlm.nih.gov/17114212/
- Livingston, G. & Kelly, L. (2014). Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials. British Journal of Psychiatry, 205(6), 436-442. doi:10.1192/bjp.bp.113.141119. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25452601/
- Scarmeas, N., Brandt, J., Albert, M., et al. (2005). Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Archives of Neurology, 62(10), 1601-1608. doi:10.1001/archneur.62.10.1601. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028538/
- Teri, L., Gibbons, L. E., McCurry, S. M., et al. (2003). Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA, 290(15), 2015-2022. doi:10.1001/jama.290.15.2015 Retrieved from https://pubmed.ncbi.nlm.nih.gov/14559955/
- Volicer, L., Harper, D. G., Manning, B. C., et al. (2001). Sundowning and circadian rhythms in Alzheimer’s disease. American Journal of Psychiatry, 158(5), 704-711. doi:10.1176/appi.ajp.158.5.704. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11329390/
- Woods, B., Aguirre, E., Spector, A. E., et al. (2012). Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database Systematic Reviews (2), CD005562. doi:10.1002/14651858.CD005562. Retrieved from https://pubmed.ncbi.nlm.nih.gov/22336813/
- U.S. Food and Drug Administration (FDA). (2012). ARICEPT ® (donepezil hydrochloride). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020690s035,021720s008,022568s005lbl.pdf
- U.S. Food and Drug Administration (FDA). (2013). NAMENDA (memantine HCl) Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021487s010s012s014,021627s008lbl.pdf
- U.S. Food and Drug Administration (FDA). (2014). NAMZARIC (memantine hydrochloride extended-release and donepezil hydrochloride). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206439lbl.pdf
- U.S. Food and Drug Administration (FDA). (2016). RAZADYNE® ER (galantamine hydrobromide). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021169Orig1s032,021224Orig1s030,021615Orig1s023lbl.pdf
- U.S. Food and Drug Administration (FDA). (2018). EXELON® (rivastigmine tartrate). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020823s036,021025s024lbl.pdf
- U.S. Food and Drug Administration (FDA). (2021). ADUHELMTM (aducanumab-avwa). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s003lbl.pdf
Dr. Chimene Richa is a board-certified Ophthalmologist and Senior Medical Writer/Reviewer at Ro.