Charting the Course: A Clear Guide to Alzheimer's Treatment by Stage

Alzheimer's disease can be a difficult diagnosis to hear. However, it's important to know that there are some treatment options available. They may alleviate symptoms or slow the progression of the disease. There's also a lot of ongoing research into new medicines. And a lot of alternative actions you can take beyond medicines.

Hopefully, in a few years, we'll be able to change the course of Alzheimer's or cure it completely. In the meantime, we've summarized below the most common (and some new) Alzheimer's treatments per stage. 

What is Alzheimer's disease?

Alzheimer's disease is a progressive neurological disorder. It impacts memory, thinking, and behavior. It's characterized by the loss of brain cells and the buildup of abnormal protein clusters known as amyloid beta plaques ^[1].

Genetics may be a factor in the development of Alzheimer's disease. However, a family history of Alzheimer's isn't a verdict. According to research, lifestyle factors seem to play a significant role in the development of Alzheimer's ^[1].

The first symptoms of the disease usually start showing after the age of 60. However, changes in the brain related to Alzheimer's usually have begun years earlier ^[4]. 

Although rarely, it's also possible to develop Alzheimer's disease at a younger age. This is known as early-onset Alzheimer's ^[2]. 

What is early-onset Alzheimer's?

It's when a person under the age of 65 gets diagnosed with Alzheimer's disease. This is the case for about 5.5% of all Alzheimer's patients. 

In the United States, diagnosis rates for early-onset Alzheimer's have doubled between 2013 and 2017. Some research shows that women may be more likely than men to get an early-onset Alzheimer's diagnosis ^[3].

If forgetfulness or other symptoms appear in a young person, these may often be dismissed. That's why awareness of early-onset Alzheimer's is important. Especially for people with a family history of early diagnoses. Detecting the disease early on can make a big difference in managing its progression. 

Alzheimer's treatment by stage

Preclinical Alzheimer's

This is the period before someone starts showing symptoms of cognitive decline. At this point, changes in the brain are already happening. Preclinical Alzheimer's can last for years or decades, before the first noticeable symptoms appear ^[6]. 

As it's impossible to diagnose Alzheimer's without any symptoms, it's unlikely that you receive any treatment at this point.

Early-stage Alzheimer's (mild Alzheimer's)

In this early stage of the disease, people are still very independent. The first symptoms they experience are usually memory lapses. Especially when trying to remember words or locations. Other early indications of Alzheimer's can be issues with short-term memory (e.g. forgetting something you've just read), or difficulties with planning and organizing ^[4]. Mood changes and withdrawn behaviour are also common in this stage ^[6]. 

How long you will stay in the early stages of the disease can vary greatly. Typically, mild Alzheimer's lasts about two years before it progresses ^[5].  

Treatment of early-stage Alzheimer's

Early-stage Alzheimer's disease treatment focuses on delaying cognitive deterioration and improving brain health. Treatment options may include:

• Cholinesterase inhibitors (ChEIs). Some of the commonly used cholinesterase inhibitors are galantamine, rivastigmine, and donepezil. They prevent the breakdown of acetylcholine. Acetylcholine plays a role in memory and thinking. As Alzheimer's progresses, less of it is produced by the brain. Unfortunately, ChEIs become less effective over time ^[7]. 
• Anti-amyloid therapy. Three new anti-amyloid therapies have been approved by the FDA in the USA since 2021. These therapies are Leqembi (lecanemab), Aduhelm (aduhanumab), and Kisunla (donanemab). All three are monoclonal antibodies and are designed to target and remove beta-amyloid plaques. In this way, Leqembi, Aduhelm, and Kisunla aim to slow down the disease progression, rather than only addressing symptoms. All three medicines have a similar way of working, although there are some differences ^[7]. 

Moderate to moderately severe Alzheimer's

In this stage, people start to experience more difficulties with their daily activities. They may struggle to remember major events, weather conditions, as well as their own address. Counting backwards and taking care of financial tasks becomes difficult at this stage. General issues with orientation can also worsen ⁶. 

As the disease progresses further, people start struggling to maintain personal hygiene and get dressed independently. They may start sleeping less and wandering at night. Feelings of shame, frustration, and the fear of being alone are typical for this stage of the disease[6].

Moderate Alzheimer's lasts approximately 1-2 years, before it progresses towards moderately severe Alzheimer's. Moderately severe Alzheimer's lasts for another 2-3 years. The duration of these periods can vary from one patient to another [6]. 

Treatment of moderate and moderately severe Alzheimer's

Typical treatment approaches in this stage of Alzheimer's focus on alleviating symptoms. The goal is to help people maintain daily functions as long as possible. Some of the medicines that can support with that are:

• Cholinesterase inhibitors (ChEIs). Some ChEIs can also be used in this stage of Alzheimer's. These include donepezul and rivastigmine [7].
• Memantine, and other N-methyl-D-aspartate (NMDA) antagonists. These medicines regulate glutamate, an important brain chemical. Overproduction of glutamate may be related to brain cell death. NMDAs work differently from cholinesterase inhibitors. This allows both types of medicines to be used together [7].

Severe Alzheimer's 

This stage of the disease is characterized by progressive loss of speech, movement, and independence. Towards the end of this stage, people often become immobile. The most common cause of death in this stage of Alzheimer's is pneumonia ^[6].

Severe Alzheimer's usually lasts about 1.5-2.5 years, which may vary in individual cases ^[6].

Treatment of severe Alzheimer's

In this advanced stage of Alzheimer's, typically the same treatments apply as in the moderate and moderately severe stage. Treatment options may include NMDA antagonists or cholinesterase inhibitors. Or, a combination of both types of medicines ^[7]. 

At this or earlier stages of the disease, medicines for specific symptoms may be prescribed. For example, antidepressants, antipsychotic (neuroleptic) medications, insomnia medications, or others ^[8].

Alzheimer's treatment beyond medicines

There are various approaches beyond medicines that can support your treatment. 

Behavioral interventions

Behavioral interventions are crucial for managing behavior changes in individuals with Alzheimer's disease. These interventions aim to keep the person comfortable in their environment and effectively manage cognitive and behavioral manifestations of the disease.

One important behavioral intervention is creating a calm and structured environment. This involves reducing noise, clutter, and distractions that may agitate the individual. Establishing a daily routine and engaging the person in familiar tasks can provide a sense of stability and promote a sense of comfort.

Therapies such as art or music therapy, social activities and support groups can also help reduce feelings of isolation ^[13].

Lifestyle interventions

In parallel to any treatment with medication, the adoption of healthy habits is always recommended.

Some studies suggest that following the Mediterranean or MIND diet is associated with cognitive benefits. Although there is no definitive proof of this connection yet, it's a zero-risk lifestyle intervention that anyone can adopt. Some clinical trials studying the effects of diet on brain health are ongoing ^[10]. 

Physical activity may also play a role in improving cognitive function, especially in early Alzheimer's patients ^[11]. This may be related to the hormone irisin, which muscles secrete during exercise. Some early animal studies show that irisin may protect against neuroinflammation. Neuroinflammation is the biggest killer of brain neurons as we age, according to Rudolph Tanzi, Professor of Neurology at HMS ^[12]. 

Final words on Alzheimer's treatment options

As a complex disease, Alzheimer's warrants a complex treatment. You're likely going to have to address Alzheimer's from different angles.

Medicines are just one aspect of Alzheimer's treatment. Another requires lifestyle improvements, such as a healthy diet and regular physical activity. Last but not least, it's important to attend to your mood and mental wellbeing. Support groups and therapy can help the battle with Alzheimer's feel less isolating.

As we hope for more breakthroughs in Alzheimer's treatment, it's important to remember that Alzheimer's is going to affect more and more people in the rapidly aging societies around the world. Whatever side of the story you're on now, we're all in this fight together.

References:

1. What is Alzheimer's Disease? Centers for Disease Control and Prevention, Accessed 14 July 2023.
2. Rate of early onset Alzheimer's disease: a systematic review and meta-analysis. NCBI, Accessed 14 July 2023.
3. Keck, Kim. Early-Onset Dementia and Alzheimer's Rates Grow for Younger American Adults. Blue Cross Blue Shield, 27 February 2020.
4. Alzheimer's Stages - Early, Middle, Late Dementia Symptoms. Alzheimer's Association, Accessed 14 July 2023.
5. Early-stage signs and symptoms of dementia. Alzheimer's Society, 24 February 2021, Accessed 14 July 2023.
6. Biggers, Alana. What Are the Stages of Alzheimer's Disease?. Healthline, Accessed 14 July 2023.
7. How Is Alzheimer's Disease Treated?. National Institute on Aging, 1 April 2023, Accessed 14 July 2023.
8. Treatments for Behavior. Alzheimer's Association, Accessed 14 July 2023.
9. Reducing Risk of Alzheimer's Disease. Centers for Disease Control and Prevention, Accessed 14 July 2023.
10.  What Do We Know About Diet and Prevention of Alzheimer's Disease?. National Institute on Aging, 27 November 2019.
11. Jiang, Jiehui. Relationship Between Exercise and Alzheimer's Disease: A Narrative Literature Review. NCBI, 26 March 2020.
12. Young, Randy. Exercise and Alzheimer's Disease. Harvard Medical School, 25 August 2021, Accessed 14 July 2023. 
13. Behavioral Approaches in Dementia Care. Practical Neurology, Accessed 14 July 2023.