Prodromal Alzheimer’s disease explained

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The prodromal stage of Alzheimer’s disease is the period when a person who may develop dementia starts to show mild cognitive impairment.

Researchers show interest in both the prodromal stage of Alzheimer’s disease and the preclinical stages because their new understandings may lead to advancements in treatment and prevention.

Currently, some researchers are studying biomarkers and features of people who have or may develop Alzheimer’s disease.

In a 2020 study, researchers examined how hemoprotein neuroglobin (Ngb) — a substance that is present mainly in the brains of mammals — may play a protective role in the progression of Alzheimer’s disease.

In this study using mice, they found that Ngb levels rose with age in equilibrium with high cerebrospinal fluid amyloid beta (Aß)42 levels. Their findings suggest that the body may produce defense mechanisms against Aß toxicity and that dementia develops as these defense mechanisms wear out or become depleted.

They also noted that in earlier studies, 30–50% of people with typical cognitive ability showed biomarkers of Alzheimer’s disease upon autopsy.

These findings may lead to future treatments in the preclinical and prodromal stages of Alzheimer’s that may help prevent the development of dementia.

The duration of the prodromal stage of Alzheimer’s disease can vary. When considering factors such as age, gender, and setting, the authors of a 2019 study found that age had the biggest influence on the length of Alzheimer’s disease stages.

For example, the predicted disease duration at age 70 years was 20 years. This included:

• 10 years in the preclinical stage
• 4 years in the prodromal stage
• 3 years for mild dementia
• 3 years for moderate dementia

The researchers noted that people at age 60 years had a 24-year disease duration, while those at age 80 years had a 15-year disease duration. The length of each stage also decreased with age.

Cognitive decline may progress throughout the prodromal stage. In an older study from 2011, researchers noted that a person experiences progressively faster cognitive decline in the years leading up to Alzheimer’s disease dementia.

However, more recent studies do not fully agree with this finding. A 2019 study found that people with amnestic mild cognitive impairment progressed at three distinct speeds:

• stable
• slow decliner
• fast decliner

This supports other findings that suggest that not everyone who enters the prodromal stage of Alzheimer’s disease will go on to develop dementia. Some will either revert to a preclinical stage or never progress beyond the point of mild impairments.

However, once a person develops mild Alzheimer’s disease dementia, they will not revert to earlier stages.

The prodromal stage involves mild cognitive impairment.

In one study from 2021, researchers noted that people in the prodromal stage showed behavior changes and decreased executive function. They noted that negative symptoms, which often have an association with withdrawal from the surrounding world, were common. These symptoms included:

• apathy
• loss of insight
• inflexible thinking

The authors of an older review from 2014 suggested that symptoms of prodromal stages of dementia include:

• anxiety
• depression
• irritability
• apathy
• sleep disturbances
• agitation

The National Institute on Aging has identified three symptoms of mild cognitive impairment that may progress to Alzheimer’s disease:

• frequently losing things
• having difficulty finding the right words
• forgetting about important events

Occasionally missing an appointment or a monthly payment, losing things, and forgetting words are all signs of typical aging. However, if these issues happen frequently, a person may want to consult a healthcare professional.

Currently, treatments for the prodromal stage of Alzheimer’s disease are limited to lifestyle strategies and suggestions. Researchers continue to study how diet, environment, and education factor into the development of Alzheimer’s disease.

In a 2017 report that the National Institute on Aging commissioned, researchers found encouraging — but not conclusive — evidence that three preventive measures may be effective for Alzheimer’s disease:

• cognitive training
• blood pressure management in people with hypertension
• increased physical activity

Other studies have looked into certain substances in the body that may play a protective role in Alzheimer’s disease. However, research has not yet explored treatments addressing these substances.

Not everyone who develops mild cognitive impairment will develop Alzheimer’s disease. Future studies on the underlying causes, biological changes, and risk factors may help prevent the development of dementia.

A person should consider seeing a healthcare professional every 6–12 months to track changes in thinking and memory over time. Checkups can help determine whether a person is showing signs of progressing to dementia.

How to cope

People may be able to cope with mild cognitive impairment by:

• using memory tools such as notes, to-do lists, and calendar reminders
• following a daily routine
• trying to learn new skills
• eating a nutritious diet
• avoiding alcohol consumption
• keeping commonly used objects in the same place
• exercising regularly
• finding volunteer opportunities
• getting enough sleep each night
• seeking help for depression
• spending time with friends and family

Alzheimer’s disease is a progressive condition that typically worsens slowly over several years.

Researchers often divide Alzheimer’s disease into three main stages:

• Preclinical: no symptoms, but changes and biomarkers may indicate risk of Alzheimer’s disease progression
• Prodromal: mild cognitive impairment appears
• Dementia: more pronounced cognitive decline

Dementia may further break down into three stages:

• mild
• moderate
• severe

Each successive stage involves worsening cognitive symptoms.

The following sections provide answers to frequently asked questions about Alzheimer’s disease.

What is the difference between preclinical and prodromal Alzheimer’s?

Preclinical stages of Alzheimer’s disease are a period in which a person has no signs or symptoms or has only subjective symptoms, such as mild memory loss. Doctors may be able to identify certain markers that indicate possible development of Alzheimer’s disease, but many people with these markers will not go on to develop the disease.

The prodromal stage involves mild cognitive impairment or decline. A person may notice that they forget things more often, have trouble finding the right words, or forget about appointments or bills.

A person displaying these signs may go on to develop dementia, stay the same, or improve.

What are the 7 stages of Alzheimer’s?

Some organizations classify Alzheimer’s into these seven stages:

• Stage 1: no signs of dementia (preclinical)
• Stage 2: subjective memory loss (preclinical)
• Stage 3: mild cognitive impairment (prodromal)
• Stage 4: mild dementia with moderate cognitive decline
• Stage 5: moderate dementia with moderately severe cognitive decline
• Stage 6: moderately severe dementia with severe cognitive decline
• Stage 7: severe dementia with very severe cognitive decline

The prodromal stage of Alzheimer’s disease is a potentially progressive stage in which a person has signs of mild cognitive decline. A person may experience memory problems and behavioral changes such as apathy and irritability.

Not everyone who enters the prodromal stage will go on to develop dementia. Some may stay the same or see improvements.

No current treatment can cure Alzheimer’s disease or address prodromal symptoms. However, a person can take steps to help improve their functioning in daily life, such as by setting reminders, putting things back in the same place, and getting regular exercise.

Future studies may identify more risk factors and potential preventive measures to stop the development of dementia in people who are at risk.

Anyone who is experiencing frequent issues with memory should consult a healthcare professional.