Understanding the Journey with ALS: Factors That May Influence Cognitive Progression

If you or a loved one is living with amyotrophic lateral sclerosis (ALS), you know how unpredictable the disease can be. While ALS is best known for affecting movement, many people don’t realize it can also impact thinking, memory, or behavior over time. A recent study published in Annals of Neurology offers new insights into how cognitive function changes in ALS—and which factors might predict who is at higher risk of decline.

This article breaks down what the research found, why it matters for people with ALS, and how you can use this information to have more informed conversations with your care team.

What You’ll Learn

The study focused on 161 adults with ALS followed for one year to track changes in cognitive (thinking) and behavioral function. Researchers wanted to answer two key questions:

1. How many people with ALS develop cognitive or behavioral changes within the first year of diagnosis?
2. What factors (like age, genetics, or test results) might predict who is more likely to experience decline?

The goal isn’t to predict your individual journey—every person with ALS is unique. Instead, the findings aim to help patients and doctors anticipate challenges, tailor care, and empower you to take proactive steps.

A Quick Look at ALS

ALS is a progressive disease that damages the nerve cells (motor neurons) responsible for movement. Over time, this leads to muscle weakness, difficulty speaking, eating, or breathing, and eventually paralysis. While movement is the most visible symptom, up to 50% of people with ALS also experience cognitive impairment—from mild issues with planning or word-finding to more severe conditions like frontotemporal dementia (FTD).

The study highlights that cognitive changes are not “optional” in ALS—they’re a common part of the disease for many, but how and when they occur varies widely.

Why Understanding Cognitive Progression Matters

Learning about factors that influence cognitive decline can:

• Help you and your doctor make informed decisions about care (e.g., when to involve a neuropsychologist or adjust medications).
• Set realistic expectations (while always holding onto hope—progress varies!).
• Highlight areas where you can take action (like building “cognitive reserve” through education or mental stimulation).

The study’s findings are especially important because cognitive decline in ALS is linked to faster motor decline and shorter survival. Catching changes early can improve quality of life for both patients and caregivers.

What Did Researchers Learn About Cognitive Progression in ALS?

The study followed 161 patients with ALS, 107 of whom completed cognitive testing at both diagnosis (T0) and one year later (T1). Here are the key takeaways:

1. Cognitive Decline Is Common—Even in “Cognitively Normal” Patients

• 27% of patients who had no cognitive issues at diagnosis (called “ALS-normal cognition” or ALS-CN) developed cognitive or behavioral changes within a year. This included problems with planning, word-finding, or mood.
• 33% of patients who already had mild cognitive impairment at diagnosis got worse over the year.

2. Two Simple Tests Predict Risk of Decline

Researchers found that verbal fluency tests—which measure how quickly you can think of words starting with a specific letter (e.g., “F,” “A,” “S”)—were the strongest predictors of future cognitive decline. Specifically:

• FAS Test: A score below 28.75 at diagnosis was linked to a higher risk of decline.
• ECAS Verbal Fluency: A score below 14.2 at diagnosis was also a red flag.

These tests are quick, non-invasive, and often used in routine ALS care—meaning they could easily be part of your regular checkups to monitor cognitive health.

3. Age, Education, and Genetics Play a Role

• Older age: Patients over 69 were more likely to experience cognitive decline.
• Lower education: Less formal education (a proxy for “cognitive reserve,” or the brain’s ability to adapt to damage) was linked to higher risk.
• Genetic variants: People with ALS-related gene changes (like C9ORF72, the most common genetic cause of ALS) were 5 times more likely to develop cognitive issues.

4. Brain Imaging Shows Early Clues

For a subset of patients, PET scans (which measure brain activity) revealed:

• Hypometabolism (reduced activity) in the left temporal lobe (an area linked to memory and language) in patients who later developed cognitive decline.
• Hypermetabolism (increased activity) in the cerebellum (a brain region that helps with coordination) in patients whose cognitive function worsened.

These findings suggest that brain changes may occur before symptoms appear—a key insight for early intervention.

What This Might Mean for Managing ALS

The study’s findings offer actionable steps for people with ALS and their care teams:

1. Ask for Regular Cognitive Screenings

Since verbal fluency tests (FAS and ECAS) predict decline, ask your doctor to include them in your routine checkups. Early detection can help you access therapies (like speech or occupational therapy) to manage symptoms.

2. Discuss Genetic Testing

If you have a family history of ALS or FTD, talk to your doctor about genetic testing. Knowing if you carry a variant like C9ORF72 can help tailor your care plan.

3. Build Cognitive Reserve

While education is a fixed factor, you can boost your brain’s resilience by:

• Engaging in mentally stimulating activities (e.g., puzzles, reading, learning a new skill).
• Staying socially connected (isolation can worsen cognitive decline).
• Following a heart-healthy diet (research links diet to brain health).

4. Plan for the Future

If you’re at higher risk of cognitive decline (e.g., older age, low education, genetic variants), work with your care team to:

• Create advance directives (legal documents outlining your care wishes).
• Involve a neuropsychologist early to help manage behavioral changes.
• Connect with support groups for caregivers (cognitive decline can be challenging for loved ones too).

Very Important Considerations

It’s critical to remember:

• This is a group study, not a crystal ball: The findings reflect trends in a large group, but your experience may be very different.
• Attrition bias: 35% of patients couldn’t be re-tested (due to severe illness or death), so the study may underestimate how many people experience decline.
• Medical advances: New treatments (like gene therapies) could change outcomes for future patients.

Cognitive decline is not inevitable—many people with ALS live for years with stable thinking skills.

Key Points to Remember

• 27% of cognitively normal ALS patients develop cognitive/behavioral changes within a year.
• Verbal fluency tests (FAS, ECAS) are simple tools to predict risk.
• Age, education, and genetics influence decline—but there are steps you can take to manage risk.
• Early intervention (e.g., cognitive screenings, therapy) can improve quality of life.

Talk to Your Doctor

The most important step you can take is to have an open conversation with your care team about your cognitive health. Ask:

• “Should I be tested for ALS-related genetic variants?”
• “How often should I get cognitive screenings?”
• “What can I do to protect my thinking skills?”

Your doctor knows your unique history and can help you interpret the study’s findings in the context of your life.

Living with ALS means navigating uncertainty—but research like this gives us more tools to face it with confidence. By understanding the factors that influence cognitive progression, you can take control of your care and focus on what matters most to you.

Remember: You are not alone. Millions of people with ALS, caregivers, and researchers are working together to improve outcomes—and every day brings new hope.