Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are diseases that affect the neurological system. Research has found that the genes and genetic components that play a role in both conditions are similar.

This article discusses the connection between ALS and FTD, the risks associated with developing both conditions simultaneously, and what medical providers can do to help manage the comorbidity in patients with both. 

Connection Between ALS and Frontotemporal Dementia

ALS and FTD are considered neurodegenerative diseases. That means that the neurological system and neurons (nerve cells) are affected. Both conditions develop because motor neurons, the cells that aid in movement, become damaged or destroyed.

In the case of ALS, motor neurons found in the frontal cortex, brainstem, and spinal cord are affected. In FTD, the motor neurons in the frontal and temporal lobes of the brain are damaged.

Researchers have examined why the overlap exists between the two conditions and found that it all comes down to genetics. People with ALS or FTD seem to have genetic changes in specific genes, such as:

• C9ORF72
• TARDBP
• FUS
• CHCHD10
• TBK1
• VCP
• SQSTM1

All of these genes provide specific instructions to cells in the body to create the appropriate proteins that aid in bodily functions. When those cells experience changes or mutations, the guidance given to cells is skewed.

The most notable gene association is the C9ORF72 gene. It gives cells the information they need to create a protein found in nerve cells, the same nerve cells that are negatively affected by both ALS and FTD.

Symptoms

Having both conditions can make day-to-day life that much more challenging. People with ALS tend to lose their mobility due to muscle weakness, tightness, stiffness, cramps, speech difficulties, and muscle twitches. These symptoms worsen over time because it is a progressive and fatal disease.

However, it is not always common for those with ALS to experience cognitive changes that occur in FTD, such as:

• Dramatic behavioral and personality changes
• Impulsive or repetitive behaviors that are inappropriate
• Apathy and lack of empathy
• A decrease in self-awareness
• Impaired judgment
• Loss of interest, motivation, and social needs
• Inability to speak or understand when spoken to
• Talking less or feeling hesitant to speak
• Getting distracted easily and having difficulty with organization and planning
• Mood changes, including agitation

Because of that, experiencing mobility symptoms as well as cognitive symptoms at the same time can be highly debilitating for people who develop ALS and FTD simultaneously.  

Risks

Though ALS and FTD are connected, researchers have yet to determine if having one puts a person at a higher risk of developing the other. The two simply share a genetic risk factor.

That said, research has determined that as many as 50% of people with ALS will also develop FTD-based cognitive impairment, and 30% of people with FTD will develop the same motor dysfunction symptoms found in ALS. When people have both conditions, it is referred to as ALS-FTD.

Treatment and Management

Because FTD and ALS are considered neurodegenerative, treatment and management of the diseases focus on slowing down the damage to the affected neurons. That said, there are limited options for people with both.

Research has found that the typical medications for managing FTD and similar diseases that affect the frontotemporal lobes of the brain, such as antidepressants, antipsychotics, and cholinesterase inhibitors, show minimal promise in reducing symptoms. New therapeutic options, such as disease-modifying drugs, are being explored as a possible FTD treatment.

Riluzole is a disease-modifying medication that can help slow the progression of ALS. Still, it is not yet determined whether it can help reduce the symptoms of FTD. Other than that, speech therapy can help with both conditions.

Studies have explored lithium's effects on ALS and FTD and found that it could be a viable treatment option for those with both conditions.   

Summary

ALS and FTD are both neurodegenerative diseases that affect motor neurons. However, the area where those motor neurons are found differs between the two conditions, which is why the symptoms present so differently.

Though it’s unclear whether having one makes it more likely to have the other, 30–50% of people with ALS or FTD will develop both conditions. Researchers have found that the connection between the two, besides the neurological link, comes down to genetics.

Specific gene changes in ALS are also found in FTD, which can explain why the motor neurons are targeted in both conditions. When a person has both, the best thing they can do is find proper treatment. Many medications are available for FTD, but they are not always effective. The options for ALS are also limited, but ongoing research continues to search for better therapies to slow the progression of ALS and reduce symptoms of FTD in people with both diseases.