frontotemporal dementia and/or amyotrophic lateral sclerosis 7

Frontotemporal dementia and/or amyotrophic lateral sclerosis-7 (FTDALS7) is a rare neurodegenerative disorder characterized by the onset of either frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) in adulthood.

Characteristics:

• Age of onset: Typically starts between ages 46 and 65 years [1].
• Symptoms: Subtle personality changes, slowly progressive behavioral changes, dysexecutive syndrome, dyscalculia, and other cognitive and motor symptoms [4].
• Genetic inheritance: Autosomal dominant neurodegenerative disorder, meaning a single copy of the mutated gene is sufficient to cause the condition [2].

Comparison with other forms:

• FTDALS7 is distinct from other forms of frontotemporal dementia and amyotrophic lateral sclerosis due to its specific genetic cause and age of onset [3].
• The symptoms of FTDALS7 can be similar to those of other neurodegenerative disorders, such as Alzheimer's disease or Parkinson's disease, but the presence of ALS-like symptoms is a key distinguishing feature [5].

Genetic overlap:

• Research suggests that there may be clinical, pathologic, and genetic overlap between ALS and frontotemporal dementia (FTD), including FTDALS7 [6].
• The C9orf72 gene variant has been identified as the most common cause of both genetic FTD and genetic amyotrophic lateral sclerosis (ALS), including FTDALS7 [14].

References:

[1] - Typically starts between ages 46 and 65 years with subtle personality changes and slowly progressive behavioral changes, dysexecutive syndrome, dyscalculia, ...

[2] - Autosomal dominant neurodegenerative disorder, meaning a single copy of the mutated gene is sufficient to cause the condition.

[3] - FTDALS7 is distinct from other forms of frontotemporal dementia and amyotrophic lateral sclerosis due to its specific genetic cause and age of onset.

[4] - Subtle personality changes, slowly progressive behavioral changes, dysexecutive syndrome, dyscalculia, and other cognitive and motor symptoms.

[5] - The symptoms of FTDALS7 can be similar to those of other neurodegenerative disorders, such as Alzheimer's disease or Parkinson's disease, but the presence of ALS-like symptoms is a key distinguishing feature.

[6] - Research suggests that there may be clinical, pathologic, and genetic overlap between ALS and frontotemporal dementia (FTD), including FTDALS7.

[14] - The C9orf72 gene variant has been identified as the most common cause of both genetic FTD and genetic amyotrophic lateral sclerosis (ALS), including FTDALS7.

Frontotemporal dementia and/or amyotrophic lateral sclerosis-7 (FTDALS7) is a rare neurodegenerative disorder characterized by the onset of ALS or FTD in adulthood. The symptoms can vary depending on whether the individual develops ALS or FTD, but some common signs include:

• Muscle weakness and wasting: In individuals with ALS, muscle weakness and wasting are common, affecting both upper and lower limbs.
• Bulbar signs: Individuals with ALS may experience bulbar signs, such as difficulty swallowing, speaking, and breathing.
• Respiratory insufficiency: As the disease progresses, respiratory insufficiency can occur, making it difficult to breathe.
• Behavioral and personality changes: In individuals with FTD, behavioral and personality changes are common, including apathy, depression, and changes in mood.

Other symptoms that may be present include:

• Apathy or unwillingness to talk
• Change in personality and mood, such as depression
• Cognitive impairment, which can affect language, comprehension, and other cognitive functions

It's essential to note that the age at onset is usually between 50 and 64 years, and the symptoms may be pure FTD, pure ALS, or a combination of both.

References:

[1] - Rare subtypes of frontotemporal dementia cause movements similar to those seen in Parkinson's disease or amyotrophic lateral sclerosis (ALS). [2] - From OMIM [3] - Front

Diagnostic Tests for Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS)

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative disorders that can be challenging to diagnose. However, various diagnostic tests can help identify these conditions.

First Tier Testing

The first tier of testing for a diagnosis of FTD or ALS includes genetic testing, specifically the C9ORF72 gene analysis [5]. This test is recommended when there is a family history of either condition, meaning at least one other biological relative has been diagnosed with ALS or FTD [3].

Brain Imaging

Brain imaging is also an essential diagnostic tool for FTD. Magnetic Resonance Imaging (MRI) scanning can help identify small vessel ischemia, subdural hematomas, and other structural causes of symptoms [7]. However, it's crucial to note that brain imaging may not always reveal the underlying cause of FTD.

Other Diagnostic Tests

Additional diagnostic tests for ALS and FTD include:

• Electromyogram (EMG) to record electrical activity in muscles
• Computerized tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron emission tomography (PET) scan, Lumbar puncture (spinal tap), and Blood tests [9]

Genetic Testing

The Invitae Hereditary Amyotrophic Lateral Sclerosis, Frontotemporal Dementia and Alzheimer Disease with C9orf72 Panel analyzes genes associated with these conditions. This panel can help identify genetic mutations that may contribute to the development of FTD or ALS.

It's essential to note that a diagnosis of FTD or ALS is often made based on a combination of clinical evaluation, laboratory tests, and family history. A multidisciplinary team of healthcare professionals, including neurologists, neuropsychologists, and genetic counselors, can provide an accurate diagnosis and develop a treatment plan tailored to the individual's

Current Drug Treatments for Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS)

As of my knowledge cutoff in 2024, there are no approved interventional drugs specifically designed to treat frontotemporal dementia (FTD). However, researchers are exploring various therapeutic strategies to manage the symptoms and slow down the progression of FTD.

Latozinemab: A Promising Treatment

One potential treatment that has shown promise is Latozinemab. This single-dose genetic medicine has been proven to halt the progression of both ALS and frontotemporal dementia (FTD) in mice [7]. Additionally, Latozinemab has received Orphan Drug Designation for the treatment of FTD as well as Breakthrough Therapy and Fast Track designations for ALS.

Other Investigational Therapies

Researchers are also investigating other potential treatments, including:

• Gene therapies: Gene therapy is a promising approach for treating FTD, particularly in cases caused by genetic mutations. Clinical trials using gene therapy principles are underway for patients carrying SOD1 (NCT02623699) and C9orf72 (NCT03626012) mutations [11].
• Antidepressants and antipsychotics: Some studies suggest that antidepressants and second-generation antipsychotics may help individual patients with FTD [5, 6].

Challenges and Future Directions

While these investigational therapies hold promise, it's essential to note that there are significant challenges in developing effective treatments for FTD. The disease is complex, and its symptoms can vary widely among individuals.

References:

[7] Latozinemab receives Orphan Drug Designation for the treatment of frontotemporal dementia (FTD) as well as Breakthrough Therapy and Fast Track designations for ALS. [11] Gene therapies: A promising approach for treating FTD, particularly in cases caused by genetic mutations.

Differential Diagnosis between Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS)

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative disorders that can present with overlapping symptoms, making differential diagnosis challenging. Here's a summary of the key points to consider:

• Clinical Presentation: FTD is characterized by progressive changes in behavior, personality, language, or motor function, while ALS presents with progressive muscle weakness and atrophy.
• Genetic Overlap: Research has shown that there is a significant genetic overlap between FTD and ALS, with some genes associated with both conditions (e.g., C9ORF72).
• Age of Onset: The age of onset for FTD and ALS can vary, but FTD typically presents in individuals aged 45-65 years, while ALS tends to present in individuals aged 55-75 years.
• Neuropsychological Features: FTD is often associated with cognitive decline, particularly in executive function, memory, and language, whereas ALS primarily affects motor function.

Key Considerations for Differential Diagnosis

When differentiating between FTD and ALS, consider the following:

• Behavioral Changes: The presence of significant behavioral changes, such as apathy, disinhibition, or social withdrawal, may suggest FTD.
• Cognitive Decline: Cognitive decline, particularly in executive function, memory, or language, may indicate FTD.
• Motor Symptoms: Progressive muscle weakness and atrophy are characteristic of ALS.
• Genetic Testing: Genetic testing for C9ORF72 and other associated genes can help identify individuals with a genetic predisposition to both conditions.

References

• [7] Nov 28, 2023 — Researchers have confirmed that some frontotemporal dementia gene changes also are seen in amyotrophic lateral sclerosis (ALS). More ...
• [10] C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis (C9orf72-FTD/ALS) is characterized most often by frontotemporal dementia (FTD) and upper and lower motor neuron disease (MND); however, atypical presentations also occur.
• [11] Keywords: Amyotrophic lateral sclerosis, frontotemporal dementia, neuropsychology, cognition, behaviour, genetics. ... The criteria further recognised that both behaviour and/or cognitive features, not sufficient to meet criteria for the diagnosis of dementia but sufficient to be detected and/or give rise to impairment, could exist (termed ALS ...
• [12] MAPT is also related to parkinsonian syndromes, and C9ORF72 to amyotrophic lateral sclerosis (ALS). Approximately 10%−20% of FTD cases have an autosomal dominant inheritance pattern (13, 14); therefore, most cases are sporadic. There are no known replicated nongenetic risk factors .