Clinicians, researchers, family members and patients have long known that people with amyotrophic lateral sclerosis (ALS) sometimes display cognitive and behavioral symptoms. However, only in the last decade or so has it been officially recognized that ALS, like some other motor neuron diseases, affects thinking and behavior. 

Today, we understand ALS as a multisystem disorder. The discovery that a mutation in the C9orf72 gene can cause both ALS and frontotemporal dementia (FTD) confirmed that ALS is not solely a movement disorder.1,2 However, the causes of dementia in people with ALS remain largely unknown.3

 

ALS cognitive symptoms

Dementia associated with ALS typically causes only mild symptoms — ones that may go unnoticed except by those closest to the person with ALS.4

The decline in social cognition and executive and verbal memory functions we see in some people with ALS cannot be blamed on physical deterioration alone.5 In fact, a 2020 study found a progression of cognitive and/or behavioral impairment in more than one-third of patients with early-stage ALS.6

Other research suggests that about half of ALS patients demonstrate mild to moderate cognitive and/or behavioral impairment, and about 10% to 20% of ALS patients meet the criteria for dementia. Roughly 30% of ALS patients develop impairment without dementia, and up to half of ALS patients are cognitively normal.7,8,9

Does ALS affect memory? Yes, to a degree. Some memory problems develop in about half of patients diagnosed with ALS, but they are often mild. For instance, ALS doesn’t take away the ability to recognize their loved ones.10,11

Only a relatively small subset of people with ALS has cognitive symptoms that are similar to that seen in frontotemporal dementia. To date, no one knows (with any certainty) why this is.12 Genetics may hold a clue.

 

ALS with frontotemporal dementia

About a third of people with ALS also develop FTD.13 C9orf72 mutations account for 25% to 40% of familial (inherited) ALS cases and about 7% of sporadic cases. Some people with ALS caused by C9orf72 gene mutations develop FTD, a progressive brain disorder that affects personality, behavior and language.14

The C9ORF72 mutation is the most common mutation responsible for both diseases, ALS and FTD, in Europe and the U.S.15,16

Researchers continue to investigate the clinical syndrome where both FTD and ALS occur in the same person, termed ALS-frontotemporal spectrum disorder.17 They are clearly related: ALS and FTD form a broad neurodegenerative continuum. One of the earliest hints of this overlap came from the clinical observation that both disorders can be present within the same family or even within the same individual. Researchers estimate that up to half of those with ALS develop cognitive impairment associated with FTD and that up to 30% of people with FTD develop motor dysfunction.18

 

What is FTD?

FTD isn’t one condition: It’s a group of disorders characterized by the loss of nerve cells in the frontal and temporal lobes of the brain — areas associated with personality, behavior and language. It is the most common form of dementia in individuals under 60. It accounts for approximately 10% to 20% of cases, and like ALS, FTD progresses over time.19,20

 

How Common is FTD with ALS?

It’s sometimes misdiagnosed as a psychiatric problem or as Alzheimer’s disease, especially in more advanced cases. FTD involves extreme changes in behavior and personality. Among them 21,22

  • Loss of inhibition and increasingly inappropriate social behavior
  • Loss of empathy and other interpersonal skills
  • Lack of judgment
  • Apathy
  • Binge eating
  • Repetitive compulsive behavior
  • Poor personal hygiene
  • Eating inedible objects and compulsively wanting to put things in the mouth

 

Looking for answers on ALS, Cognitive Impairment, and Dementia

So far, no specific treatments are available for frontal lobe dementia in ALS. Medications for ALS and other motor neuron diseases don’t appear to improve cognition. Moreover, some drugs used for Alzheimer’s disease may exacerbate some of the dementia symptoms. Antidepressants and dopamine blockers may help with some of the behavioral disturbances.23

Scientists continue to explore dementia in ALS, looking for causes, treatments and even cures. Target ALS supports research into the connections between ALS and FTD. To learn more about our work, visit www.targetals.org.

 

Sources

1 www.theaftd.org/what-is-ftd/ftd-and-als-ftd-als/

2 www.mda.org/alsn/article/when-thinking-parts-brain-go-awry-als

3 www.webmd.com/alzheimers/dementia-amyotrophic-lateral-sclerosis

4 www.mda.org/alsn/article/when-thinking-parts-brain-go-awry-als

5 Cognitive changes predict functional decline in ALS: a population-based longitudinal study. Neurology 2013; 80:1590–7 http://www.ncbi.nlm.nih.gov/pubmed/23553481

6 Beeldman E, Govaarts R, de Visser M, et al Progression of cognitive and behavioural impairment in early amyotrophic lateral sclerosis Journal of Neurology, Neurosurgery & Psychiatry 2020;91:779-780. 

7 www.als.org/navigating-als/resources/fyi-als-cognitive-impairment-dementia

8 http://my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als

9 www.als.org/navigating-als/resources/fyi-als-cognitive-impairment-dementia

10 my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als

11 www.mda.org/alsn/article/when-thinking-parts-brain-go-awry-als

12 www.webmd.com/alzheimers/dementia-amyotrophic-lateral-sclerosis

13 A New Clue in the Mystery of ALS, Frontotemporal Dementia. University of Michigan (2019)

14 C9orf72 gene MedLinePlus

15 Ciura S, Sellier C, Campanari ML, Charlet-Berguerand N, Kabashi E. The most prevalent genetic cause of ALS-FTD, C9orf72 synergizes the toxicity of ATXN2 intermediate polyglutamine repeats through the autophagy pathway. Autophagy. 2016 Aug 2;12(8):1406-8. doi: 10.1080/15548627.2016.1189070. Epub 2016 May 31. PMID: 27245636; PMCID: PMC4968221.

16 https://www.targetals.org/2021/06/15/under-the-microscope-sami-barmada-m-d-ph-d-on-biomarkers-and-therapeutic-targets-for-als/

17 www.theaftd.org/what-is-ftd/ftd-and-als-ftd-als/

18 Abramzon, Y. A. et al.: The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Frontiers in Neuroscience 0 (2020) www.frontiersin.org/articles/10.3389/fnins.2020.00042/full

19 www.hopkinsmedicine.org/health/conditions-and-diseases/dementia/frontotemporal-dementia

20 www.mayoclinic.org/diseases-conditions/frontotemporal-dementia/symptoms-causes/syc-20354737

21 www.mayoclinic.org/diseases-conditions/frontotemporal-dementia/symptoms-causes/syc-20354737

22 www.ucsfhealth.org/conditions/frontotemporal-dementia/symptoms

23 https://www.emedicinehealth.com/dementia_in_als_lou_gehrigs_disease/article_em.htm

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