Speech Analysis in ALS Patients

Cognitive dysfunction is increasingly recognized as a core feature of amyotrophic lateral
sclerosis (ALS). With appropriate testing, up to 50% of ALS patients will show evidence of
frontotemporal dysfunction. Approximately 15% of patients meet formal criteria for
frontotemporal dementia (FTD). Certain genetic forms of ALS (e.g., mutations in C9orf72) have
even higher incidences of FTD. The presence of cognitive abnormalities is an adverse risk
factor for survival, and its presence influences the ability of patients to cooperate in
clinical trials. However, screening for frontotemporal abnormalities is frequently not
performed in ALS clinics, and tools for diagnosing cognitive dysfunction are either time
consuming or insensitive. Additionally, the frequently co-existing dysarthria complicates the
assessment and may mask more subtle cognitive deficits. Once identified, ways of following
progressive decline are also lacking. In an ongoing study, it has been shown that a
sophisticated suite of speech and language analytics, developed by two of the investigators,
can identify abnormalities in cognitively normal ALS patients without speech symptoms, and
predict important functional changes outside of the speech domain. In this study,
investigators will evaluate both speech and language in 50 patients with ALS both with and
without symptoms of cognitive decline. This evaluation will be paired with two cognitive
screening tools frequently used in ALS clinics, the ALS Cognitive Behavioral Screen (ALS-CBS)
and the Montreal Cognitive Assessment (MoCA). The investigators will evaluate the extent to
which speech and language deficits precede abnormalities as measured by the above tools and
determine whether cognitive change can be accurately followed over 12 months using speech and
language measures. It is hypothesized that speech and language measures will accurately and
sensitively predict cognitive changes. If so, such measures may be very useful in future
studies of potential therapeutic agents for ALS-FTD and other dementias.

Inclusion Criteria:

1. male or female, age 21 or older,

2. diagnosed with definite, probable, or possible ALS according to the modified El
Escorial Criteria,

3. a score of 2 or greater on the speech question of the ALSFRS-R (i.e. speech is
intelligible with occasional repetition),

4. continuous internet access at home,

5. willingness and medical ability to comply with scheduled visits and study procedures,

6. ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (PHI) in
accordance with national and local subject privacy regulations,

7. geographic accessibility to study site,

8. for the 25 participants in Group 1, NO noted symptoms of frontotemporal cognitive
dysfunction, and

9. for the 25 participants in Group 2, MUST have cognitive symptoms as noted either by
themselves or a caregiver.

Exclusion Criteria:

1. unwilling or unable to comply with the requirements of this protocol, including the
presence of any condition (physical, mental, or social) that is likely to affect the
participant's ability to comply with the protocol, and

2. any other reasons that, in the opinion of the PI, cause the candidate to be deemed
unsuitable for entry into the study.