  Health-related quality of life (Hr-QoL) scales provide crucial information on
neurodegenerative disease progression, help improving patient care, and
constitute a meaningful endpoint for therapeutic research. However, Hr-QoL
progression is usually poorly documented, as for multiple system atrophy (MSA),
a rare and rapidly progressing alpha-synucleinopathy. This work aimed to
describe Hr-QoL progression during the natural course of MSA, explore
disparities between patients, and identify informative items using a four-step
statistical strategy.We leveraged the data of the French MSA cohort comprising
annual assessments with the MSA-QoL questionnaire for more than 500 patients
over up to 11 years. The four-step strategy (1) determined the subdimensions of
Hr-QoL in MSA; (2) modelled the subdimension trajectories over time, accounting
for the risk of death; (3) mapped the sequence of item impairments with disease
stages; and (4) identified the most informative items specific to each disease
stage.Among the 536 patients included, 50% were women and they were aged on
average 65.1 years old at entry. Among them, 63.1% died during the follow-up.
Four dimensions were identified. In addition to the original motor, nonmotor,
and emotional domains, an oropharyngeal component was highlighted. While the
motor and oropharyngeal domains deteriorated rapidly, the nonmotor and
emotional aspects were already slightly to moderately impaired at cohort entry
and deteriorated slowly over the course of the disease. Impairments were
associated with sex, diagnosis subtype, and delay since symptom onset. Except
for the emotional domain, each dimension was driven by key identified
items.Hr-QoL is a multidimensional concept that deteriorates progressively over
the course of MSA and brings essential knowledge for improving patient care. As
exemplified with MSA, the thorough description of Hr-QoL using the 4-step
original analysis can provide new perspectives on neurodegenerative diseases'
management to ultimately deliver better support focused on the patient's
perspective.
