King's College London and Imperial College London, in collaboration with
the UK MS Register, report a prevalent multiple sclerosis (MS) subtype marked
by significant cognitive deficits with minimal motor impairment, a form of
disability the authors state is currently unrecognized and untreated.
Cognitive problems in MS affect 40–70% of patients, can appear at any
disease stage and across subtypes, and often affect work and quality of life
more than physical impairment.
Standard neuropsychological assessments can be lengthy (several hours long)
or narrowly focused. Cognition is not routinely measured in MS clinical trials where
the focus tends to prioritize more obvious physical signs of the disease.
Absence of reliable routine assessments excludes cognition from being part of
phenotype definitions, making the impact, prevalence and severity of cognitive
deficits unclear.
In the study, "Large-scale online assessment uncovers
a distinct Multiple Sclerosis subtype with selective cognitive
impairment," published in Nature
Communications, researchers optimized and deployed an automated online
assessment to characterize MS-related cognitive deficits at population scale
and to derive symptom-based phenotypes.
A total of 4,526 UK MS Register members participated across three stages.
Stage 1 invited 19,188 registrants, with 3,066 engaging. Stage 2 recorded 2,696
engagements, including 1,425 first-time participants for independent
validation. Stage 3 enrolled 31 patients for in-person comparison with a
standard neuropsychological assessment with trained examiners.
Stage 1 evaluated 22 online tasks on the Cognitron platform to gauge
feasibility and MS discriminability, then selected a 12-task battery based on
effect sizes, device sensitivity, and factor analysis spanning six latent
domains. Accuracy was prioritized as the primary metric for most tasks due to
weaker correlations with motor patient-reported outcomes.
Stage 2 administered the 12-task battery plus two object memory tasks and
replicated discriminability in an independent cohort.
Stage 3 compared the online battery with a comprehensive in-person
assessment and included the Nine-Hole Peg Test to index hand motor function.
Stage 1 and Stage 2 yielded high feasibility of use with over 70% finishing
in a median single sitting of roughly 40 minutes.
Four symptom-based groups emerged when online thinking measures were
combined with two motor questionnaires in Stage 2.
- Minimal Motor + Moderate Cognitive—little day-to-day movement
difficulty paired with clear problems in memory, reasoning, task
switching, and attention. Group size reached 26.0%, with 44.6%
classified as cognitively impaired.
- Minimal Motor + No Cognitive—little movement difficulty and broadly
intact thinking skills, apart from slower performance on a single task. Group size reached
25.5%, with 1% classified as impaired.
- Severe Motor + Mild Cognitive—marked movement difficulty with smaller thinking problems. Group size reached 34.2%, with 28.3% classified as impaired.
- Severe Motor + Severe Cognitive—marked movement difficulty with broad
thinking problems. Group size reached 14.3%, with 98.2% classified as impaired.
Stage 3 put the online battery side by side with an in-person clinic
assessment of 31 people. Results from the two approaches matched closely for
overall cognitive status. Of the 16 people the clinic tests labeled as
cognitively impaired, the online battery identified 75%. Across all
participants, the online battery classified 20 of 31 as impaired.
Authors conclude that a common MS subtype exists with minimal motor disability yet substantial cognitive problems, revealed only with detailed cognitive profiling and that a fully automated, large-scale online assessment is feasible for this selective cognitive subtype that standard motor-focused evaluations miss.
Source: Online testing uncovers a common multiple sclerosis subtype with hidden cognitive deficits
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