Disability, older age at start of DMT linked to worse cognition in RMMS

Older age and greater physical disability when starting a disease-modifying therapy (DMT) were linked to worse cognitive function for relapsing-remitting multiple sclerosis (RRMS) patients, but cognition remained relatively stable over the next several years, according to a Swedish study.

Due to the high rates of DMT switches and discontinuations, no associations could be made between specific medications and cognition in these patients.

The findings overall emphasize, “the importance of early diagnosis and intervention to maintain cognitive functions in RRMS,” the scientists wrote.

The study, “Trajectories of cognitive processing speed and physical disability over 11 years following initiation of a first multiple sclerosis disease-modulating therapy,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.

Cognitive impairment is one of the most common MS symptoms, believed to affect somewhere between 40%-70% of patients, and is reported to be correlated with physical disability accumulation.

Particularly, processing speed is often affected, impacting patients’ abilities to quickly and accurately process information as they go about daily life.

Yet, there is a lack of data related to how cognition changes over time in MS patients, the risk factors for decline, and the effects of DMTs on cognitive trajectories.

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Now, researchers in Sweden have investigated the trajectories of cognitive processing speed and physical disability over time among 1,645 adult RRMS patients after starting their first DMT.

Clinical data from these patients came from COMBAT-MS (NCT03193866), a large, population-based observational study of MS patients who started a new DMT at Swedish clinics between 2011-2018. Information from COMBAT MS was cross-linked with the Swedish MS registry and other national health databases.

These 1,645 people were followed for an average of 7.1 years in the period between 2011 and 2022. They had started their first DMT about one year after their MS diagnosis.

Processing speed was evaluated with the Symbol Digit Modalities Test (SDMT), a standard cognitive assessment in the clinic. Throughout follow-up, processing speed was found to be relatively stable in patients, who generally maintained their starting cognitive abilities over time.

Patients were sorted into five trajectories based on their SDMT scores — low (5.4%), low/medium (25.3%), medium (37.9%), medium/high (25.8%), and high (5.6%) — with higher scores reflecting better cognitive function.

In all but the lowest trajectory group, SDMT performance saw a slight uptick in the first five years after DMT initiation, but decreased subsequently over time. Thus, while those in the high SDMT group were found to have clinically meaningful increases in SDMT scores between years 2.3-4.6, this difference did not remain by the end of follow-up.

Disability, as assessed by the Expanded Disability Status Scale (EDSS), followed three distinct trajectories in the patient group. While 26.8% maintained no disability, 58.1% maintained minimal disability, and 15.1% increased from moderate to severe disability over the course of the study.

Starting four years after DMT initiation, the transition from moderate to severe disability was considered a clinically relevant change, defined as more than a 1-point difference on the EDSS scale.

There was overall a strong association between SDMT and EDSS trajectories. The highest probability of belonging to the moderate physical disability group was in patients belonging to the lowest SDMT trajectory.

“This is the first study to show that the link between processing speed and physical disability in patients with MS is not restricted to baseline [starting] values but seems to progress in parallel for several years over the course of the disease,” the researchers wrote.

Moderate disability factors

Participants older than 34 when starting DMTs were significantly less likely to belong to the highest three cognitive trajectories than to the lowest one compared with younger patients. They also were more likely to have minimal or moderate disability trajectories than no disability when compared with patients ages 18-29.

Other factors associated with moderate disability relative to no disability included more than one coexisting condition and a history of pain treatment compared with no coexisting conditions and no history of pain treatment, respectively.

Some links between the starting DMT and cognitive or disability trajectories were observed, but the scientists noted that over the course of follow-up, DMT switches and discontinuations were frequent.

Thus, “we deemed it futile to interpret our results in light of a possible long-term effect of specific DMTs on processing speed trajectories,” the team wrote.

“Further research is needed to better understand the underlying mechanisms and identification of high-risk individuals with low processing speed at RRMS diagnosis,” the scientists concluded.