“Give physical and cognitive symptoms equal attention in MS”

Prof. Maria Pia Amato (University of Florence, Italy) delivered the ECTRIMS Lecture at the 2025 meeting, where she discussed progress and perspectives in the management of cognitive function in multiple sclerosis (MS), aiming to encourage clinicians to focus equally on both physical and cognitive symptoms. “It makes a huge difference for our patients,” she noted.

Prof. Amato was among the very first researchers to monitor cognitive changes over time in adults and children, and to connect these changes to brain pathology. She stressed that in a time when early and highly effective MS treatments are available, cognitive symptoms remain a considerable concern for many patients. In the Global Patient-Reported Outcomes in MS (PROMS) survey, the most common symptoms reported by over 5,200 patients from 69 countries were: fatigue (86%), stress (80%), pain (75%), concentration problems (75%), and memory problems (74%) [2]. The prevalence of cognitive impairment in MS ranges from 30% to 65%. Key domains affected are complex attention (with a particular focus on processing speed), learning and memory, and working memory. Cognitive impairment is not limited to the later stages of MS; in a study across MS subtypes, 46% of participants had cognitive impairment [3]. Rates were highest in primary and secondary progressive MS, but even in participants with only a clinically isolated syndrome, the rate was as high as 35% (see Figure). Prof. Amato was intrigued that even in pre-clinical MS patients with a radiologically isolated syndrome, 24% had cognitive changes [4].

Figure: Cognitive impairment as a function of MS stage [1].



CIS, clinically isolated syndrome; MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; PPMS, secondary progressive multiple sclerosis.  

Cognitive deficits in childhood are associated with long-term consequences, for example, in work and social attainment [5]. Results of a very recent study of 63 paediatric MS patients were more positive: after 2 years, 80% were either stable or improved [6]. This could, in part, reflect positive effects of earlier diagnosis, earlier intervention, and increasing use of high-efficacy drugs in this population, Prof. Amato reported. On average, the brains of MS patients look 10 years older than those of healthy controls, she added [7]. There are different ways in which cognitive impairment can progress in MS: through isolated cognitive relapses (which can occur without physical symptoms), and cognitive progression independent of relapse activity (and MRI activity) (PIR[M]A). Cognitive PIR(M)A has been recently established as a concept in a study, where 68% of MS patients showed cognitive decline, independent of worsening on the Expanded Disability Status Scale (EDSS) [8]. “This is why we may need to incorporate cognition in the broader concept of PIRA,” explained Prof. Amato. This highlights the need for regular cognitive monitoring and to use the same methods and definitions. To this end, the joint ECTRIMS-IMSCOGS Guidelines (International Multiple Sclerosis Cognition Society) project was set up.

Cognitive impairment in MS has multifactorial causes, including white matter damage and lesions, grey matter atrophy, and dysfunction of the functional network. In people with and without MS alike, cognitive reserve can protect against decline. Identifying cognitive phenotypes can help tailor interventions to individual needs. A study in 1,212 MS patients identified 5 phenotypes: preserved cognition (19%), mild verbal memory/semantic fluency issues (30%), mild multi-domain issues (19%), severe attention/executive issues (14%), and severe multi-domain issues (18%) [9]. Management approaches for cognitive impairment that Prof. Amato mentioned included disease-modifying treatments, which have minor positive effects on cognition, cognitive rehabilitation, memory rehabilitation, and rehabilitation-induced neuroplasticity confirmed by imaging. Among emerging approaches are computerised training, gamification, mindfulness and meditation, and combined physical and cognitive training.

Prof. Amato advocated to “make cognition visible in routine MS care,” by using digital tools for monitoring, prioritising cognition in clinical trials, and developing evidence-based, tailored rehabilitation.

1. Amato MP. Cognitive function in multiple sclerosis: progress and perspectives. PS1, ECTRIMS 2025, 24–26 September 2025, Barcelona, Spain.
2. Brichetto G, et al. Manuscript in preparation.
3. Ruano L, et al. Mult Scler. 2017;23(9):1258–1267.
4. Amato MP, et al. Neurology. 2012;78(5):309–314.
5. Portaccio E, et al. Neurology. 2022;98(16):e1626–1636.
6. O'Neill KA, et al. Neurology. 2025;105(8):e214142.
7. Pontillo G, et al. Neurology. 2024;103(10):e209976.
8. Fuchs T, et al. Mult Scler. 2024;30(11-12):1468–1478.
9. De Meo E, et al. JAMA Neurol. 2021;78(4):414–425.

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Posted on 25 November 202525 November 2025