Cognitive impairment is a significant challenge in Multiple Sclerosis (MS), impacting patient well-being. This update introduces a new framework for classifying cognitive impairment in MS, based on five distinct phenotypes defined by both the severity of impairment and the number of cognitive domains affected.

Moving Beyond Domain Types: Introducing Severity-Based Phenotypes:

• Traditional approaches often focus on the type of cognitive domain affected (e.g., memory, executive function) while new research classifies MS patients into five cognitive phenotypes based on severity and breadth of impairment:

·  Preserved Cognition (PC): 56% of patients exhibited no significant cognitive impairment.

·  Mild Single-Domain Impairment (MSD): 15% had mild impairment (1.5 standard deviations below the normative mean) in one cognitive domain.

·  Mild Multi-Domain Impairment (MMD): 9% showed mild impairments across multiple cognitive domains.

·  Significant Single-Domain Impairment (SSD): 12% experienced significant impairment (2 standard deviations below the normative mean) in a single cognitive domain.

·  Significant Multi-Domain Impairment (SMD): 8% had significant impairments spanning multiple cognitive domains.

 

• These phenotypes differ significantly in their demographic, clinical, and MRI characteristics.

 

 

 

 

 

 

 

Understanding the Phenotypes: Characteristics and Implications:

Phenotype	Cognitive Profile	Demographic/Clinical Features	MRI Correlates
Preserved Cognition (PC)	No impairment	-	-
Mild Single-Domain (MSD)	Mild impairment in one domain	Older, longer disease duration	Higher T2-hyperintense lesion volume (LV)
Mild Multi-Domain (MMD)	Mild impairment in multiple domains	Older, longer disease duration, higher disability	Higher T2 LV, lower thalamic volume
Significant Single-Domain (SSD)	Significant impairment in one domain	Longer disease duration	Lower gray matter cortical volume, thalamic, caudate, putamen, and Accumbens volumes
Significant Multi-Domain (SMD)	Significant impairment in multiple domains	Older, longer disease duration, higher disability, more extensive

 

 Reference:

Damiano Mistri, Tedone N, Biondi D, Vizzino C, Pagani E, Rocca MA, et al. Cognitive phenotypes in multiple sclerosis: mapping the spectrum of impairment. Journal of neurology. 2023 Nov 26;271(4):1571–83.

Cognitive phenotypes in multiple sclerosis: mapping the spectrum of impairment | Journal of Neurology