Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue, 2023, Zuppichini et al

[Andy]

Highlights

• Multiple sclerosis (MS) patients experience fatigue and declines in cognitive speed.
• Whole-brain measures of metabolism have been associated with MS symptom severity.
• Prefrontal metabolism was uniquely associated with MS declines in cognitive speed.
• Prefrontal metabolism measures may be sensitive to cognitive speed declines in MS.

Abstract

Background
Most multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients.

Objective
Investigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS.

Methods
MS and healthy control (HC) participants were scanned using a dual-echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue.

Results
MS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group.

Conclusion
Prefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.

Paywall, https://www.msard-journal.com/article/S2211-0348(23)00575-8/fulltext#

 

[SNT Gatchaman]

Often there is the assumption that fatigue in ME is central: neurological or neuropsychiatric. Here a similar assumption is challenged in MS, which I think is important for us - particularly the maladaptive recruitment of networks from the FND world.

Fatigue and cognitive decline are frequently observed in MS disease progression and are associated with decreased vocational ability and quality of life. [...] Despite its prevalence and detrimental impact, the mechanisms underlying MS-related cognitive decline and fatigue remain under investigation and treatments are limited

Fatigue is one of the most common and debilitating symptoms of MS, reported in approximately 83% of patients and associated with reductions in quality of life.

Although the pathophysiology is at present poorly understood, the primary mechanisms proposed to underlie fatigue involve inflammatory processes that lead to structural damage of white and gray matter, and the maladaptive recruitment of networks due to distributed lesions or inflammation

Cerebral metabolic rate of oxygen (CMRO2) is a measure of oxygen utilization that reflects neurometabolic activity and might serve as a biomarker of neuro-inflammation underlying cognitive decline and fatigue

The current study assessed the association between regional task-evoked oxygen metabolic changes and the MS symptoms of cognitive impairment and fatigue.

The results of this study revealed that, after controlling for disease and demographic variables, prefrontal oxygen metabolism changes explained cognitive performance but not fatigue in MS patients.

prefrontal metabolism (or metabolism in any region) did not explain fatigue in either group. Neither did BOLD or CBF in any region. These results suggest that regional measures of metabolism are sensitive to MS-related cognitive changes but not fatigue.

it might be that MS-related fatigue stems from global brain oxygen hypometabolism compared to MS-related cognitive changes that localize to the dorsolateral prefrontal cortex. Furthermore, these results suggest that the MS-related fatigue pathophysiology might be independent of that underlying cognitive decline.

And in relation to normal-appearing white matter (NAWM) —

important to note that prefrontal metabolism was significantly associated with cognitive performance in MS patients after controlling for total lesion volume, suggesting that measures of metabolism might be sensitive to inflammation beyond visible T2-flair lesions

 

[Hutan]

the maladaptive recruitment of networks from the FND world

Sounds like the student presentation session at a COFFI conference...