Researcher finds ‘gold standard’ test for MS wanting

Dr Meaghan Clough researches cognitive speed in early MS

by Anne Crawford

For seven years, researcher Dr Meaghan Clough frequently observed Multiple Sclerosis (MS) patients performing well on the standard test used to measure cognitive function then talk to her about cognitive problems they were facing. She wondered about the discrepancy.

“On further investigation I would realise that actually they did have a cognitive deficit,” Dr Clough said. 

Working memory (WM) and attention deficits are a common – and disturbing – symptom of MS.

Dr Clough decided to investigate the ‘gold standard’ test for processing cognitive speed used to diagnose and measure change in MS patients. The Symbol Digit Modalities Test (SDMT) asks the person to match symbols with numbers from one to nine.

“Recent reviews of the test came out arguing that this is the one-stop measurement used if you wanted to determine if your patient had any sort of cognitive deficits – you give them this and this test and it says ‘yes’ or ‘no’,” Dr Clough said.

A study conducted by researchers in the Ocular Motor Research Laboratory, Department of Neuroscience, led by Dr Clough, found that wasn’t true for working memory deficits in early MS patients.  

The findings were published in The Journal of Clinical Medicine.

Dr Clough gave a cohort of 88 people (63 with early MS and 25 healthy controls) a battery of different tests over five years. These tests targeted four types of WM functions: auditory; visual-spatial; executive (integrating information); and episodic function (retaining information for use in long-term memory). 

“I think one of the biggest issues is that people aren’t really defining what the individual patient has and they’re doing a kind of sledgehammer approach – one size fits all,” she said. “You might have a patient who has auditory working memory issues but you assess them using a visual-spatial working memory test.”

The research was the first and only study to investigate WM phenotypes in early MS, Dr Clough said.

It found that of the early MS cohort more than 60 % were found to have WM impairment. “Working memory and attention deficits have the most devastating impact on a patient’s day-to-day life,” Dr Clough said. “They impact on a wide range of daily tasks such as following instructions or conversations, reading comprehension or organisation and can lead to the patient quitting work or withdrawing socially,” she said. 

The research found visual-spatial working memory was affected most in early MS with patients also often having multiple impairments in other WM functions.

“The next level was – is there one test we can use that gives us really good sensitivity at picking up patients with working memory impairment irrespective of its type so we can give patients one test and are most likely to pick up people with a deficit, no matter what it is?”

Again, the visual-spatial WM test proved the most useful.

A final experiment set out to determine the best test to measure change in the patient’s working memory over time. “What I found was the working memory tests I looked at had ‘practice effect’ – the patients improved with practice.

“We can’t see whether a drug or cognitive rehabilitation is improving anything because we’re just measuring the practice effect.

“The visual-spatial WM test was actually able to show that patients were worsening over time as you might expect.”

Dr Clough said a simple, specific test based on visual-spatial function could be conducted by neurologists to screen for cognitive deficits, and then further investigation using tests for other functions could determine the individual patient’s specific deficit. This would be beneficial clinically and in clinical trials, she said. 

“I think the study is a really important step forward because attention is really on how do we treat or improve these patients’ lives. At the moment we’re trying things that don’t work.”

Dr Clough is currently refining a new test.

Associate Professor Joanne Fielding is the final author on the paper.  

Clough, M; Bartholomew, J; White, OB; Fielding, J. Working Memory Phenotypes in Early Multiple Sclerosis: Appraisal of Phenotype Frequency, Progression and Test Sensitivity. J. Clin. Med. 2022, 11, 2936. https://doi.org/10.3390/jcm11102936