Multiple sclerosis

Cognitive impairment affects 40-65% of people with MS. Why? In the past year, a number of studies have helped us build a better picture of the precise nature of cognitive problems that may affect multiple sclerosis sufferers:

  • poorer performance on executive function tasks is fully explained by slower processing speed (which is presumably a function of the degradation in white matter characteristic of MS)
  • slowing in processing speed is associated with weaker connections between the executive area and the brain regions involved in carrying out cognitive tasks
  • cognitive reserve helps counter the decline in memory and cognitive efficiency
  • brain reserve (greater brain volume, ie less shrinkage) helps counter the decline in cognitive efficiency
  • working memory capacity explains the link between cognitive reserve and long-term memory
  • subjective cognitive fatigue is linked to the time spent on the task, not on its difficulty
  • mnemonic training helps protect against cognitive decline, but appears to be less helpful in those with slow processing speed.

What all this implies is that a multi-pronged approach is called for, involving:

  • working memory training
  • training in effective memory strategies
  • practice in breaking down cognitive tasks into more manageable chunks of time
  • practice in framing tasks to accommodate slower processing speed
  • physical and mental activities that encourage neurogenesis (growing more neurons) and synaptogenesis (growing more connections).

Here's some more detail on those studies:

Slow processing speed accounts for executive deficits in MS

A study of 50 patients with MS and 28 healthy controls found no differences in performance on executive function tasks when differences in processing speed were controlled for. In other words, although MS patients performed more poorly than controls on these tasks, the difference was fully accounted for by the differences in processing speed. There were no differences in performance when there was no processing speed component to the task. Similarly, MS patients with a greater degree of brain atrophy performed more poorly than those with less atrophy, but again, this only occurred when there was a processing speed aspect to the task, and was fully accounted for by processing speed differences.

[3939] Leavitt, V. M., Wylie G., Krch D., Chiaravalloti N. D., DeLuca J., & Sumowski J. F.
(2014).  Does slowed processing speed account for executive deficits in multiple sclerosis? Evidence from neuropsychological performance and structural neuroimaging..
Rehabilitation Psychology. 59(4), 422 - 428.

Functional connectivity factor in cognitive decline in MS

A brain imaging study involving 29 participants with relapsing-remitting MS and 23 age- and sex- matched healthy controls found that, as expected, those with MS were much slower on a processing speed task, although they were as accurate as the controls. This slowing was associated with weaker functional connections between the dorsolateral prefrontal cortex (the executive area) and the regions responsible for carrying out the task. It's thought that this is probably due to decreased white matter (white matter degradation is symptomatic of MS).

[3938] Hubbard, N. A., Hutchison J. L., Turner M. P., Sundaram S., Oasay L., Robinson D., et al.
(2015).  Asynchrony in Executive Networks Predicts Cognitive Slowing in Multiple Sclerosis.

Brain and cognitive reserve protect against cognitive decline in MS

A study compared memory, cognitive efficiency, vocabulary, and brain volume in 40 patients with MS, at baseline and 4.5 years later. After controlling for disease progression, they found that those with better vocabulary (a proxy for cognitive reserve) experienced less decline in memory and cognitive efficiency, and those with less brain atrophy over the period showed less decline in cognitive efficiency.

Cognitive efficiency is a somewhat fuzzy concept, but essentially has to do with how much time and effort you need to acquire new knowledge; in this study, it was assessed using the Symbol Digit Modalities Test and Paced Auditory Serial Addition Task, two tests commonly used to detect cognitive impairment in MS patients.

[3943] Sumowski, J. F., Rocca M. A., Leavitt V. M., Dackovic J., Mesaros S., Drulovic J., et al.
(2014).  Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS.
Neurology. 82(20), 1776 - 1783.

Working memory capacity accounts for link between cognitive reserve & better memory

A study involving 70 patients with MS has found that working memory capacity explained the relationship between cognitive reserve and long-term memory, suggesting that interventions targeted at working memory may help protect against decline in long-term memory.

[3941] Sandry, J., & Sumowski J. F.
(2014).  Working Memory Mediates the Relationship between Intellectual Enrichment and Long-Term Memory in Multiple Sclerosis: An Exploratory Analysis of Cognitive Reserve.
Journal of the International Neuropsychological Society. 20(08), 868 - 872.

Cognitive fatigue linked to time on task, not difficulty

A study investigating cognitive fatigue in 32 individuals with MS and 24 controls has found that subjective and objective fatigue were independent of one another, and that subjective cognitive fatigue increased as time on task increased. This increase in cognitive fatigue was greater in the MS group. No relationship was found between cognitive fatigue and cognitive load. Fatigue was greater for the processing speed task than the working memory task.

In other words, the length of time spent is far more important than the difficulty of the task.

[3940] Sandry, J., Genova H. M., Dobryakova E., DeLuca J., & Wylie G.
(2014).  Subjective cognitive fatigue in multiple sclerosis depends on task length.
Frontiers in Neurology. 5, 214.

Story mnemonic training helps some

A series of small studies have found cognitive benefits for MS patients from a 10-session training program designed to build their memory skills using a modified story mnemonic. The MEMREHAB Trial involved 85 patients with MS, of whom 45 received the training. In the most recent analyses of the data, the benefits were found to be maintained six months later, but unfortunately, it appears that those with processing speed deficits gain less benefit from the training.

The training consists of four 45-minute sessions focused on building imagery skills, in which participants were given a story with highly visualizable scenes and given facilitated practice in using visualization to help them remember the story. In the next four sessions, they were given lists of words and instructed in how to build a memorable story from these words, that they could visualize. The sessions employed increasingly unrelated word lists. In the final two sessions, participants were taught how to apply the technique in real-world situations.

[3936] Chiaravalloti, N. D., & DeLuca J.
(2015).  The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: A sub-analysis of the MEMREHAB trial.
Multiple Sclerosis (Houndmills, Basingstoke, England).

[3937] Dobryakova, E., Wylie G. R., DeLuca J., & Chiaravalloti N. D.
(2014).  A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.
Brain Imaging and Behavior. 8(3), 403 - 406.

Cognitive decline is common in those with multiple sclerosis, but not everyone is so afflicted. What governs whether an individual will suffer cognitive impairment? One proposed factor is cognitive reserve, and a new study adds to the evidence that cognitive reserve does indeed help protect against cognitive decline, as it does with age-related decline.

The study involved 50 people with multiple sclerosis plus a control group included 157 clinically healthy adults of similar age and education level, and found that those with more education (defined as more than 13 years of schooling) were protected against cognitive impairment. This is not simply a matter of the more educated starting off from a higher base! MS patients with low education performed more poorly on a demanding cognitive test than healthy controls with the same level of education, while MS patients with high education performed at the same level as their matched controls.

On the other hand, occupation (also implicated as a factor in cognitive reserve, though a less important one than education) did not have an effect. Nor did fatigue.

Cognitive performance was evaluated using the Paced Auditory Serial Addition Test (PASAT), in which a series of single digit numbers are presented and the two most recent digits must be summed. This test has high sensitivity in detecting MS-related cognitive deficits as it relies strongly on working memory and information processing speed abilities. The poorer performance of low-education MS patients was only found at higher speeds.

[3474] Scarpazza, C., Braghittoni D., Casale B., Malagú S., Mattioli F., di Pellegrino G., et al.
(2013).  Education protects against cognitive changes associated with multiple sclerosis.
Restorative Neurology and Neuroscience. 31(5), 619 - 631.

A study involving 187 children and adolescents with multiple sclerosis, plus 44 who experienced their first neurologic episode (clinically isolated syndrome) indicative of MS, has found that 35% of those with MS and 18% of those with clinically isolated syndrome were cognitively impaired. Cognitive assessment was done using a battery of 11 tests. The most common areas of impairment were fine motor coordination, visual-motor integration, and speeded information processing.

[3319] Julian, L., Serafin D., Charvet L., Ackerson J., Benedict R., Braaten E., et al.
(2013).  Cognitive Impairment Occurs in Children and Adolescents With Multiple Sclerosis Results From a United States Network.
Journal of Child Neurology. 28(1), 102 - 107.

Problems with myelin — demyelination (seen most dramatically in MS, but also in other forms of neurodegeneration, including normal aging and depression); failure to develop sufficient myelin (in children and adolescents) — are increasingly being implicated in a wide range of disorders. A new animal study adds to that evidence by showing that social isolation brings about both depression and loss of myelin.

In the study, adult mice were isolated for eight weeks (which is of course longer for a mouse than it is to us) to induce a depressive-like state. They were then introduced to a mouse they hadn’t seen before. Although typically very social animals, those who had been socially isolated didn’t show any interest in interacting with the new mouse — a common pattern in human behavior as well.

Analysis of their brains revealed significantly lower levels of gene transcription for oligodendrocyte cells (the components of myelin) in the prefrontal cortex. This appeared to be caused by a lower production of heterochromatin (tightly packed DNA) in the cell nuclei, producing less mature oligodendrocytes.

Interestingly, even short periods of isolation were sufficient to produce changes in chromatin and myelin, although behavior wasn’t affected.

Happily, however, regardless of length of isolation, myelin production went back to normal after a period of social integration.

The findings add to the evidence that environmental factors can have significant effects on brain development and function, and support the idea that socializing is good for the brain.

It’s estimated that 43%-70% of those with multiple sclerosis suffer from some level of cognitive impairment (yes, a very broad range! perhaps the finding of this study offers one clue why). Most commonly, this is seen in slower processing speed, impaired memory, impaired executive function, and poorer visuospatial processing. There are a number of factors that have been implicated in why some people suffer from cognitive impairment and others don’t, such as age of onset and male gender. As with dementia, depression also may be a factor, while cognitive reserve appears protective.

Another factor specific to MS may be temperature. Previous research has shown that people with MS tend to have more symptoms and greater lesion activity when the weather is warmer. More recently, this association has also been found with memory and processing speed.

I mentioned this research very briefly last year, when it was presented at conference. Here are a few more details now the journal article is out.

There were two parts to this study: cross-sectional and longitudinal. In the former, 40 patients with MS and 40 healthy controls were recruited throughout the calendar year, and cognitive performance and outdoor temperature were recorded for the day of testing. A different group of 45 patients with MS were recruited for the longitudinal analysis, in which cognitive status and outdoor temperature were recorded twice, six months apart.

In the cross-sectional analysis, warmer temperature was related to significantly worse cognitive performance in patients with MS, while controls were unaffected by temperature. Similarly, the longitudinal analysis found that an increased outdoor temperature from the first cognitive test to the second was related to a decline in cognitive performance within patients with MS.

A study involving 50 people with MS (aged 18-65), of whom half used marijuana for pain relief, has found that marijuana users performed significantly worse on tests of attention, speed of thinking, executive function and visual perception of spatial relationships between objects. Those who used marijuana were also twice as likely as non-users to be classified as globally cognitively impaired.

The two groups were matched for age, gender, level of education, IQ before diagnosis, level of disability and duration of time with MS. On average, the duration of marijuana use was 26 years, and 72% reported smoking marijuana on a daily basis while 24% reported weekly use and one person reported bi-weekly use. There were no differences between the groups on measures of depression and anxiety.

And on a less-expected note, a study involving 40 people with multiple sclerosis and 40 people without MS has found those with MS scored 70% better on cognitive tests during cooler days compared to warmer days of the year. There was no link between test scores and temperature for those without MS.

[2178] Honarmand, K., Tierney M. C., O'Connor P., & Feinstein A.
(2011).  Effects of cannabis on cognitive function in patients with multiple sclerosis.
Neurology. 76(13), 1153 - 1160.

The findings of the temperature study were presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

Memory and learning problems often occur in multiple sclerosis, but bewilderingly, are only weakly associated with the severity of the disease. A study involving 44 people around the age of 45 who had MS for an average of 11 years has found that those with a mentally active lifestyle had good scores on the tests of learning and memory even if they had higher amounts of brain damage. The findings suggest that, as with Alzheimer’s disease, 'cognitive reserve' protects against cognitive impairment. Differences in cognitive reserve may explain why some people have memory problems early in the disease, while others do not develop memory problems until much later, if at all.

A study involving 236 persons with multiple sclerosis has found that only 7% of those with secondary-progressive MS showed sufficient vitamin D in their blood, compared to 18.3% of patients with the less severe relapsing-remitting type, and that higher levels of vitamin D3 and its byproducts were associated with better scores on cognitive tests (especially reasoning and planning), and less brain atrophy and fewer brain lesions. Lower-than-normal vitamin D status is known to be associated with a higher risk of developing MS

The results were reported at the American Academy of Neurology's 62nd Annual Meeting in Toronto, April 10–17, 2010.

Older news items (pre-2010) brought over from the old website

MS can affect children's IQ, thinking skills

Multiple sclerosis typically starts in young adulthood, but about 5% start in childhood or adolescence. A study of 63 children under age 18 with MS has found that they more likely to have low IQ scores than healthy controls. Five of the children with MS had IQ scores of less than 70 (none of the controls did), 15 had IQ scores between 70 and 89 (compared to two of the controls), and 31% of the MS children met the criteria for cognitive impairment compared to less than 5% of the controls. Low IQs were correlated with younger age at onset. About 30% of the children with MS also had language difficulties, which is not common in adults with MS. It may be that children are particularly vulnerable to the effects of MS because their brain is still developing.

[1261] Lopez, M., Patti F., Vecchio R., Pozzilli C., Bianchi V., Roscio M., et al.
(2008).  Cognitive and psychosocial features of childhood and juvenile MS.
Neurology. 70(20), 1891 - 1897.

Smoking marijuana impairs cognitive function in MS patients

A study of 140 Canadians with multiple sclerosis has found that those (10) who were defined as current marijuana users performed 50% slower on tests of information processing speed compared to matched MS patients who did not smoke marijuana. There was also a significant association between smoking marijuana and emotional problems such as depression and anxiety.

[1339] Ghaffar, O., & Feinstein A.
(2008).  Multiple sclerosis and cannabis. A cognitive and psychiatric study.
Neurology. 01.wnl.0000304046.23960.25 - 01.wnl.0000304046.23960.25.

Preconditioning could prevent injury to dendrites in neurological diseases

New research has revealed a previously unknown mechanism by which brain cells can be damaged during chronic neurodegenerative diseases such as Alzheimer's, multiple sclerosis, Parkinson's and dementia associated with HIV. When inflammation occurs in the brain, nerve impulses can become toxic. Instead of triggering the formation of memories, these impulses can inflict injury on neurons and disrupt neural function. Understanding this mechanism could provide a new path for drugs to treat the diseases, perhaps by chemical preconditioning to induce adaptations in nerve cells that would enable the cells to better withstand toxic attacks, prevent injury, and preserve function.

[760] Bellizzi, M. J.
(2005).  Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of platelet-activating factor.
Journal of Clinical Investigation. 115(11), 3185 - 3192.

Ginkgo may improve executive function in MS patients

A study of 39 MS patients found that those receiving ginkgo biloba were about 13% faster on a Stroop test (measures a person's ability to pay attention and to sort conflicting information). Such a difference would be comparable to differences in scores between healthy people ages 30 to 39 and those ages 50 to 59. The benefit appeared to be greatest for those who had certain problems with the Stroop test.

The study was presented at the American Academy of Neurology's 57th Annual Meeting in Miami Beach, Fla.

Alzheimer's drug improves cognition in MS patients

An estimated 50% of multiple sclerosis patients suffer some degree of cognitive impairment. A pilot study suggests that donepezil, a drug widely used for treating dementia in Alzheimer's patients, may improve memory and cognition in MS patients who are mild to moderately cognitively impaired. The trial involved 69 MS patients. Over 65% of those given donepezil showed cognitive improvement, compared to 32% of those receiving a placebo.

The study was presented by Laura Krupp at the American Academy of Neurology 56th Annual Meeting in San Francisco, Calif., on April 27.

Ginkgo biloba may slow cognitive decline in patients with mild multiple sclerosis

A six-month double-blind, placebo-controlled pilot study of 23 individuals with mild multiple sclerosis found that patients who took the herb Ginkgo biloba performed better on neuropsychological tests compared to those who took the inactive placebo.

Corey-Bloom, J., Kenney, C. & Norman, M. 2002. Paper presented at the annual meeting of the American Academy of Neurology on April 18 in Denver, Colorado.

Alzheimer's drug may help cognitive impairment in patients with multiple sclerosis

Cognitive problems affect up to 60% of patients with multiple sclerosis. Treatment of MS has until now paid little attention to this aspect of the disease. A preliminary study of 17 patients with advanced MS and severe cognitive impairment found that a drug currently used to treat mild to moderate dementia from Alzheimer’s disease was noticeably effective in improving the cognitive functioning in many of the MS patients. A study of 240 patients at 21 hospitals and medical centers is now about to commence.

Driving problems for those with Multiple Sclerosis

People who suffer from cognitive difficulties related to Multiple Sclerosis (MS) may have a slower driving reaction time and increased risk of accidents. The study compared 13 people with MS who exhibited cognitive difficulties, 15 people with MS who did not exhibit cognitive difficulties, and 17 people without MS. Based on two computerized driving tests, those with MS who exhibited cognitive difficulties had a slower response time by 1,721 milliseconds than the other MS participants. In addition, 29 percent of these people tested as high risk for accident involvement.

[2573] Schultheis, M. T., Garay E., & DeLuca J.
(2001).  The influence of cognitive impairment on driving performance in multiple sclerosis.
Neurology. 56(8), 1089 - 1094.