Late-onset MG Tied to Poor Memory, Brain Shrinkage in Small Study

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Men with late-onset myasthenia gravis (MG) show poorer memory and spatial orientation, as well as lower-than-normal volumes of brain regions involved in such functions, than their healthy peers, according to a small single-center study in Germany.

These findings add to a number of studies reporting cognitive deficits in MG patients, and point to brain shrinkage as a potential cause of such deficits.

However, larger studies are needed to confirm these findings and the underlying mechanisms of memory and spatial orientation deficits in people with MG, the researchers noted.

The study, “Structural and functional brain alterations in patients with myasthenia gravis,” was published in the journal Brain Communications.

MG is an autoimmune disease caused by the abnormal production of self-reactive antibodies against proteins, such as the acetylcholine receptor, that play a key role in the function of the neuromuscular junction (NMJ). The NMJ is the point of contact between nerve cells and the muscles they control, and where nerve-muscle communication takes place. Having fewer acetylcholine receptors available breaks down such communication, and leads to the disorder’s hallmark symptoms of muscle weakness and fatigue.

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Symptoms of MG can develop at any age, including during childhood, but the disorder most commonly affects women younger than 40, and men older than 60 — in which case it is called late-onset MG.

While some previous studies have described cognitive deficits — “especially affecting verbal and visual learning, processing speed, reaction time and memory” — in MG patients, the researchers wrote, others “reported no significant differences” relative to healthy people.

In addition, whether this potential cognitive dysfunction is related to structural changes in the brain, namely shrinkage, or atrophy, of specific brain regions, remains largely unclear.

“Understanding potential brain alterations in MG can enhance our knowledge of the [disease-associated] mechanisms of MG and help to develop tailored interventions to counteract cognitive deficits,” the researchers wrote.

To learn more, a team of researchers in Germany evaluated the cognitive function and gray matter volume of 11 men with mild to moderate, late-onset MG, and 11 age-, sex-, and education-matched healthy men, who served as controls.

In the brain, gray matter — so named for its pinkish-gray color — is mainly made of nerve cell bodies, while white matter is made of nerve fibers. In late-onset MG, or LOMG, disease symptoms usually arise in patients ages 45–70.

The patients in this study, followed at a single German neurology clinic, were diagnosed between 2001 and 2017 and their disease duration ranged from 10 months to more than 16 years.

Most were receiving immunosuppressive treatment and/or anticholinesterases, specifically pyridostigmine (sold as Mestinon, among other brand names). None showed signs of dementia or depression.

All participants underwent a battery of cognitive and spatial orientation tests, as well as MRI scans to assess gray matter volume. The blood levels of brain-derived neurotrophic factor (BDNF) — a molecule involved in NMJ function that also promotes nerve cell survival and growth — also were measured.

Results showed that men with LOMG had significant deficits in terms of verbal memory, visuospatial working memory, and non-visual somatosensory-related spatial orientation relative to matched controls.

Visuospatial working memory is the capacity to maintain a representation of visuospatial information for a brief period. Somatosensory-related spatial orientation is based on the somatosensory system, a network of nerves responsible for the perception of temperature, touch, pain, movement, and body position in space.

There were no group differences in long-term memory, visual-verbal performance, word fluency, and vestibular-related spatial orientation, which is based on head-in-space position and movement due to signals from the inner ear.

Compared with controls, LOMG patients also showed significantly lower gray matter volumes in three brain regions: the left cingulate gyrus, the left inferior parietal lobule, and the left fusiform gyrus.

Notably, the cingulate gyrus plays a role in spatial memory and is involved in sensorimotor functions, while the inferior parietal lobule has a role in the processing of somatosensory information, spatial awareness, and working memory. The fusiform gyrus is involved in multisensory object perception and tactile recognition.

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Given that there were no significant differences between groups in terms of dementia, depression, and fatigue, which could influence brain function, these findings suggest that LOMG is associated with cognitive and spatial orientation deficits, at least in male patients.

These deficits may be related to brain shrinkage — in the cingulate gyrus and the inferior parietal lobule — which are involved in such functions.

While no significant associations were found between gray matter volume in these regions and cognitive and spatial orientation performance, this may be due to the small number of participants in this study, the team noted.

Moreover, men with late-onset MG showed significantly higher levels of BDNF in the blood as compared with matched, healthy men, which may reflect a protective mechanism against the progressive loss of NMJs.

These results suggest that MG “is associated with structural and functional brain alterations,” the researchers wrote, adding that “future research is needed to replicate these findings … in a larger sample and to investigate the underlying mechanisms in more detail.”

Further studies should also look at both male and female patients and follow them over time.

“Based on these preliminary results indicating structural and functional brain changes in MG, future studies could investigate the potential impact of physical exercise interventions to counteract these changes,” the team concluded.