Core Symptoms of Adult-onset DM1: Cognitive Problems, Apathy, Fatigue

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

An illustration of a person's head, highlighting the brain.

Brain abnormalities in people with adult-onset myotonic dystrophy type 1 (DM1) are significantly associated with cognitive impairment, apathy, and daytime sleepiness, a study shows.

Notably, no such link was found for depression and anxiety, suggesting that these commonly reported symptoms are instead secondary manifestations of living and coping with this chronic disease.

Findings suggest that cognitive difficulties, apathy, and daytime sleepiness are the core brain-related symptoms of adult-onset DM1, and may help to identify and develop better therapeutic targets, biomarkers, and clinical trial measures, the researchers noted.

The study, “Cognitive Deficits, Apathy, and Hypersomnolence Represent the Core Brain Symptoms of Adult-Onset Myotonic Dystrophy Type 1,” was published in the journal Frontiers in Neurology.

Recommended Reading

Avidity Secures $100M Funding to Advance Treatments for Myotonic Dystrophy, DMD

DM1, the most common form of muscular dystrophy in adults, is a progressive disease caused by an abnormal expansion of a specific DNA sequence in the DMPK gene. While its hallmark features include muscle weakness, wasting, and stiffness, “some of the most disabling symptoms of the disease are cognitive and behavioral,” the researchers wrote.

People with DM1 often show cognitive impairment, apathy (lack of motivation and overall indifference), daytime sleepiness or fatigue, depression, and anxiety, which can have a significant burden on both patients and their caregivers.

These non-motor symptoms are thought to be directly related to DM1-associated brain abnormalities, including lesions in white matter, the part of the brain made of nerve cell fibers.

With advances in potential treatments, including those administered directly into the brain, “it is crucial to distinguish what features of DM1 are truly related to brain [abnormalities] and which features may be secondary manifestations of living with a chronic neurologic disease,” the researchers wrote.

A research team in the U.S. and the U.K. evaluated associations between white matter lesions, and cognitive and behavioral symptoms in adult-onset DM1 patients, as well as whether brain damage or these symptoms worsened with disease duration.

These analyses were part of a larger study, called the Iowa DM1 Brain study, which is evaluating common symptoms and brain changes in adult-onset DM1 patients and in people at risk for DM1 (due to a family history of the disease) over time.

This study included 39 adult-onset DM1 patients (27 women and 12 men) and 71 healthy adults (46 women and 25 men), including patients’ spouses, serving as controls. Patients had a mean age of 45.5, and had lived with the disease for a mean of 12.9 years (range, 2.4–28.9 years). No significant differences in sex or age existed between the groups.

Participants underwent brain imaging to measure white matter lesions, and completed validated tests, scales, and questionnaires of cognitive function, depression, anxiety, apathy, and daytime sleepiness. As patients often under-rate apathy, 24 of them had a person familiar with them complete an “informant version” of the apathy scale.

DM1 patients had significantly more brain abnormalities, cognitive impairment, depression, anxiety, apathy, and daytime sleepiness than controls, results showed.

Those with DM1 and greater cognitive impairment also had significantly more depression and anxiety, but not more daytime sleepiness or apathy (neither self-reported nor informant-reported).

This suggested that cognitive deficits may increase anxiety and depression symptoms in people with a chronic disease, as DM1 patients with such deficits may be using “more emotion-focused coping strategies instead of problem-focused coping strategies,” the researchers wrote.

Notably, greater white matter damage was significantly associated with more cognitive deficits, apathy, and daytime sleepiness. However, when adjusted for cognitive abilities, no significant links were found between brain abnormalities and anxiety or depression.

These findings suggested that cognitive impairment, apathy, and daytime sleepiness were the core brain-related symptoms of adult-onset DM1.

In agreement, patients with longer disease duration, used as a marker of disease progression, showed significantly more white matter abnormalities, daytime sleepiness, and apathy, but not depression or anxiety.

While the analysis found no significant link for cognitive ability, previous studies highlighted a significant association between DM1 progression and cognitive impairment.

These data “support the hypothesis that cognitive deficits, hypersomnolence [daytime sleepiness], and apathy are due to the underlying [neurological mechanisms] of myotonic dystrophy type 1, as measured by cerebral white matter [abnormalities] and disease duration,” the researchers wrote.

“Increased symptoms of depression and anxiety are secondary to a combination of the physical symptoms of having a neuromuscular disorder and the emotional stress of coping with a chronic and debilitating disorder,” they added.

These findings “contribute to a better understanding of disease [brain mechanisms] and represent important therapeutic targets for clinical trials,” the team wrote.

They also noted that longer-term data from the Iowa DM1 Brain study will allow progression of these brain-related symptoms to be evaluated over time, and that one- and two-year analyses are currently underway.

“Whether progression in these symptoms occur[s] rapidly is important to assess in the context of whether or not they may represent appropriate end-points [measures] for clinical trials,” the researchers wrote.