Healthy habits before symptoms show may slow disease progression
Sociodemographic factors, behavior could factor in how Huntington's develops
A high level of education, low to moderate alcohol intake, not smoking, and controlling one’s weight may slow Huntington’s disease progression among those who’ve yet to have symptoms, a study shows.
“Reducing modifiable risk factors for [Huntington’s] is one way to support the presymptomatic population,” which is made up of people with a Huntington’s-causing mutation, but who don’t yet show overt symptoms, the researchers wrote in the study, “Modifiable factors associated with Huntington’s disease progression in presymptomatic participants,” which was published in the Annals of Clinical and Translational Neurology.
Huntington’s is caused by excessive repeats of the three nucleotides, or DNA building blocks, CAG in the HTT gene, which provides instructions to produce the huntingtin protein. A healthy HTT gene contains 10-35 repeats, but a higher number results in an abnormally long huntingtin protein being produced. This elongated protein is thought to form toxic clumps in the brain, causing damage and triggering the onset of Huntington’s symptoms, including motor, cognitive, and psychiatric problems.
People with 40 CAG repeats or more almost always develop Huntington’s, while those with less than 39 repeats may or may not develop the neurodegenerative disorder. A higher number of CAG repeats is typically associated with a younger age at symptom onset and a faster progression rate. But even among those with a similar CAG repeat number and age at onset, the disease course often differs.
This suggests “an influence of sociodemographic factors, health behaviors, or health history on which intervention might have a positive impact,” wrote researchers in France who sought to identify factors that can be modified to slow Huntington’s disease progression before the first symptoms appear. They chose a presymptomatic population to avoid possible doubts about whether identified factors were the cause or the consequence of the disease.
Assessing Huntington’s disease progression
The study included 2,636 presymptomatic people with more than 35 CAG repeats on the HTT gene who were participating in Enroll-HD (NCT01574053), the world’s largest observational study of Huntington’s. The participants’ mean age was 40 and 57.5% were women. Over a mean follow-up of 3.4 years, all had at least two assessments of disease severity, as measured by the Huntington’s disease rating scale (cUHDRS), where lower scores indicate worse disability.
Based on the mean score difference between the first and last measurement, participants were classified as progressing slower if they had a decline lower than the mean, and progressing faster if their score’s decline had been greater.
The team looked at sex, age, and CAG repeat number as nonmodifiable factors. Modifiable factors at the first assessment included education, alcohol, tobacco, and coffee consumption, and body mass index (BMI), a ratio of height and weight used to estimate body fat. Medical history, and a history of treatments for anxiety and depression also were assessed.
Results showed that faster progressors were significantly more likely to be older, carry more CAG repeats, have a lower level of education, and consume more alcohol relative to slower progressors. Faster progressors also had a significantly higher frequency of simultaneous cardiovascular, metabolic, neurological, and psychiatric disorders, along with a history of treatment for anxiety and depression.
The researchers confirmed that cUHDRS scores declined more rapidly with older age and in presymptomatic participants with more than 42 CAG repeats than in those with fewer than 42 repeats.
Modifiable factors
Regarding modifiable factors, higher education levels, from primary to postsecondary tertiary education, were associated with higher cUHDRS scores, or less disease severity. Higher levels of education, up to a bachelor’s degree or its equivalent, were protective between the ages 35 and 70.
Having a BMI lower than 23.1 kg/m2 (normal range 18.5-24.9) was also linked with better cUHDRS scores before age 40, but after that, a BMI above 27 kg/m2 was found to be more protective than lower BMIs.
Not smoking and consuming low to moderate amounts of alcohol (up to 15 units a week) were associated with higher cUHDRS scores relative to smoking and no alcohol consumption, respectively. A unit of alcohol is defined as 10 mL, or 8 grams, of pure alcohol, with a standard beer containing 1.7 units, a standard glass of wine having 2.1 units, and 1 unit in a single shot of spirits.
Beyond 15 alcohol units a week, cUHDRS scores tended to worsen or stabilize. Given that only 5.3% of participants reported such high level of consumption, “which seems rather low,” the findings “concerning the effects of alcohol consumption should be taken with caution,” the researchers said.
Being a woman and having no history of antidepressant use were also linked to slower disease progression. Frequent coffee consumption showed a moderately protective effect.
“Education, low to moderate alcohol consumption, [recurrent] coffee consumption, and nonsmoking may be protective factors against disease progression before onset,” the researchers wrote, adding that a BMI below 23 kg/m2 may be protective before age 40. “Multi-domain management of above risk factors could be an efficient prevention strategy to delay the onset and slow the progression of HD since the presymptomatic phase.”
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