Approximately one-third of Fabry disease patients have cognitive impairments, a feature more common in those who have a deficient blood supply to the brain (called cerebrovascular disease), according to researchers in Denmark.
Their study, “Cognitive Impairments and Subjective Cognitive Complaints in Fabry Disease: A Nationwide Study and Review of the Literature,” was published in JIMD Reports.
“This article provides important insight regarding the frequency and nature of cognitive impairments in a large cohort of patients with Fabry disease,” researchers wrote.
Fabry disease is caused by mutations affecting the GLA gene that lead to the accumulation of glycosphingolipids in cells. A buildup of these fatty molecules can affect several tissues in the body, promoting nerve-cell damage and associated pain, renal disease, and cardiovascular and gastrointestinal dysfunction.
Previous studies have suggested that Fabry disease could be linked to cognitive impairment. Reduced blood flow to the brain and the consequent development of brain lesions are believed to be the main cause for cognitive deficits in this population.
Slower psychomotor response (movement or muscular activity associated with mental processes), reduced attention, and executive functions are some of the cognitive manifestations reported. But the prevalence of these symptoms in Fabry patients is still unclear.
Researchers at Denmark’s University of Copenhagen evaluated the cognitive performance and complaints of 41 patients with confirmed Fabry disease. The participants underwent cognitive testing that measured their responses in 13 different domains, including motor response, memory, and verbal fluency.
The results revealed that 29.3% of the participants were cognitively impaired, as determined by low scores in at least four different tests.
Tests with more frequent lower scores were the Stroop test, the Symbol Digit Modalities Test (SDMT), and the Trail Making Test B, which evaluates processing speed and motor function. In general, all patients retained normal memory ability, with test scores within normal range.
Gender, disease severity scores, enzyme activity, depression status, or duration of the disease were found to have no impact on the development of cognitive deficits.
“Thus, cognitive impairment in Fabry disease does not seem to occur solely by having symptoms for many years or by having high disease burden,” researchers wrote.
In comparison, five of the seven patients who had brain lesions or a clinical history consistent with cerebrovascular disease were found to have cognitive deficits. This suggests that “history of identifiable cerebrovascular lesions is significantly associated with classification of cognitive impairment,” researchers wrote.
When questioned about their perception of their own cognitive status, only three patients reported subjective cognitive complaints. However, lower scores in the Perceived Deficits Questionnaire — a screening method that measures the degree to which individuals perceive themselves as experiencing cognitive difficulties — were found to be associated with the depressive status of the patients.
“In general, subjective cognitive complaints were not frequent in this patient group, and subjective perceptions of cognition were not associated with cognitive performances,” researchers wrote.
Similar to previous results, this study shows that Fabry patients have cognitive impairments, most commonly affecting psychomotor speed, attention, and executive functions.
“Thus, cognitive testing seems important when pursuing suspicion of cognitive deficits in patients with Fabry disease,” authors concluded.