Objective Cognitive Impairment Linked to Sex, Stroke, and IQ, Study Shows

Male sex, history of stroke, and intelligence quotient (IQ) are associated with an increased risk of objective cognitive impairment in Fabry disease patients. Depressive symptoms, on the other hand, are related to increased subjective cognitive complaints, a study found.

The study, “Predictors of objective cognitive impairment and subjective cognitive complaints in patients with Fabry disease,” was published in Scientific Reports.

During routine clinic visits, Fabry disease patients often mention subjective cognitive impairment —self-made observations about the ability to think and experience. Recent research shows that these subjective cognitive impairments are often related to depressive symptoms and not to impairments diagnosed by clinicians — objective cognitive impairments.

On the contrary, white matter lesions, stroke, and depression are known to result in objective cognitive impairment in the general population.

Sex and disease presentation — phenotype — are known important predictors of Fabry’s disease course, but how they relate to objective cognitive impairments is not clear for a number of reasons.

Understanding the relationship between subjective cognitive complaints, depressive symptoms, and objective cognitive impairment can have significant implications for the therapeutic measures indicated to address such complaints.

For these reasons, researchers from the Academic Medical Center at the University of Amsterdam investigated the prevalence of objective cognitive impairment, subjective cognitive complaints, and depressive symptoms. They used this information to then explore their risk factors and how they link to Fabry participants as a group as well as subgroups defined by sex and Fabry phenotype (i.e. classical or non-classical).

The researchers assessed cognitive functioning using a neuropsychological test battery and subjective cognitive complaints using a structured interview. They measured depressive symptoms using a depression scale (CESD). Eighty-one patients were included with an average age of 44.5 years, mostly women, and presenting with classical Fabry disease.

“We included 81 patients, more than half of the known patients in the Netherlands, a fairly large group for a rare disease like Fabry disease,” the researchers said. “This study is the first to combine data on subjective cognitive complaints, depressive symptoms, cognitive functioning, and MRI brain parameters in subgroups of patients divided by sex and Fabry disease phenotype.”

In general, more than half of the participants experienced subjective cognitive complaints, but this was no different for subgroups split by sex and phenotype. On the other hand, objective cognitive impairment was present in 13 patients (16%) and predominantly in men with classical Fabry (41%) and mostly affected executive function — the cognitive processes controlling behavior.

Objective cognitive impairment was also found in a significant number of men with non-classical Fabry (27%) but to a lesser proportion. Conversely, the prevalence of objective cognitive impairment was markedly lower in women with classical Fabry disease (7%) and was absent in women with non-classical Fabry.

When looking at variables affecting objective cognitive impairment, male sex was positively related and higher premorbid IQ (an estimate of a person’s intellectual functioning before onset of brain dysfunction) was negatively related to the presence of objective cognitive impairment.

Also, there was a positive relation between brain parameters and history of stroke with the presence of objective cognitive impairment. There was no relation between objective cognitive impairment and depressive symptoms.

On the contrary, subjective cognitive complaints were not related to objective cognitive impairment but showed a clear relation with both depression in the past and current depressive symptoms.

“In this large sample of Dutch patients with Fabry disease we have, for the first time, shown a relationship between sex, phenotype, and risk for objective cognitive impairment,” the researchers said.

“Evaluation of subjective cognitive complaints in patients with Fabry disease should, therefore, include a psychological evaluation and healthcare professionals should focus on recognition and treatment of depressive symptoms,” they added.