Cognitive problems with FAP linked to thinning of key brain regions
Imaging study finds loss of cortical thickness with disease relative to other adults
Problems with memory and problem-solving in people with hereditary transthyretin amyloidosis (ATTRv), a group of diseases that includes familial amyloid polyneuropathy (FAP), associated with a thinning in specific brain regions, according to a small brain imaging study.
“The reasons for cognitive involvement in ATTRv are still a subject of investigation … [with] indications that cognitive dysfunction may occur in some patients,” the researchers wrote. “Identified brain regions provide potential targets for future investigations.”
The study, “Exploring cognitive functions and brain structure in Hereditary Transthyretin amyloidosis using brain MRI and neuropsychological assessment,” was published in the journal Neurological Sciences.
Cognitive issues reported in some people with familial amyloid polyneuropathy
FAP is a form of ATTRv, a group of conditions marked by the damaging accumulation of toxic clumps of the transthyretin protein in body tissues, due to mutations in the TTR gene.
Those toxic aggregates build mainly in the nerves that branch out from the spinal cord, leading to neurological disease symptoms. These clumps also can accumulate primarily in the heart, and the resulting condition is called ATTRv cardiomyopathy.
While cognitive problems, such as impaired memory, executive function, and other brain issues have been reported in people with ATTRv, their link to the disease remains unclear. Executive function comprises a set of mental skills that helps in planning, problem solving, focusing, and juggling multiple tasks.
No previous study is reported to have used brain imaging to evaluate how changes in the organ’s structure might tie to cognitive problems in patients, the researchers noted.
Scientists in Brazil and Sweden compared cognitive data and MRI measures of the cerebral cortex in 29 ATTRv patients and 26 healthy adults. The cerebral cortex, the brain’s outermost layer, is where information is processed, enabling learning and other complex mental activities.
“While previous studies have suggested that brain atrophy [shrinkage] may occur in ATTRv amyloidosis, our study is the first to use automated and validated tools to explore quantitative brain measures in ATTRv patients,” the researchers wrote. Brain shrinkage indicates the loss of brain cells or of the connections between them.
Patients’ mean age was 43.6, and they had been living with the disease for a median of three years. Over two-thirds (72.4%) carried the V30M mutation, the most common cause of FAP. The remaining patients carried the V122I mutation, one of the most common causes of ATTRv cardiomyopathy.
Healthy adults, as a control group, were matched with patients in terms of age, sex, and years of education.
Cognitive tests support ‘evidence of impairment’ with ATTRv amyloidosis
As expected, patients scored significantly higher than the control group on the World Health Organization Disability Assessment Schedule 2.0, where higher scores indicate worse disability. They also showed significantly higher levels of anxiety.
With cognitive performance, patients scored significantly lower than controls on tests of memory, problem-solving (executive function), visual processing, and language, independent of their levels of anxiety.
While “most patients had a short disease duration,” the researchers wrote, “our results support the existing evidence of cognitive impairment in ATTRv amyloidosis,” and these “may arise early, which [requires] further studies.”
Analysis of the MRI scans available for 20 patients and 23 healthy controls revealed a significant reduction in the overall volume of the cerebral cortex among patients, “although there were no significant correlations with either disease duration or disability,” the researchers wrote.
Patients had significant thinning in the superior temporal sulcus, fusiform gyrus, and temporal gyri — brain regions involved in language, and the processing of visual and auditory information.
Brain regions involved in speech (the pars opercularis, pars orbitalis); decision-making (lateral orbitofrontal cortex); perception, planning, and interpretation of sensory information (inferior parietal cortex); mental imagery and memory (supramarginal gyrus); and gustatory, sensorimotor, and emotion processing (insula) also were significantly thinner among patients than controls.
Thinner brain regions not tied to disease duration in study
Several “significant correlations were observed in relation to cortical thickness,” the team wrote.
For instance, a thinner lateral orbitofrontal cortex, supramarginal gyrus, pars opercularis, and insula each linked with poorer executive function. A thinner inferior temporal gyrus, pars opercularis, and insula significantly linked to worse learning scores.
In addition, the thinner the insula, pars opercularis, and inferior temporal gyrus, the longer the disease duration. However, no link was found between cognitive problems and disease duration, “probably because most patients had a relatively short history of the disease,” the researchers wrote.
“Our investigation revealed a thinner cortical thickness in ATTRv patients compared to controls,” the researchers concluded, adding that “cognition and cortical thickness are affected in other neurodegenerative conditions,” including Alzheimer’s disease.
Larger studies are needed to confirm these findings, the team noted, as well as to understand whether other factors, “such as education level and social environment,” may “contribute to the cognitive outcome.”
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