Interesting findings released from the European Journal of Neurology took a look at differences between men and women with ALS and how they dealt with memory and thinking problems referred to as “cognitive reserves.” The study shows that previous research indicates that about half of people with ALS develop noticeable thinking or behavior problems. It also notes that a person’s education, occupation, and intellectual engagement helped mask the symptoms of cognitive reserve in those patients, making the decline less noticeable. In this new study, researchers also examined differences between the sexes to determine whether cognitive reserve works differently in men and women as both groups experience changes in thinking and memory. The study matched 190 ALS patients (95 males and 95 females) based on age, ALS type (bulbar, spinal, or FTD), disease severity, years of education, and ECAS cognitive scores. (A test known as the Edinburgh Cognitive and Behavioural ALS Screen, an exam that measures thinking and behavioral changes for those with the disease.) (Those who had ALS-causing genetic mutations were not included in the study.)
Men
For men, the results showed that they experienced more brain damage and significantly lower metabolism, even though their test scores were the same as those of others. A brain scan comparison found that men with ALS had lower brain activity (more nerve cell problems) in key thinking areas on both sides of the frontotemporal region that are affected in ALS and Frontotemporal Dementia. The study indicates that men and women scored the same on thinking tests, but men had more hidden brain damage underneath. It also showed that, in men, more years of education were associated with even lower activity in these regions. This is a classic “cognitive reserve masking” pattern, where people with more education can hold off symptoms longer even as more damage builds up. For ALS patients, this suggests that male patients may maintain cognitive function longer, even as their brain condition worsens, meaning their brains are working harder to keep thinking skills normal as the disease progresses. Men compensate by increasing their push on the frontotemporal networks, which are already deteriorating, relying on strengthened connectivity within the frontal lobe rather than redistributing tasks to other regions, and noting that the frontotemporal regions of the brain are where the ALS’s cognitive epicenter takes place.
Women
For women with higher education, they lean on cerebellar and visual-processing regions of the brain to support their thinking. These areas become more active as cognitive reserve increases. Instead of using the same “backup systems” seen in men, women appear to increase activity in areas involved in coordination and certain thinking tasks, as well as in visual–language regions, and to depend on brainstem–cerebellum pathways to help maintain thinking abilities.
To compensate for the changes made by the disease, areas of the brain that control showed increased metabolic activity in regions that include coordination, balance, emotional control, and certain thinking processes, as cognitive reserve increases. Areas like visual processing, memory, and self-reflection are also used to compensate as well.
The study suggests that cognitive reserve is a real thing in ALS. There are differences in what happens in the brains of ALS patients, showing how men and women cope as cognitive reserve takes over, and how the cerebellum plays an active role in working memory, learning, and emotional processing, and acts as a backup system for women. Because men’s brains rely so much of frontaltemporal regions where ALS resides, frontal network overloading may explain why some male ALS patients deteriorate cognitively faster once symptoms begin.
Conclusion
The researchers conclude, “Our study confirms the validity of the CR hypothesis for the cognitive impairment associated with ALS and highlights that sex can contribute to the heterogeneity of reserve mechanisms in this context. We warrant further studies to elucidate the interplay between sex and other demographic, genetic, and social factors, including age, presence of genetic mutations, occupation, and leisure activities, in determining CR in ALS patients. Looking to the long term, the comprehension of the neurobiology underpinning CR could lead to prevention and treatment strategies based on environmental enrichment (EE), and to the development of drugs mimicking the effect of EE (i.e., enviromimetics). In the view of patient-tailored care, the design of these approaches should consider sex-related differences.”
The entire study can be read here in the European Journal of Neurology
