Cognitive resilience — the absence of dementia despite extensive amyloid and tau pathology — was linked to the myocyte enhancer factor 2 (MEF2) gene family, researchers reported.
In two datasets totaling about 1,000 people, cognitive resilience was highly correlated with expression of MEF2 and many of the genes it regulates, according to Li-Huei Tsai, PhD, of Massachusetts Institute of Technology in Cambridge, and colleagues.
MEF2 also was more active in the brains of mice exposed to a cognitively stimulating environment, they reported in Science Translational Medicine. These mice performed better in learning and memory tasks.
The findings shed light on “the well-described phenomenon of cognitive resilience,” Tsai told MedPage Today.
The strongest epidemiological predictors of cognitive resilience are mentally stimulating activities including high education levels and cognitively demanding occupations. More recent research has shown that people who engage in cognitively stimulating activities have a lower risk of age-related memory loss. Some centenarians have shown high cognitive performance despite varying loads of amyloid beta, neurofibrillary tangles, and neuritic plaques.
This new research suggests a previously unappreciated role for MEF2 transcription factors and their potential as biomarkers or therapeutic targets, Tsai noted.
