Dependence of cognitive ability on synchronous neural interactions determined by magnetoencephalography.

Previous studies have shown that synchronous neural interactions (SNIs) underlying healthy brain function can be readily distinguished from neural anomalies associated with diseases including dementia; however, it is imperative to identify biomarkers that facilitate early identification of individuals at risk for cognitive decline before the onset of clinical symptoms. Here, we evaluated whether variation in brain function, controlling for age, corresponds with subtle decrements in cognitive performance in cognitively healthy women. A total of 251 women (age range 24-102 yr) who performed above established cutoffs on the Montreal cognitive assessment (MoCA) also underwent a task-free magnetoencephalography scan from which SNIs were computed. The results demonstrated that increased SNI was significantly associated with decreased cognitive performance (r2 = 0.923, P = 0.009), controlling for age. Compared with the lowest performers with normal cognition (MoCA = 26), SNI of the highest performers (MoCA = 30) was associated with decorrelation primarily in the right anterior temporal cortex region, with additional (weaker) foci in left anterior temporal cortex, right posterior temporal cortex, and cerebellum. The findings highlight the relevance of neural network decorrelation on cognitive functioning and suggest that subtle increases in SNI may presage future cognitive impairment.NEW & NOTEWORTHY This study in cognitively healthy women showed that decreased cognitive performance is associated with increased neural network correlations, particularly involving the temporal cortices. As healthy brain function relies on dynamic neural network communication, these findings suggest that subtle increases in correlated neural network activity may be a useful early indicator of decrements in cognitive function.

The effects of human leukocyte antigen DRB1*13 and apolipoprotein E on age-related variability of synchronous neural interactions in healthy women.

BACKGROUND: Age-related brain changes are well-documented and influenced by genetics. Extensive research links apolipoprotein E (apoE) to brain function, with the E4 allele serving as a risk factor for brain disease, including Alzheimer's disease, and the E2 allele conferring protection. Recent evidence also supports protective effects of another gene, human leukocyte antigen (HLA) DRB1*13, on brain disease and age-related brain atrophy in cognitively healthy adults. Here we investigated the effects of apoE and HLA DRB1*13 on brain function by examining changes in neural network properties with age in healthy adults. METHODS: One hundred seventy-eight cognitively healthy women (28-99 y old) underwent a magnetoencephalography scan and provided a blood sample for genetic analysis. Age-related changes in neural network variability in genetic subgroups of DRB1*13 × apoE genotype combinations were assessed using linear regression of network variability against age. FINDINGS: For individuals lacking a DRB1*13 allele and/or carrying an apoE4 allele, network variability increased significantly with age. In contrast, no such increase was observed in the presence of DRB1*13 and/or apoE2. INTERPRETATION: These findings extend previous research documenting the protective effect of DRB1*13 on brain structure to include protection against age-related changes in brain function, and demonstrate similar protective effects on neural network variability for either DRB1*13 or apoE2. These protective effects could be due to reduction or elimination of factors known to disrupt brain function, including neuroinflammation and amyloid beta protein. FUNDING: U.S. Department of Veterans Affairs, and University of Minnesota.