Approved research

Genetics of reserve capactiy and underlying functional brain differences.

Lay summary

A major aim of the UK Biobank is to better understand the genetics and brain changes underlying dementia and other serious disease for the improvement of diagnosis and treatment of such disease. One influential factor in this respect is reserve capacity, that is the ability to maintain cognitive abilities relatively well in the presence of neurodegeneration. We previously found that higher resting-state fMRI assessed hub connectivity in the left frontal cortex is a promising candidate brain substrate of reserve capacity in normal aging and Alzheimer's disease (Franzmeier et al. Neurology, 2017). However, the genetic contribution to reserve capacity is only poorly understood. Here, we aim to investigate the genetics underlying the functional brain mechanisms that maintain cognition in aging and disease. For this purpose, we will conduct a genome-wide association study (GWAS) to identify any SNPs that are associated with resting state functional connectivity of the left frontal cortex (hub in the Broca area) and on this basis compute a polygenetic "reserve score" (PRS). For the second aim, we will test whether cross-sectional and longitudinal cognitive performance can be predicted by the PRS (criterion of cognitive benefit). Furthermore, we aim to assess the genetic overlap between left frontal hub connectivity and classical measures of reserve capacity, such as intelligence and education (criterion of construct validity). In a final (more explorative) step, we will examine the relationship between the PRS and participants' life style factors (e.g. physical activity).