Approved Research

Unravelling the link between cardiometabolic disorders and brain health-The contribution of sex-differences

Lay summary

Dementia is the clinical manifestation of decades of accumulating neuropathology and today it represents a public health priority without a cure. Therefore, prevention is necessary and feasible by tackling a constellation of risk factors, such as cardiovascular and metabolic disorders-hereafter, cardiometabolic disorders (CMDs). The effects of comorbid CMDs on the brain and the resilience mechanisms are poorly understood as the role of sex-differences. Moreover, in old age, comorbid CMDs co-occur with complications deriving by damages to other organs in the body, especially in the kidney, liver, and lung. The interplay between CMDs and comorbid kidney/liver/lung disorders in relation to cognition and brain pathology remained unexplored.

This project represents a first step towards understanding to what extent CMDs, commonly clustering together in old age, as well as their common comorbidities (kidney, liver, and lung disorders) influence cognition and the brain. Moreover, this project seeks to identify groups of modifiable risk and protective factors that contribute to biological markers of brain resilience during lifespan and might be able to counteract the harmful effect of CMDs on cognitive and brain health. Finally, systematic differences between the sexes as well as between individual with different genetic predisposition to dementia will be addressed in all the panned studies.

We believe that findings from this project will help healthcare professionals with suggestions to develop increasingly personalized preventive strategies and interventions to promote brain and cognitive health. Indeed, albeit there is no cure, dementia can be prevented if healthcare professionals (1) act timely, (2) target modifiable factors simultaneously, and (3) implement more individualized strategies. And our project, seeking to shed the light on the interplay between several common comorbid age-related disorders (CMDs and their kidney/liver/lung comorbidities) on cognitive and brain heath, is well aligned with these three points.

Data from the full cohort, and derived sub-cohorts (e.g., with available brain magnetic resonance imaging and/or cognitive assessment) will be used in data analyses.