Pre-demential Motoric Cognitive Risk Syndrome in Ageing Subjects - Prediction of Cognitive Decline and Identification of Underlying Mechanisms

Alzheimer's disease (AD) is affecting more than 46.8 million people worldwide, making dementia one of the greatest public health challenges of the 21st century. The progression of AD is slow with a presymptomatic course over several years to decades, during which pathophysiological changes are underway, but the disease has not yet caused any noticeable symptoms to warrant a clinical diagnosis. A strong effort is ongoing to identify biomarkers preceding cognitive decline that can aid diagnosis and early intervention. Criteria for the motoric cognitive risk syndrome (MCR), including subjective cognitive decline (SCD) and slower preferred walking speed, but otherwise normal functioning, are powerful risk indicators of developing cognitive impairment and dementia. The presence of MCR is associated with a more than three-fold risk of developing dementia while the risk is only two-fold for SCD or slow gait alone. However, the pathophysiology of MCR is unknown and getting into the processes that cause such condition is needed to complement the MCR-based criteria and increase their predictive validity of cognitive decline and dementia. Impaired attentional control related to white matter alterations of presumed vascular origin may be responsible for the MCR phenotype. Individuals with SCD exhibit loss of white matter integrity in brain regions typically involved in attentional control, and abnormally slow gait has been linked to the disruption of white matter tracts associated with executive attention. Furthermore, a deeper understanding of MCR requires considering not only regional white matter changes but also the individuals' cognitive capacity to cope with brain damages, namely the cognitive reserve. Hence, the PRESAGE project intends to evaluate the interplay of white matter integrity and cognitive reserve on attentional control in MCR and non-MCR individuals aged 60 or older. Attentional control will be explored at both the behavioral and brain levels using dual-task challenges where individuals will have to divide attention between a cognitive (stroop) task and a motor task (walking). The working hypothesis is that the dual-task cost - a proxy of attentional control - is predictive of white matter abnormalities which, when adjusted for cognitive reserve, age and sex, should discriminate between MCR and non-MCR individuals. The project also includes a prospective, longitudinal study (two-year follow-up) whose purpose is to determine whether this marker, alone or in combination with other potentially relevant markers (i.e., neuropsychological, functional and chronobiological), have predictive value for conversion from MCR to mild cognitive impairment and dementia. Findings will increase knowledge about the pathophysiology of MCR and will contribute to improve MCR criteria and early identification of at-risk individuals.