Motoric Cognitive Risk syndrome and physical activity: A window into the biology and disability of predementia A multi-center longitudinal Swiss study
Description: Dementia is a major public health issue, affecting 20’600 people in the Swiss Lemanic area. The onset of dementia is preceded by a predementia phase that can last several years and is often accompanied by behavioral changes including mobility impairments. This phase represents a crucial window for intervention and several treatments targeting distinct pathophysiological pathways are currently under investigation. However, the pathophysiological presentation and the clinical outcomes of predementia are highly heterogeneous and identifying those who will most likely benefit from early intervention remains a real challenge. Gait – a complex function relying on complex brain mechanisms – represents a good predictor of dementia and other poor age-related clinical outcomes. The presence of slow gait with a cognitive complaint defines the Motoric Cognitive Risk (MCR) syndrome, a predementia syndrome that predicts cognitive decline and dementia. The MCR syndrome has considerable clinical utility as it can be easily diagnosed in most clinical settings. In addition, the assessment of gait velocity and quantitative gait parameters can provide an indirect estimation of individual physical activity levels. In this regard, a possible link between MCR and physical activity is of key importance considering that physical inactivity is included among the few modifiable factors for dementia. MCR has been associated with vascular risk factors, but its pathophysiological substrates remain unclear. To fill these knowledge gaps, this multi-center longitudinal project focuses on the mobility dimension of predementia. The project aims at investigating the pathophysiological and neural mechanisms underlying MCR (Aim 1) and physical (in)activity in MCR patients (Aim 2), and to determine the value of MCR and of physical inactivity in predicting cognitive decline and secondary outcomes-including falls and stroke incidence-in relation to the implicated pathophysiological substrates (Aim 3), with a specific focus on the two main causes of dementia: Alzheimer’s pathology and cerebrovascular changes. These pathophysiological processes will be assessed in vivo in predementia patients of the two major Memory Centers of the Lemanic area-in Lausanne and Geneva-using advanced neuroimaging including multimodal MRI, molecular imaging (amyloid- and tau-PET), blood testing for Alzheimer’s disease (AD) biomarkers, and genetics. In addition, high-resolution ultra-high-field 7T MR imaging will be used in a subset of participants to fully characterize the cerebrovascular changes of MCR. Lifetime, present, and longitudinal physical activity levels will be assessed qualitatively and quantitatively using home-monitoring devices, disclosing the impact of MCR in real life. The findings of this project will have broad scientific relevance and a direct impact on clinical practice. By elucidating the pathophysiological substrates of MCR and their predictive value for cognitive decline in relation to Alzheimer’s and cerebrovascular etiologies, this study will provide new evidence to orient Memory Center policies for patient screening and management; and may help to individualize appropriate interventions. The characterization of brain tissues at ultra-high-field imaging will offer an unprecedent window into the heterogeneous presentations of small vessel disease in predementia, leading to a new comprehension of the cerebrovascular mechanisms that contribute to mobility and cognitive decline. This study will also elucidate the impact of physical activity on MCR and its contribution to cognitive decline in relation to pathophysiological processes, anticipating the development of targeted interventions. Finally, the multi-center nature of this project will consolidate the already effective collaborations between the Memory Centers of the Lemanic area, joining a national research and clinical effort for the prevention and treatment of dementia.
Amount: CHF 720,000
Funding type: research
Funder scheme: Project funding
Start date: 2024-04-01
End date: 2028-03-31
Investigator: Allali, Gilles
Institution: University of Lausanne – LA
Funded outputs count: 3
Funder award ID: 214855
OpenAlex ID: G8640522488