Single and multidomain cognitive interventions to prevent cognitive impairment in “at risk” older adults

The estimates pointing for an increase in Alzheimer’s Disease (AD) prevalence in Europe, with a greater expression in Portugal, together with the lack of successful clinical trials on AD treatment lead to a focus in the development, application, and validation of interventions that could prevent conversion to AD. Existing Randomized Controlled Trials (RCTs) testing cognitive (CT) and multidomain interventions (MDT) efficacy to prevent AD presented limitations regarding the short-term follow-up, absence of sensitive/consistent outcome measures and unspecific targeted population (disregarding the individuals’ risk level to develop AD). Literature has pointed out that targeting at-risk older adults (e.g. Mild Cognitive Impairment-MCI or genetic risk for AD) is the best strategy to address an adequate assessment of these preventive interventions’ efficacy. Additionally, research has been scarce to examine effectively the functionality outcomes (considered by the WHO as primary outcomes) of CT and MDT. Following our previous research aimed at examining cognitive interventions efficacy through a comprehensive spectrum of cognitive and non-cognitive outcomes, the present proposal aims to examine, through an RCT design, the comparative effectiveness of CT and MDT in at-risk older adults, relatively to neurocognitive, neurobiological and functional outcomes, at short and long term follow-ups (6, 15 and 24 months). Ninety at-risk older adults (selected from three hospitals– Coimbra, Leiria, Aveiro) will be randomly assigned to a 6-month group intervention of CT, MDT and sham training (active control). Primary outcomes will be a composite score of global cognition and a performance-based functionality score. Secondary outcomes will be neurocognitive function (standardized neuropsychological test scores), neural plasticity markers (hippocampal volume, DMN connectivity) and neurodegeneration biomarkers (blood neurofilament light chain – NFL). Conversion rates to AD will be measured at the two longer follow-up time points. This project results will examine, for the first time, the interplay between neurocognitive, psychological, functional, and neurobiological outcomes of a non-pharmacological intervention in a population at increased risk to develop AD. We anticipate that findings taken from this project will have implications regarding the further development of larger and multicentric studies that could expand this comprehensive outcome measurement to other preventive interventions for this population. If our hypothesis is confirmed (primary outcomes improved in CT and MDT compared to control, and reduced conversion rates to AD in the experimental groups), these findings will hopefully have implications on the justification for the inclusion of these interventions in the National Plan for Dementia, fostering larger investment in this field, and enlarging the number of individuals that having assess to cognitive preventive interventions assess to it.