Clinical trial NCT05640141: Pre-demential Motoric Cognitive Risk Syndrome in Ageing Subjects
Official title: Pre-demential Motoric Cognitive Risk Syndrome in Ageing Subjects - Prediction of Cognitive Decline and Identification of Underlying Mechanisms
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Motoric Cognitive Risk Syndrome
Mild Cognitive Impairment
Alzheimer Disease
Dementia
Keywords: MRI
Cognition
Gait
Executive functions
Virtual reality
Motion capture
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2022-12-07
Enrollment: 160
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Controls : health volunteers without any reduced gait speed or cognitive complaint MCR : reduced gait speed, cognitive complaint Both : normal cognitive function

Brief summary: The main aim of the study is to characterize and understand the pathological mechanisms underlying the motoric cognitive risk syndrome, which is a predictor of Alzheimer disease.

Detailed description: 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.

Eligibility criteria: Inclusion criteria:

* Aged 55-75 years
* Right-handed as assessed by the Edinburgh Inventory
* Health Insurance
* Able to follow experimental instructions
* Consent
* Independent in daily life activities as assessed by Katz autonomy score, ADL and IADL

Inclusion criteria (MCR group specific)

* Reduced gait speed as assessed by the 4m or 10m walk test value compared to normative values (Bohannon \& Williams Andrews, 2011)
* Subjective cognitive complaint as assessed by dedicated questionnaire
* Subnormal cognitive function as assessed by the Montreal Cognitive Assessment (MoCA) test with score \> 23

Inclusion criteria (Controls group specific)

- Subnormal cognitive function as assessed by the Montreal Cognitive Assessment (MoCA) test with score \> 23

Exclusion criteria:

* Uncorrected visual or auditive deficits not allowing the realization of the experiment
* Evolutive disease (such as cancer)
* Active depression
* Neurological or psychiatric antecedent
* Neuromuscular impairment
* BMI \< 35
* Counter-indication to MRI

Primary outcomes:
measure: Prediction accuracy to detect MCR participants will be computed using Machine learning
timeFrame: Baseline
Secondary outcomes:
measure: MRI - Brain volumes
timeFrame: Baseline
measure: MRI - Connectivity
timeFrame: Baseline
measure: Gait - Dual task cost
timeFrame: Baseline
measure: Gait - Sensorimotor adaptation and savings
timeFrame: Baseline
Other outcomes:
Locations:
city: Caen
country: France
facility: CHU de Caen Normandie
Study officials:
affiliation: CHU de Caen Normandie
name: Pierre Denise, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: