MCR Syndrome in Quebec : Results From NuAge Study

Study Overview
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Brief Summary
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The overall objective of the proposal is to examine the epidemiology of the newly reported motoric cognitive risk (MCR) syndrome, which is a pre-dementia syndrome combining subjective cognitive complaint (i.e.; memory complaint) with objective slow gait speed, in the Quebec elderly population. Cognition and locomotion are two human abilities controlled by the brain. Their decline is highly prevalent with physiological and pathological aging, and is greater than the simple sum of their respective prevalence, suggesting a complex age-related interplay between cognition and locomotion. Both declines in cognition and locomotion are associated, furthermore the temporal nature of their association has been unclear for a long time. Recently, a systematic review and meta-analysis has provided evidence that poor gait performance predicts dementia and, in particular, has demonstrated that MCR syndrome is a pre-dementia syndrome, suggesting that low gait performance is the first symptom of dementia. The uniqueness of MCR syndrome is that it does not rely on a complex evaluation or laboratory investigations. Indeed, this syndrome combined subjective cognitive complaint and objective slow gait speed, and is easy to apply in population-based settings. Prevalence and incidence of MCR syndrome, as well as its association with incidence of cognitive decline and impairment, have never been reported in Canada. Nutrition as a determinant of successful aging: The Quebec longitudinal Study (the NuAge study) is a Quebec population-based observational cohort study performed in healthy older community-dwellers adults which provides a unique opportunity to: 1) obtain reliable estimates of MCR syndrome prevalence and incidence, 2) determine the distribution of clinical and biological (blood biomarkers and genetic) characteristics associated with MCR syndrome, 3) examine the association of MCR syndrome and its biological characteristics with cognitive decline and incidence of cognitive impairment in the Quebec elderly population.

Official Title
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The Motoric Cognitive Risk Syndrome in the Quebec Population: Results From the NuAge Study - Sub-study: The Biological Underpinnings of Motoric Cognitive Risk Syndrome: a Multicenter Study

Conditions
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Motoric Cognitive Risk Syndrome, Aging Disorder

Intervention / Treatment
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* Other: Data analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All included participants of NuAge Study Exclusion Criteria: no information about cognitive complaint in NuAge database no measure of walking speed in NuAge database no follow-up completed in NuAge database
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MCR syndroms<br>Summarize of participants' characteristics using means and standard deviations or frequencies and percentages First, prevalence of MCR syndrome will be determined by classifying participants into MCR and non-MCR syndrome groups. Second, between-group comparisons of participants' characteristics will be performed using unpaired t-test, Mann-Whitney, analysis of variance with LSD correction or Chi-square test, as appropriate. Third, multiple regressions will be performed to examine the association between MCR syndrome (dependent variable) and cardio-vascular risk factors and/or diseases (independent variables) adjusted on participants' characteristics. Fourth, the incidence of MCR syndrome during the follow-up period of NuAge study will be reported. Fifth, regression will be performed to examine the association between MCR syndrome (dependent variable) and cognitive decline as well cognitive impairment (independent variables, separated model) adjusted on participants' characteristics. | Other: Data analysis<br>* No intervention, data analysis only<br>|
| Non MCR syndroms<br>Summarize of participants' characteristics using means and standard deviations or frequencies and percentages First, prevalence of MCR syndrome will be determined by classifying participants into MCR and non-MCR syndrome groups. Second, between-group comparisons of participants' characteristics will be performed using unpaired t-test, Mann-Whitney, analysis of variance with LSD correction or Chi-square test, as appropriate. Third, multiple regressions will be performed to examine the association between MCR syndrome (dependent variable) and cardio-vascular risk factors and/or diseases (independent variables) adjusted on participants' characteristics. Fourth, the incidence of MCR syndrome during the follow-up period of NuAge study will be reported. Fifth, regression will be performed to examine the association between MCR syndrome (dependent variable) and cognitive decline as well cognitive impairment (independent variables, separated model) adjusted on participants' characteristics. | Other: Data analysis<br>* No intervention, data analysis only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevalence of MCR syndrome | Diagnosis of MCR syndrome following Verghese et al. criteria | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive decline and impairment | Modified Mini-Mental State (3MS) in the NuAge study. | 3 years | 
| Covariates | Cardio-vascular risk factors and diseases assessed using reported health condition | 3 years | 
| Covariates | Cardio-vascular risk factors and diseases assessed using physical examination: body mass index | 3 years | 
| Covariates | Cardio-vascular risk factors and diseases assessed using physical examination: hip waist ratio from hip and waist circumference | 3 years | 
| Covariates | Cardio-vascular risk factors and diseases assessed using physical examination: blood pressure (value of systolic, diastolic when participants are seated in an upright position in a chair) | 3 years | 
| Biological characteristics | we selected biomarkers that consistently show associations with clinical risk factors for MCR : IL-6, high-sensitivity CRP and Malondialdehyde (MDA). These biomarkers are associated with individual MCR components. CRP was associated with plaques. Inflammation is hypothesized to be a precursor to neurofibrillary tangles and amyloid plaques; hallmarks of AD. Oxidative stress damage is elevated in vulnerable brain regions in early AD and MCI. We propose a multi-level examination of vascular pathways in MCR including biomarkers (CRP and homocysteine). We include homocysteine, a vascular biomarker, linked to gait and cognitive deficits in other studies. | 3 years | 
| Genetic approach | we propose to derive polygenic risk scores for cognitive and obesity phenotypes in NuAge, and to examine its predictive validity for MCR syndrome and incident cognitive impairment | 3 years |