Prediction of dementia risk from multimodal repeated measures: The added value of brain MRI biomarkers.

Abstract: The utility of brain magnetic resonance imaging (MRI) for predicting dementia is debated. We evaluated the added value of repeated brain MRI, including atrophy and cerebral small vessel disease markers, for dementia prediction. We conducted a landmark competing risk analysis in 1716 participants of the French population-based Three-City Study to predict the 5-year risk of dementia using repeated measures of 41 predictors till year 4 of follow-up.

Associations Between Blood-Based Biomarkers and Cognitive and Functional Trajectories Among Participants of the MEMENTO Cohort.

Background And Objectives: Elevated levels of Alzheimer disease (AD) blood-based biomarkers are associated with accelerated cognitive decline. However, their distinct relationships with specific cognitive and functional domains require further investigation. We aimed at estimating the associations between AD blood-based biomarkers and the trajectories of distinct cognitive and functional domains over a 5-year follow-up period.

Explaining the Variability of Alzheimer Disease Fluid Biomarker Concentrations in Memory Clinic Patients Without Dementia.

Background And Objectives: Patients' comorbidities can affect Alzheimer disease (AD) blood biomarker concentrations. Because a limited number of factors have been explored to date, our aim was to assess the proportion of the variance in fluid biomarker levels explained by the clinical features of AD and by a large number of non-AD-related factors.

Methods: MEMENTO enrolled 2,323 individuals with cognitive complaints or mild cognitive impairment in 26 French memory clinics.

Contribution of Global Amyloid-PET Imaging for Predicting Future Cognition in the MEMENTO Cohort.

Background And Objectives: Global amyloid-PET is associated with cognition and cognitive decline, but most research on this association does not account for past cognitive information. We assessed the prognostic benefit of amyloid-PET measures for future cognition when prior cognitive assessments are available, evaluating the added value of amyloid measures beyond information on multiple past cognitive assessments.

Methods: The French MEMENTO cohort (a cohort of outpatients from French research memory centers to improve knowledge on Alzheimer disease and related disorders) includes older outpatients with incipient cognitive changes, but no dementia diagnosis at inclusion.

Understanding the relationship between type-2 diabetes, MRI markers of neurodegeneration and small vessel disease, and dementia risk: a mediation analysis.

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk. The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels.

Understanding factors associated with the trajectory of subjective cognitive complaints in groups with similar objective cognitive trajectories.

Background: Cognitive complaints are often regarded as an early sign of Alzheimer's disease (AD) but may also occur in several other conditions and contexts. This study examines the correlates of cognitive complaint trajectories over a 5-year period in individuals who shared similar objective cognitive trajectories.

Methods: We analyzed a subsample (n = 1748) of the MEMENTO cohort, consisting of individuals with subjective cognitive decline or mild cognitive impairment at baseline.

Complexities of cerebral small vessel disease, blood pressure, and dementia relationship: new insights from genetics.

Importance: There is increasing recognition that vascular disease, which can be treated, is a key contributor to dementia risk. However, the contribution of specific markers of vascular disease is unclear and, as a consequence, optimal prevention strategies remain unclear.

Objective: To disentangle the causal relation of several key vascular traits to dementia risk: (i) white matter hyperintensity (WMH) burden, a highly prevalent imaging marker of covert cerebral small vessel disease (cSVD); (ii) clinical stroke; and (iii) blood pressure (BP), the leading risk factor for cSVD and stroke, for which efficient therapies exist.

Predicting sojourn times across dementia disease stages, institutionalization, and mortality.

Introduction: Inferring the timeline from mild cognitive impairment (MCI) to severe dementia is pivotal for patients, clinicians, and researchers. Literature is sparse and often contains few patients. We aim to determine the time spent in MCI, mild-, moderate-, severe dementia, and institutionalization until death.

Disease progression model anchored around clinical diagnosis in longitudinal cohorts: example of Alzheimer's disease and related dementia.

Background: Alzheimer's disease and related dementia (ADRD) are characterized by multiple and progressive anatomo-clinical changes including accumulation of abnormal proteins in the brain, brain atrophy and severe cognitive impairment. Understanding the sequence and timing of these changes is of primary importance to gain insight into the disease natural history and ultimately allow earlier diagnosis. Yet, modeling changes over disease course from cohort data is challenging as the usual timescales (time since inclusion, chronological age) are inappropriate and time-to-clinical diagnosis is available on small subsamples of participants with short follow-up durations prior to diagnosis.

Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.

Evaluating the harmonisation potential of diverse cohort datasets.

Data discovery, the ability to find datasets relevant to an analysis, increases scientific opportunity, improves rigour and accelerates activity. Rapid growth in the depth, breadth, quantity and availability of data provides unprecedented opportunities and challenges for data discovery. A potential tool for increasing the efficiency of data discovery, particularly across multiple datasets is data harmonisation.

Forecasting individual progression trajectories in Alzheimer's disease.

The anticipation of progression of Alzheimer's disease (AD) is crucial for evaluations of secondary prevention measures thought to modify the disease trajectory. However, it is difficult to forecast the natural progression of AD, notably because several functions decline at different ages and different rates in different patients. We evaluate here AD Course Map, a statistical model predicting the progression of neuropsychological assessments and imaging biomarkers for a patient from current medical and radiological data at early disease stages.

How Traumatic Brain Injury History Relates to Brain Health MRI Markers and Dementia Risk: Findings from the 3C Dijon Cohort.

Background: The long-term effects of traumatic brain injury (TBI) with loss of consciousness (LOC) on magnetic resonance imaging (MRI) markers of brain health and on dementia risk are still debated.

Objective: To investigate the associations of history of TBI with LOC with incident dementia and neuroimaging markers of brain structure and small vessel disease lesions.

Methods: The analytical sample consisted in 4,144 participants aged 65 and older who were dementia-free at baseline from the Three City -Dijon study.

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort.

Introduction: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood.

Methods: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment.

Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort.

Background And Objective: Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints.

Methods: The MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics.