Publications by authors named "Pierre Jean Ousset"
Background: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology.
Objective: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion.
[Immunotherapies in Alzheimer's disease: state of the art and potential use in the elderly].
Geriatr Psychol Neuropsychiatr Vieil
June 2023
Article Synopsis
- Recent phase III clinical trials have shown promising results for anti-amyloid antibodies like lecanemab in improving cognitive function, quality of life, and caregiver burden in Alzheimer's patients.
- Aducanumab has already been approved for use in the U.S., but both treatments were primarily tested on younger participants without major health issues, meaning their effectiveness in older adults may not be fully understood.
- Concerns arise about using these treatments in elderly patients due to common conditions like cerebral microbleeds and long diagnosis delays, but subgroup analyses indicate they may still benefit those over 75, highlighting the need for careful evaluation of their risks and benefits in this age group.
Background: Fatigue is a common symptom in neurodegenerative diseases and is associated with decreased cognitive performances. A full knowledge of the causes and physiopathological pathways leading to fatigue in Alzheimer's disease could help treating this symptom and obtain positive effects on cognitive functions.
Objectives: To provide an overview of the clinical conditions and the biological mechanisms leading to fatigue in Alzheimer's disease patients.
Article Synopsis
- Lecanemab, an anti-amyloid antibody for early Alzheimer's Disease, received FDA accelerated approval in 2023, with ongoing regulatory review in Europe.
- An estimated 5.4 million people in the 27 EU countries could be eligible for treatment, with potential annual costs exceeding 133 billion EUR if priced similarly to the U.S.
- The European Alzheimer's Disease Consortium calls for equitable pricing policies and investments in research to ensure access to the drug, while addressing inequalities in health outcomes across European countries.
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.
Article Synopsis
- Recent FDA guidance supports the use of cognitive assessments as primary endpoints in early Alzheimer's trials, stressing the need to clarify their connection to dementia progression.
- A study involving 860 older adults with memory issues assessed the effectiveness of various neuropsychological markers over two years to predict dementia onset in the following three years.
- The Free and Cued Selective Reminding Test-Free Recall (FCSRT-FR) excelled in predicting dementia risk, while other common tests like the Mini-Mental State Examination did not show significant predictive value; thus, FCSRT and related fluency tasks are recommended as reliable markers for early dementia detection.
Objective: To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition.
Methods: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report.
Background: Administrative data are used in the field of Alzheimer's Disease and Related Syndromes (ADRS), however their performance to identify ADRS is unknown.
Objective: i) To develop and validate a model to identify ADRS prevalent cases in French administrative data (SNDS), ii) to identify factors associated with false negatives.
Methods: Retrospective cohort of subjects ≥ 65 years, living in South-Western France, who attended a memory clinic between April and December 2013.
Background/objectives: Cognitive decline associated with impaired kidney function might involve neurodegeneration. Our objectives were to evaluate the longitudinal association between kidney function and cognitive decline in older adults and to assess the involvement of cortical beta-amyloid and hippocampal atrophy (features of Alzheimer's disease (AD)) in this association.
Design: Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial (MAPT).
Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.
Int J Geriatr Psychiatry
February 2021
Objectives: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI.
Methods: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia.
Article Synopsis
- Recruitment for Alzheimer disease prevention trials struggles due to high screen-failure rates and low AD pathology prevalence among cognitively healthy individuals.
- The study examined participation rates and amyloid status in 16,877 individuals across four different prescreening cohorts, finding significant variability in participation depending on the cohort type.
- Key factors influencing participation included younger age, higher education levels, and male sex, with the participation rates ranging from 3% to 59% across different settings.
Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration.
Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration.
Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80).
Background: Neuropsychiatric symptoms (NPS) are prevalent in mild cognitive impairment (MCI), but we do not know much about their role in progression to dementia.
Objective: To investigate NPS and the risk of progression to probable Alzheimer's disease dementia (AD) among subjects with MCI.
Methods: 96 MCI participants were followed for 4 years.
Objectives: To study potentially modifiable factors associated with the severity of agitation or aggression (A/A) symptoms among Alzheimer's disease (AD) patients.
Design: Data from the Impact of Cholinergic Treatment Use (ICTUS) study, European longitudinal prospective observational study.
Setting: Community dwelling outpatients included in 29 European memory clinics.
Introduction: It is a challenge to find participants for Alzheimer's disease (AD) prevention trials within a short period of time. The European Prevention of Alzheimer's Dementia Registry (EPAD) aims to facilitate recruitment by preselecting subjects from ongoing cohort studies. This article introduces this novel approach.
View Article and Find Full Text PDFBackground: The relationship between cerebral microbleeds (CMB) and Alzheimer's disease (AD) has not yet been clearly determined, particularly with susceptibility weight-imaging (SWI).
Objective: To evaluate the SWI sequence using 3T MRI for the detection of CMB, and its ability to differentiate elderly control subjects (CS), stable mild cognitive impairment patients (MCI-s), MCI patients progressing to AD (MCI-p), and AD patients.
Methods: It was a prospective, monocentric, observational study that took place in Toulouse, France.
Background: The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation.
Methods: Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ)-α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ-α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APOE genotypes.
Background: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.
Methods: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco.
Objectives: Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population.
View Article and Find Full Text PDFIntroduction: Composite cognitive scores have been developed as primary outcome measures for preclinical/prevention trials for Alzheimer's disease (AD), mainly using observational data and with little consideration of clinical relevance.
Methods: Secondary analysis of placebo group data from a 5-year AD prevention trial. The composite score was the average of the following z scores: MMSE orientation items, Free and Cued Selective Reminding Test, Category Fluency, Trail Making Test-part B.
Background: Brain amyloid deposition is one of the key pathological hallmarks underlying the cognitive changes associated with Alzheimer's disease. Growing interest has been given to the earliest clinical manifestations of amyloid plaques. However, the relationship between amyloid status and activities of everyday function remains largely unknown.
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