Publications by authors named "Julien Dumurgier"

Background: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.

Method: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n=104), Alzheimer’s disease (AD, n=76) and neurological controls (NC, n=27).

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Background: Patients with bipolar disorder (BD) are at increased risk of dementia. The underlying mechanisms are debated. FDG-PET elucidates glucose metabolic reductions due to altered neuronal activity in the cerebral cortex, allowing detection and identification of neurodegenerative processes.

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  • Recent advancements in Alzheimer's treatment now require verification of amyloid-β pathology using PET scans or cerebrospinal fluid, but blood tests could simplify this process.* -
  • A study involving nearly 7,000 individuals identified that the plasma biomarker p-tau217 can reliably indicate amyloid-β pathology, especially in patients with probable Alzheimer’s dementia.* -
  • The findings suggest that combining p-tau217 results with clinical assessments may allow for accurate diagnoses without the need for more invasive PET or CSF tests.*
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  • The study investigates the relationship between plasma neurofilament light (NfL) protein levels and cognitive impairment across various patient groups, including Alzheimer’s disease and other dementias.
  • The research was conducted on 320 patients, measuring NfL levels and assessing cognitive performance, with significant associations found between higher NfL levels and lower cognition, particularly in memory and executive functions.
  • Despite noteworthy findings, the clinical application of plasma NfL in daily practice for unselected cognitive impairment patients remains largely unaddressed.
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  • Research indicates that plasma biomarkers related to amyloid, tau, neurodegeneration, and neuroinflammation could be useful in diagnosing dementia, but their effectiveness for diagnosing dementia with Lewy bodies (DLB) specifically remains unclear.
  • A study involving patients with DLB, Alzheimer's disease (AD), and neurological controls measured various plasma biomarkers and found that DLB patients had altered biomarker levels compared to controls and AD patients.
  • Plasma p-tau181 was the most effective biomarker for distinguishing DLB from AD and controls, suggesting it plays a key role in identifying amyloid-related issues in DLB, although the overall diagnostic performance of these biomarkers was moderate.
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Background: The ε4 allele of the apolipoprotein E gene (APOE4) plays a role in neurodegeneration and in cardiovascular disease, but findings on its association with mortality are inconsistent. We aimed to examine the association between APOE4 and mortality, and the role of dementia in this association.

Methods: In this pooled analysis, data on White participants aged 45-90 years who underwent APOE genotyping were drawn from two population-based cohorts: the Whitehall II study (UK), which began in 1985 and is ongoing, and the Three-City study (France), initiated in 1999 and ended in 2012.

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  • - Psychosis, marked by delusions and hallucinations, is common in Alzheimer's and other neurodegenerative dementias, leading to challenges in diagnosis and treatment.
  • - A systematic review of 98 studies reveals high prevalence rates of psychotic symptoms across different dementias, with notable patterns such as misidentification delusions in dementia with Lewy bodies and paranoid ideas in Alzheimer's.
  • - The findings highlight significant variations in psychotic symptoms among different neurodegenerative diseases, emphasizing the need for more research on early-stage psychosis to improve diagnosis and management.
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Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD).

Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients.

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  • Adiponectin is a special protein related to how our body uses energy and deals with fats and sugars.
  • Researchers looked at how this protein might be connected to Alzheimer's disease (AD) by reviewing many studies from the past ten years.
  • While lab studies showed that adiponectin could help protect against AD, studies on people didn't find clear results, meaning more research is needed to understand its true effects.
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Post-mortem staging of Alzheimer's disease (AD) neurofibrillary pathology is commonly performed by immunohistochemistry using AT8 antibody for phosphorylated tau (p-tau) at positions 202/205. Thus, quantification of p-tau205 and p-tau202 in cerebrospinal fluid (CSF) should be more reflective of neurofibrillary tangles in AD than other p-tau epitopes. We developed two novel Simoa immunoassays for CSF p-tau205 and p-tau202 and measured these phosphorylations in three independent cohorts encompassing the AD continuum, non-AD cases and cognitively unimpaired participants: a discovery cohort (n = 47), an unselected clinical cohort (n = 212) and a research cohort well-characterized by fluid and imaging biomarkers (n = 262).

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Background: Obesity is associated with disability but whether age and ageing modify this association remains unclear. We examined whether this association changes between 50 and 90 years, and whether change in disability rates over 14 years differs by body mass index (BMI) categories.

Methods: BMI and ADL-disability data on 28,453 individuals from 6 waves (2004-2018, SHARE study) were used to examine the cross-sectional absolute and relative associations, extracted at age 50, 60, 70, 80, and 90 years using logistic mixed models.

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Plasma neurofilament light chain (NfL) is a promising biomarker of axonal damage for the diagnosis of neurodegenerative diseases. Phosphorylated neurofilament heavy chain (pNfH) has demonstrated its value in motor neuron diseases diagnosis, but has less been explored for dementia diagnosis. In a cross-sectional study, we compared cerebrospinal fluid (CSF) and plasma NfL and pNfH levels in n = 188 patients from Lariboisière Hospital, Paris, France, including AD patients at mild cognitive impairment stage (AD-MCI, n = 36) and dementia stage (n = 64), non-AD MCI (n = 38), non-AD dementia (n = 28) patients and control subjects (n = 22).

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  • The study investigates how the initial symptoms of dementia with Lewy bodies (DLB) influence patient outcomes and mortality.
  • Conducted at four French neurological centers, the research categorizes patients into groups based on whether their first symptoms were cognitive, psychiatric, or motor.
  • Out of 310 patients analyzed, those in the motor group exhibited more severe clinical symptoms, but the initial symptoms did not significantly impact overall mortality rates.
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Introduction: The association of lipids with dementia remains a subject of debate. Using data from 7,672 participants of the Whitehall II prospective cohort study, we examined whether timing of exposure, length of follow-up, or sex modifies this association.

Methods: Twelve markers of lipid levels were measured from fasting blood and eight among them a further five times.

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  • The study aimed to investigate if the profiles of behavioral and psychological symptoms of dementia (BPSD) vary according to the type of dementia in patients with severe BPSD.
  • Researchers analyzed data from 398 patients diagnosed with different types of dementia, including Alzheimer's, frontotemporal, Lewy body/Parkinsonian, and vascular dementia.
  • Results showed distinct neuropsychiatric symptom profiles based on the dementia type, with Lewy body/PD patients exhibiting more hallucinations and anxiety, while frontotemporal dementia patients showed less delusions but more disinhibition.
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Background: Alzheimer's disease (AD) is the 5th leading cause of death in people 65 years and older. The ATN classification reflects a biological definition of AD pathology with markers of Aβ deposition (A), pathologic tau (T), and neurodegeneration (N). Little is known about the relationship between ATN status and the risk of mortality, leading us to examine this association in a relatively large population of patients seen at a memory clinic for cognitive disorders.

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  • The study aimed to evaluate geriatrics residents' self-confidence and skills in performing lumbar punctures (LP) and explored the benefits of using simulation and virtual reality for training.
  • A survey found that an overwhelming majority of residents recognized the need for LP competency and supported additional practical training, while participants in simulated training praised its effectiveness.
  • Results showed a significant improvement in residents' self-assessed skills after training, leading to an 85.8% success rate in actual clinical practice, highlighting the potential of simulation-based training for enhancing confidence and performance.
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  • CSF p-tau235 is a promising biomarker for detecting symptomatic Alzheimer's disease (AD) and was analyzed in real-world clinical settings rather than just controlled research studies.
  • This multicenter study involved measuring CSF p-tau235 in patients from two independent memory clinics with various cognitive conditions, while comparing it to other established biomarkers (p-tau181, p-tau217, and p-tau231).
  • Results showed that higher levels of CSF p-tau235 were strongly linked to amyloid beta positivity, indicating its potential as a diagnostic tool for AD, with accuracy rates similar to some existing biomarkers but not as high as p-tau217.
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Objective: To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice.

Methods: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology.

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  • Metabolic dysfunction and leptin signaling have been linked to Alzheimer's disease (AD), leading researchers to investigate the connections between plasma leptin levels and various biomarkers related to cognitive impairment.
  • The study analyzed data from over 1,000 cognitively impaired patients and found that those diagnosed with AD had significantly lower plasma leptin levels compared to those without amyloid-related issues.
  • The results suggest a potential link between leptin metabolism and brain amyloid deposition, indicating that plasma leptin levels might play a role in diagnosing and understanding AD pathophysiology.
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  • The study investigated cerebrospinal fluid (CSF) alpha-synuclein levels to distinguish between Dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD), as abnormal aggregation of this protein is linked to DLB.
  • The results showed significantly lower CSF alpha-synuclein levels in DLB patients compared to those with AD and established a potential diagnostic threshold with high sensitivity and specificity.
  • The findings suggest that measuring CSF alpha-synuclein could aid in the early diagnosis of DLB in conjunction with other biomarkers, although it was not associated with specific brain atrophy patterns.
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Background: There is consistent evidence of social inequalities in dementia but the mechanisms underlying this association remain unclear. We examined the role of smoking in midlife in socioeconomic differences in dementia at older ages.

Methods: Analyses were based on 9951 (67% men) participants, median age 44.

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This cross-sectional study analyzes 10-year trends in sales of Alzheimer disease drugs in France compared with trends in the UK, Spain, and Germany.

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