TREM2 risk variants and associated endophenotypes in alzheimer's disease.

Background: Rare variants of the triggering receptor expressed on myeloid cell 2 (TREM2) gene are strong risk factors for Alzheimer's disease (AD), and drugs targeting the TREM2 protein are being developed. However, it is unknown what the effect of TREM2 variants is on the AD phenotype.

Methods: Here we studied a full range of clinical and biomarker measures in a large cohort of TREM2 variant carriers (n = 123, 7.

Enlarged cavum septum pellucidum as a neuroimaging signature of head impact exposure.

Cavum septum pellucidum (CSP) is commonly observed upon neuroimaging examination in individuals exposed to repetitive head impacts (RHI) and post-mortem in cases with chronic traumatic encephalopathy. Consequently, CSP has been proposed as a potential biomarker for RHI-related neurodegeneration, yet prevalence estimates of CSP across other neurodegenerative diseases and its clinical implications are largely unknown. We assessed CSP prevalence and clinical correlates in individuals with RHI exposure, a history of traumatic brain injury (TBI), a neurodegenerative disease (i.

Cerebral blood flow and cognitive functioning in patients undergoing transcatheter aortic valve implantation.

Background: Approximately one-third of patients with symptomatic severe aortic valve stenosis scheduled for transcatheter aortic valve implantation (TAVI) have some degree of cognitive impairment. The effect of TAVI on cardiac output, cerebral blood flow (CBF), and cognitive functioning has not been systematically studied.

Methods: CAPITA (NCT05481008) is a prospective longitudinal study assessing cerebral and cognitive outcomes in patients that underwent TAVI between August 2020 and October 2022.

Quantitative trait loci mapping of circulating metabolites in cerebrospinal fluid to uncover biological mechanisms involved in brain-related phenotypes.

Genomic studies of molecular traits have provided mechanistic insights into complex disease, though these lag behind for brain-related traits due to the inaccessibility of brain tissue. We leveraged cerebrospinal fluid (CSF) to study neurobiological mechanisms in vivo, measuring 5543 CSF metabolites, the largest panel in CSF to date, in 977 individuals of European ancestry. Individuals originated from two separate cohorts including cognitively healthy subjects (n = 490) and a well-characterized memory clinic sample, the Amsterdam Dementia Cohort (ADC, n = 487).

SCD-plus features and AD biomarkers in cognitively unimpaired samples: A meta-analytic approach for nine cohort studies.

Introduction: Specific features of subjective cognitive decline (SCD-plus) have been proposed to indicate an increased risk of preclinical Alzheimer's disease (AD). However, few studies have examined how these features relate to AD biomarkers in cognitively unimpaired (CU) older adults.

Methods: Meta-analyses were performed using cross-sectional data from nine cohorts (n = 7219, mean age (SD): 71.

Real-world datasets for the International Registry for Alzheimer's Disease and Other Dementias (InRAD) and other registries: An international consensus.

Background: Many dementia and Alzheimer's disease (AD) registries operate at local or national levels without standardization or comprehensive real-world data (RWD) collection. This initiative sought to achieve consensus among experts on priority outcomes and measures for clinical practice in caring for patients with symptomatic AD, particularly in the mild cognitive impairment and mild to moderate dementia stages.

Objective: The primary aim was to define a minimum dataset (MDS) and extended dataset (EDS) to collect RWD in the new International Registry for AD and Other Dementias (InRAD) and other AD registries.

Focus groups on digital cognitive assessment in the context of Alzheimer's disease.

Introduction: Digital cognitive assessments (DCAs) may facilitate early recognition of cognitive decline in the context of Alzheimer's disease (AD). While DCAs are increasingly emerging, they are often not used in practice. We assessed facilitators and barriers of using DCAs according to older individuals and patients.

Identifying pathways to the prevention of dementia: the Netherlands consortium of dementia cohorts.

Background: Aggregation of cohort data increases precision for studying neurodegenerative disease pathways, but efforts to combine data and expertise are often hampered by infrastructural, ethical and legal considerations. We aimed to unite various cohort studies in the Netherlands to enhance research infrastructure and facilitate research on dementia etiology and its public health implications.

Methods: The Netherlands Consortium of Dementia Cohorts (NCDC) includes participants with initially no established cognitive impairment from 9 Dutch cohorts: the Amsterdam Dementia Cohort (ADC), Doetinchem Cohort Study (DCS), European Medical Information Framework for Alzheimer's Disease (EMIF-AD), Longitudinal Aging Study Amsterdam (LASA), the Leiden Longevity Study (LLS), The Maastricht Study, the Memolife substudy of the Lifelines cohort, Rotterdam Study and Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study.

Needs expressed by people with subjective cognitive decline during amyloid PET disclosure consultations: An observational study.

Objectives: We disclosed amyloid PET results to people with subjective cognitive decline (SCD) and analysed audiotaped consultations. The aim was to examine the needs expressed by people with SCD and their care partners during amyloid PET disclosure consultations, and to explore neurologists' communication behaviours surrounding these expressions of need.

Methods: 53 persons with SCD (65 ± 7.

Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment.

DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment.

Prevalence of Pathogenic Variants and Eligibility Criteria for Genetic Testing in Patients Who Visit a Memory Clinic.

Background And Objectives: Identifying genetic causes of dementia in patients visiting memory clinics is important for patient care and family planning. Traditional clinical selection criteria for genetic testing may miss carriers of pathogenic variants in dementia-related genes. This study aimed identify how many carriers we are missing and to optimize criteria for selecting patients for genetic counseling in memory clinics.

Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study.

Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Amyloid-related changes in fluency in patients with subjective cognitive decline.

Introduction: We examined semantic and phonemic fluency in individuals with subjective cognitive decline (SCD) in relation to amyloid status and clinical progression.

Methods: A total of 490 individuals with SCD (62 ± 8 years, 42% female, 28% amyloid-positive, 17% clinical progression) completed annual fluency assessments (mean ± SD follow-up 4.3 ± 2.

Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry.

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.

Tract-specific white matter hyperintensities and neuropsychiatric syndromes: a multicentre memory clinic study.

Background: White matter hyperintensities (WMH) have been implicated in the pathogenesis of neuropsychiatric symptoms of dementia but the functional significance of WMH in specific white matter (WM) tracts is unclear. We investigate whether WMH burden within major WM fibre classes and individual WM tracts are differentially associated with different neuropsychiatric syndromes in a large multicentre study.

Method: Neuroimaging and neuropsychiatric data of seven memory clinic cohorts through the Meta VCI Map consortium were harmonised.

Separating dementia with Lewy bodies from Alzheimer's disease dementia using a volumetric MRI classifier.

Objectives: Distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) dementia, particularly in patients with DLB and concomitant AD pathology (DLB/AD+), can be challenging and there is no specific MRI signature for DLB. The aim of this study is to examine the additional value of MRI-based brain volumetry in separating patients with DLB (AD+/-) from patients with AD and controls.

Methods: We included 1518 participants from four cohorts (ADC, ADNI, PDBP and PredictND); 147 were patients with DLB (n = 76, DLB/AD+; n = 71, DLB/AD-), 668 patients with AD dementia, and 703 controls.

Analytical and clinical performance of eight Simoa and Lumipulse assays for automated measurement of plasma p-tau181 and p-tau217.

Background: Among the Alzheimer's disease (AD) biomarkers measured in blood, phosphorylated forms of tau (p-tau) have been shown to exhibit a particularly high diagnostic potential. Here, we performed a comprehensive method comparison study, followed by evaluation of the diagnostic performance of eight recent plasma p-tau immunoassays targeting different tau phosphorylation sites, different tau fragments, and that are measured by two distinct platforms.

Methods: We enrolled a cohort of 40 patients with AD at the stage of dementia (AD-dem) characterized by positive CSF A + T + profile, and a control group of 40 cognitively healthy participants (Control), to conduct a comprehensive method comparison for three plasma p-tau181 and five plasma p-tau217 assays run on the Simoa HD-X™ or Lumipulse G600II/G1200 platforms.

Defining benefit: Clinically and biologically meaningful outcomes in the next-generation Alzheimer's disease clinical care pathway.

To understand the potential benefits of emerging Alzheimer's disease (AD) therapies within and beyond clinical trial settings, there is a need to advance current outcome measurements into meaningful information relevant to all stakeholders. The relationship between the impact on disease biology and clinically measurable outcomes in cognition, function, and behavior must be considered when defining the meaningful benefit of early AD therapies. In this review, we discuss: (1) the lack of consideration for biomarkers in the current concept of meaningfulness in AD; (2) the lack of gold standards for determining minimal biologically and clinically important differences (MBCIDs) in AD trials; (3) how the treatment benefits of disease-modifying treatments are cumulative and increase over time; and (4) the different concepts of meaningfulness among key stakeholders.

A Machine Learning Model to Harmonize Volumetric Brain MRI Data for Quantitative Neuroradiologic Assessment of Alzheimer Disease.

Purpose To extend a previously developed machine learning algorithm for harmonizing brain volumetric data of individuals undergoing neuroradiologic assessment of Alzheimer disease not encountered during model training. Materials and Methods Neuroharmony is a recently developed method that uses image quality metrics as predictors to remove scanner-related effects in brain-volumetric data using random forest regression. To account for the interactions between Alzheimer disease pathology and image quality metrics during harmonization, the authors developed a multiclass extension of Neuroharmony for individuals with and without cognitive impairment.

The need for personalization when sharing results of amyloid imaging for Alzheimer's disease: Insights from a randomized experimental study.

Objective: To study information needs after receiving abnormal amyloid-PET results, and how individual characteristics moderate effects of different communication strategies on information recall.

Methods: In an online video-vignette experiment, seven vignettes each depicted a consultation of a physician sharing abnormal amyloid-PET results with a patient with Mild Cognitive Impairment(MCI), using different communication strategies. Healthy individuals (N = 1017; age 64 ± 8, 808(79 %) female), instructed to imagine themselves as the video-patient, viewed a randomly-assigned vignette and completed questionnaires to assess information needs and test moderation effects of gender, age, care-partner experience, health literacy, and coping.

Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia.

Background: The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods: We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN).

Performance of plasma p-tau217 and NfL in an unselected memory clinic setting.

Introduction: Plasma phosphorylated tau-217 (p-tau217) and neurofilament light (NfL) can differentiate between different dementias in selected cohorts. We aim to test the discrimination potential of these markers in a real-world cohort.

Methods: We measured p-tau217 (ALZpath) and NfL (Quanterix) in 415 (unselected) consecutive memory clinic patients.