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.

Survey among experts on the future role of tau-PET in clinical practice and trials.

Background: Recent advancements in Alzheimer's disease (AD) biomarker research and clinical trials prompt reflection on the value and consequently appropriate use of tau positron emission tomography (tau-PET) in the future.

Methods: We conducted an online survey among dementia and PET experts worldwide to investigate the anticipated future role of tau-PET in clinical practice and trials.

Results: Two hundred sixty-eight dementia experts, comprising 143 clinicians and 121 researchers, covering six continents participated.

Markers of amyloid-β deposition and burden of enlarged perivascular spaces in patients with cognitive impairment and small vessel disease.

MRI-visible enlarged perivascular spaces (EPVS) are common in patients with cognitive impairment and possibly linked to Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In a study of memory clinic patients (n = 450; mean age 66.5 ± 7.

CSF proteins of inflammation, proteolysis and lipid transport define preclinical AD and progression to AD dementia in cognitively unimpaired individuals.

This preclinical AD CSF proteome study identified a panel of 12-CSF markers detecting amyloid positivity and clinical progression to AD with high accuracy; some of these CSF proteins related to immune function, neurotrophic processes, energy metabolism and endolysosomal functioning (e.g., ITGB2, CLEC5A, IGFBP-1, CST3) changed before amyloid positivity is established.

Tele-neuropsychology in memory clinic settings: Reliability and usability of videoconference-based neuropsychological testing.

Objective: Neuropsychological assessment through VideoTeleConferencing (VTC) can help improve access to diagnostic and follow-up care in memory clinics. This study investigated the stability of performance on VTC assessment in relation to in-person assessment using a test-retest design and explored user experiences of VTC assessment.

Materials And Methods: Thirty-one patients (62 ± 6.

Comparing and linking the Mini-Mental State Examination and Montreal Cognitive Assessment in the Amsterdam Dementia Cohort.

Objectives: We aimed to compare and link the total scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), two common global cognitive screeners.

Methods: 2,325 memory clinic patients (63.2 ± 8.

Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of Frontotemporal Dementia.

Diagnosis of Frontotemporal dementia (FTD) and the specific underlying neuropathologies (frontotemporal lobar degeneration; FTLD- Tau and FTLD-TDP) is challenging, and thus fluid biomarkers are needed to improve diagnostic accuracy. We used proximity extension assays to analyze 665 proteins in cerebrospinal fluid (CSF) samples from a multicenter cohort including patients with FTD (n = 189), Alzheimer's Disease dementia (AD; n = 232), and cognitively unimpaired individuals (n = 196). In a subset, FTLD neuropathology was determined based on phenotype or genotype (FTLD-Tau = 87 and FTLD-TDP = 68).

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.

Background: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.

Serial Cerebrospinal Fluid Sampling Reveals Trajectories of Potential Synaptic Biomarkers in Early Stages of Alzheimer's Disease.

Background: Synaptic dysfunction is closely associated with cognitive function in Alzheimer's disease (AD), and is present already in an early stage of the disease.

Objective: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum.

Methods: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n = 50 amyloid-β+ [A +], n = 50 A-) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.