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.

Long‐Term Impact of Amyloid PET in Memory Clinic Diagnostic Workup: A Matched Cohort Study on Healthcare Costs, Institutionalisation, and Mortality Risk.

Background: We hypothesise that improved diagnostic precision, operationalised by adding amyloid positron emission tomography (PET) to the diagnostic work‐up in a memory clinic, is beneficial for long‐term health and healthcare cost outcomes. We investigated whether a more precise diagnosis influenced institutionalisation and mortality incidence trajectories, and annual healthcare costs over a period up to eight years.

Method: Between October 2014 and December 2016, patients from the Amsterdam Dementia Cohort were offered an amyloid‐PET as part of their diagnostic work‐up.

Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease.

Background: There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity‐based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Differences in protein expression in Alzheimer’s disease patients based on risk factors for amyloid‐related imaging abnormalities.

Background: The exact mechanism underlying amyloid‐related imaging abnormalities (ARIA) is unknown. Several factors explain ARIA risk, including the presence of microbleeds, APOE4 carriership, and very low Aβ42 levels. The cerebrospinal fluid (CSF) proteome reflects ongoing mechanisms and, thereby, provides an accessible fluid to refine risk of ARIA development.

Exploring barriers and facilitators for the implementation of Alzheimer’s disease blood‐based biomarkers in primary care: The CANTATE‐Perspectives study.

Background: Adequately diagnosing Alzheimer’s disease (AD) in primary care can be challenging. Early symptoms often go unrecognized and other (neurodegenerative) diseases may be misdiagnosed as AD. AD blood‐based biomarkers could improve the diagnostic process for cognitive complaints in primary care.

Using a blood‐based biomarker panel for Alzheimer’s disease to determine eligibility for disease modifying treatment in a memory clinic setting: three scenarios.

Background: Blood‐based biomarkers (BBM) for Alzheimer’s disease (AD) may be able to identify individuals eligible for emerging anti‐amyloid treatments (DMT). We aimed to evaluate how to use BBM as (pre‐) selection tools for DMTs by simulating different triaging scenarios in a memory clinic setting.

Methods: We included 1199 participants from the Amsterdam Dementia Cohort with measured BBM (plasma pTau181, GFAP and NfL) and used a predefined Youden‐index based cut point for amyloid positivity (method: https://doi.

The impact of tau‐PET in a selected memory clinic cohort: design and rationale of the TAP‐TAU study.

Background: Tau‐PET is a diagnostic tool with high sensitivity and high specificity for discriminating Alzheimer Disease (AD) dementia from other neurodegenerative disorders in well‐controlled research environments. The role of tau‐PET in “real‐world” clinical practice, however, remains to be established. We hypothesize that tau‐PET will lead to some changes of the pre‐PET clinical diagnosis and will improve diagnostic certainty and patient management in patients with considerable diagnostic uncertainty.

The prevalence of tau‐PET positivity in aging and dementia.

Background: Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e.

Combination of CSF synaptic biomarkers and qEEG leads to a better prediction of disease progression in Alzheimer’s disease.

Background: Synaptic dysfunction plays an important role in Alzheimer’s disease (AD) and cognitive decline. We investigated the association between cerebrospinal fluid (CSF) synaptic protein levels and quantitative EEG (qEEG) measures, two modalities to measure synaptic dysfunction in AD pathology. We assessed combined and independent prognostic value of both modalities for cognitive decline along the AD continuum.

CSF ATN and α‐synuclein co‐pathology in AD, PD, and DLB.

Background: Co‐pathology between Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) remains poorly understood but is relevant for trial design. We aimed to compare CSF markers of amyloid, tau, and neurodegeneration (ATN) and α‐synuclein between AD, PD, DLB and controls, and investigate the influence of demographical, genetic, and clinical factors on amyloid positivity.

Method: As part of the EPND study, we included 337 individuals with AD, PD, DLB and controls from 6 centers.

Unravelling the role of subcortical brain volumes in the conversion to dementia: a multi‐cohort analysis.

Background: Hippocampal volume is an acknowledged biomarker of neurodegenerative disease, including Alzheimer’s disease (AD). However, the relationship between other subcortical brain structures and dementia risk is uncertain and may differ by disease stage. We aimed to assess the prognostic value of subcortical volumes for dementia risk across different disease stages by investigating memory clinic‐based populations and community‐dwelling individuals.

Clinical consequences of the Alzheimer’s blood‐based biomarker panel: a prospective evaluation in memory clinics ‐ the CANTATE project.

Background: Blood‐based biomarkers (BBM) are emerging as minimally invasive, scalable and relatively low‐cost options for discriminating different neurodegenerative diseases. Before implementation in clinical practice can take place, it is important to determine their real‐world clinical validity in patients presenting at a memory clinic. Therefore, we prospectively evaluated changes in diagnosis and diagnostic confidence resulting from the use of a BBM panel tailored to common differential diagnostic considerations (Verberk et al.

Longitudinal Trajectories of Blood‐based biomarkers for Alzheimer’s Disease in Subjective Cognitive Decline; the SCIENCe project.

Background: Blood‐based biomarkers are increasingly able to identify Alzheimer’s Disease pathology in the preclinical stages of the disease. These biomarkers hold promise to study development and progression of the disease. Our aim is to investigate the longitudinal trajectories of Aβ ratio, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) in individuals with subjective cognitive decline (SCD).

Experts envision a valuable role for tau‐PET in clinical practice and drug trials.

Background: Recent advancements in Alzheimer’s disease (AD) biomarker research and AD drug trials prompt reflection on the value and appropriate use of tau‐PET in future clinical practice and trials. We therefore conducted a survey among dementia and PET experts worldwide to investigate how they envision the future role of tau‐PET in clinical practice and trials.

Method: An online survey was distributed to dementia clinicians and researchers who were invited to participate through personalized emails, social media channels and/or presentations at relevant conferences.

An atypical clinical phenotype is a risk factor for higher mortality in Alzheimer’s disease.

Background: Survival estimates for individuals with Alzheimer’s disease (AD) are informative to understand the full disease trajectory. A previous meta‐analysis estimated the mean survival of AD patients at 5.8 years from diagnosis, but precise estimates for atypical AD variants are scarce.

Cognitive and physical activity are related to increased cognitive reserve in a large memory clinic cohort.

Background: Cognitive resilience, the ability to maintain cognitive function despite atrophy, is an important area of research in Alzheimer Disease (AD) and other neurodegenerative disorders. Life‐style factors such as participation in cognitively stimulating activity and physical activity are hypothesized to foster neural connections and enhance reserve, consequently sustaining resilience against cognitive loss. Here, we characterize cognitive and physical activity levels in a large memory clinic cohort with multiple etiologies.

Participant recruitment strategies via the Dutch Brain Research Registry: a comparison of effectiveness and efficiency of different strategies for the multi‐domain lifestyle intervention trial FINGER‐NL.

Background: Recruitment of participants for (lifestyle) intervention studies is challenging, especially when targeting cognitively healthy individuals that need to fulfil specific inclusion criteria. We evaluated the effectiveness and efficiency of a participant recruitment campaign from The Dutch Brain Research Registry (DBRR) for the FINGER‐NL study, a multi‐domain lifestyle intervention trial for older adults. Additionally, we explored which recruitment strategy successfully reached individuals from in research under‐represented groups.

Feasibility and acceptability of APOE genotyping in Dutch Brain Research Registry participants.

Background: Participant recruitment for Alzheimer’s disease (AD) research and clinical trials is challenging. Online registries can be used to identify and pre‐screen eligible participants. Additional APOE genotyping has the potential to better identify individuals at‐risk for AD.

Cognitive symptoms and medical history prior to mild cognitive impairment and dementia diagnosis: a retrospective case‐control study using Dutch primary care data.

Background: General practitioners (GPs) play a crucial role in recognizing cognitive deficits and diagnosing dementia. Currently, dementia diagnosis in primary care is prone to be missed or delayed. Electronic health records from GPs can offer insights into the trajectory leading up to a dementia diagnosis.

Differentiating Parkinson‐Plus Syndromes from Other Neurodegenerative Diseases Using Automated T1 MRI Quantification.

Background: Accurate differential diagnosis of neurodegenerative diseases is challenging, but crucial for the management and treatment, particularly given the development of disease‐modifying drug therapies for Alzheimer’s disease (AD). In this work, we investigate imaging biomarkers derived from T1‐weighted magnetic resonance imaging (MRI) with a focus on differentiating Parkinson‐plus syndromes from other relevant diagnostic groups in dementia and Parkinson’s disease (PD).

Method: MR scans from 1206 subjects and three cohorts were used: Parkinson’s Disease Biomarkers Program (PDBP), Amsterdam Dementia Cohort (ADC) and PredictND cohort (PND) (Table 1).

Prognostic value of neuroinflammation [C]PK11195 PET on longitudinal cognitive decline and survival up to 15 years after PET in Alzheimer's disease.

Background: Neuroinflammation plays a key role in Alzheimer’s disease (AD) pathophysiology. However, whether neuroinflammation has a prognostic effect on disease progression is largely unknown. Therefore, we aim to investigate the role of neuroinflammation as measured using PET on longitudinal cognition and survival.

Amyloid‐PET disclosure in Subjective Cognitive Decline: patient experiences and outcomes over time.

Background: Communicating amyloid‐status and the subsequent risk of future cognitive decline to individuals with Subjective Cognitive Decline (SCD) is complex. Insight into how individuals with SCD evaluate the disclosure process and its impact could help optimize current practice. Therefore, the aim of our study was to examine experiences with, and outcomes of, amyloid‐PET disclosure in individuals with SCD over time.

CSF biomarkers trajectories across the AD spectrum reveal the temporal dynamics of amyloid and tau.

Background: The Alzheimer’s disease (AD) research framework proposes a biological definition of the disease. Still, little is known about longitudinal dynamics of core AD biomarker trajectories and how they map to each stage on the clinical spectrum.

Methods: Participants with abnormal amyloid across the cognitive spectrum (i.

Changes in plasma biomarker levels are predictive of amyloid pathology and memory decline in cognitively unimpaired individuals.

Background: Plasma levels of amyloid‐β, and glial fibrillary acidic protein (GFAP) have demonstrated predictive potential for amyloid pathology in the early stages of Alzheimer’s disease (AD) development. Utilizing baseline and up to 6‐year follow‐up plasma, positron emission tomography (PET) and cognitive data from cognitively unimpaired individuals, we here aim to test whether early changes in plasma biomarker levels associate with change in amyloid status and cognitive decline.

Methods: From the EMIF‐AD PreclinAD study we selected individuals with normal cognition and longitudinal plasma, PET and cognitive data available (n=200, table 1).

Distinct CSF proteomic signatures are associated with cognitive decline in A+T+ and A+T‐ individuals with MCI due to Alzheimer’s Disease.

Background: Individuals with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) show variability in cognitive decline. Little is known about the underlying mechanisms, but these are likely to depend on tau levels. Using untargeted proteomics in cerebrospinal fluid (CSF), we studied which processes were associated with cognitive decline in A+T‐ and A+T+ MCI individuals.