Rik Ossenkoppele

Rik Ossenkoppele
Vrije Universiteit Amsterdam | VU · Alzheimer Center VU University MC

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405
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Publications (405)
Article
The advent of PET ligands that bind tau pathology has enabled the quantification and visualization of tau pathology in aging and in Alzheimer disease (AD). There is strong evidence from neuropathologic studies that the most widely used tau PET tracers (i.e., 18F-flortaucipir, 18F-MK6240, 18F-RO948, and 18F-PI2620) bind tau aggregates formed in AD i...
Article
Full-text available
This study investigates the stability of neuropsychiatric symptoms (NPS) assessed biweekly using the Neuropsychiatric Inventory (NPI) in a memory clinic population during a six week period. Twenty‐three spousal caregivers (mean [SD] age=69.7[8.8], 82.6% women) of 23 patients (43.5% had dementia) completed all assessments. The NPI was assessed four...
Article
Background Despite significant symptomatic overlap between behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), a potential overlap in their structural anatomical changes has not been studied systematically. Method In this MRI based meta-analysis, we included studies on bvFTD, schizophrenia, bipolar disorder,...
Preprint
A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer disease (AD) neuropathological hallmarks (i.e., amyloid-beta plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multi-center amyloid and tau PET study (n=132...
Article
Full-text available
Purpose Early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [¹⁸F]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD. Methods Se...
Article
Background Deposition of tau aggregates is a pathological hallmark of Alzheimer's disease that is closely linked both spatially and temporally to emergence of neurodegeneration and manifestation of clinical symptoms. There is an urgent need for accurate PET, CSF, and plasma biomarkers of tau pathology to improve the diagnostic process in clinical p...
Article
Full-text available
Background Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer’s disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. Methods Literature se...
Preprint
Background Repetitive head injury in contact sports is associated with cognitive, neurobehavioral and motor impairments and linked to a unique neurodegenerative disorder: chronic traumatic encephalopathy (CTE). As the clinical presentation is variable, risk factors are heterogenous, and diagnostic biomarkers are not yet established, the diagnostic...
Article
Full-text available
Objective: To investigate relationships of education and intracranial volume (factors related to cognitive versus brain reserve, respectively) with cognitive trajectories and mortality in individuals with biomarker-defined Alzheimer's disease (AD). Methods: We selected 1,298 amyloid-β-positive memory clinic patients with subjective cognitive dec...
Preprint
In Alzheimer's disease (AD), pathologic tau gradually progresses from initially circumscribed predilection regions to closely connected cortical regions. The pattern of tau-deposition is of critical importance for the clinical expression of AD, but the factors that underlie region-dependent susceptibility and resistance to tau pathology remain elus...
Article
Full-text available
Introduction Primary progressive aphasia (PPA) is divided into three prototypical subtypes that are all characterized by their single core symptom of aphasia. Although later in their course, other cognitive, behavioral, and motor domains may become involved, little is known about the progression profile of each subtype relative to the other subtype...
Article
Full-text available
Objective To determine how fully automated Elecsys® CSF immunoassays for β-amyloid (Aβ) and tau biomarkers, and an ultrasensitive Simoa assay for neurofilament light chain (NFL), correlate with neuropathological changes of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods We studied 101 patients with antemortem CSF and...
Article
Alzheimer's disease (AD) is the most frequent cause of dementia in people > 60 years. This white paper summarizes the current standards of AD diagnosis, treatment, care, and prevention. Cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of cerebral amyloidosis and tauopathy allow the diagnosis of AD even before dementia (prod...
Preprint
The behavioral variant of Alzheimer's disease (bvAD) is characterized by early and predominant behavioral changes, resembling the clinical profile of the behavioral variant of frontotemporal dementia (bvFTD). Social cognition deficits form hallmark features in bvFTD and altered biometric responses to socioemotional cues have been observed in bvFTD....
Article
Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design. Objective:...
Article
Full-text available
Background The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric disea...
Article
Tau accumulation starts during the preclinical phase of Alzheimer’s disease and is closely associated with cognitive decline. For preventive purposes, it is important to identify factors associated with tau accumulation and spread. Studying genetically identical twin-pairs may give insight into genetic and environmental contributions to tau patholo...
Preprint
Full-text available
For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer's disease (AD) continuum. In early stages of AD, increased concentration of soluble C...
Article
Full-text available
Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns,...
Article
Full-text available
Importance The behavioral variant of Alzheimer disease (bvAD) is characterized by early and predominant behavioral deficits caused by AD pathology. This AD phenotype is insufficiently understood and lacks standardized clinical criteria, limiting reliability and reproducibility of diagnosis and scientific reporting. Objective To perform a systemati...
Article
Full-text available
Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε...
Article
We have updated our previous amyloid positivity prevalence estimates (Jansen, 2015; Ossenkoppele, 2015; Table 1) with data from 19,097 individuals from 85 cohorts. We tested if prevalence estimates differed for positron emission tomography (PET) or cerebrospinal fluid (CSF) amyloid. We calculated data‐driven CSF cut‐points as previous studies sugge...
Conference Paper
Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD), and have been associated with amyloid‐β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, syna...
Article
to examine the relative role of the frontal cortex in neuropsychiatric symptoms in Alzheimer’s disease (AD), we assessed associations between latent atrophy factors and neuropsychiatric symptoms in AD. We employed a data‐driven Bayesian modelling framework based on Latent Dirichlet Allocation (LDA) to identify latent atrophy factors in a cohort of...
Article
Visual assessment of [18F]flutemetamol amyloid PET images, performed regionally (frontal, lateral temporal, posterior cingulate/precuneus, temporo‐parietal, striatum), is recommended, with a positive (abnormal) classification if any one of these regions is clearly positive. Changes in the striatum, known to contain extensive fibrillar amyloid depos...
Article
The BIN1 rs744373 SNP is a key risk locus for Alzheimer’s disease (AD). Cross‐sectional studies showed BIN1 rs744373 to be associated with higher tau pathology, i.e. a key AD pathological hallmark that is associated with Aβ. Whether carriage of the BIN1 rs744373 risk SNP accelerates the association between Ab and the rate of tau accumulation is unc...
Article
There is currently no consensus on how to optimally define and measure resistance and resilience in aging and Alzheimer´s disease (AD). Residuals from regression analyses can be used to quantify whether an individual´s capacity to avoid (resistance) or cope with (resilience) cerebral damage is higher or lower than expected. We aggregated the rapidl...
Article
Cognitive resilience refers to processes involved in coping with effects of brain pathology on cognition. Factors contributing to cognitive resilience against brain atrophy are unclear, as there have been few longitudinal studies investigating this. Therefore we aimed to identify factors explaining the discrepancy between brain atrophy and longitud...
Conference Paper
Background: Although the majority of individuals with Alzheimer’s disease (AD) dementia exhibit neuropsychiatric symptoms (NPS), there is substantial heterogeneity in NPS manifestation. Sex is increasingly recognized as an important factor in explaining clinical variability within AD; yet, prior studies on sex differences in NPS have reported mixed...
Article
The behavioral variant of frontotemporal dementia (bvFTD) is characterized by marked changes in personality and behaviour. Approximately 30% of cases are genetic in nature and most commonly due to autosomal dominant mutations in the chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN) genes resulting in TAR DNA‐binding protein 43 (TDP...
Article
Quantitative [18F]Flortaucipir (FTP) tau PET analysis has good discriminative accuracy for Alzheimer’s disease (AD), but visual reads are used clinically. We aimed to compare the diagnostic accuracy of FTP‐PET to amyloid PET visual reads for distinguishing AD dementia and amyloid‐positive mild cognitive impairment (MCI) from other neurodegenerative...
Article
Biomarkers for the prediction of cognitive decline in patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD dementia are needed for inclusion of suitable patients in clinical trials. We therefore assessed the ability of tau‐PET, blood and cerebrospinal fluid (CSF) phospho‐Tau217 (pTau217), CSF neurofilament light...
Article
Dynamic [18F]flortaucipir PET imaging allows for more accurate quantification of specific binding compared to static imaging in Alzheimer’s disease (AD). Besides, with dynamic imaging flow is taken into account, which is especially important in longitudinal studies, because disease progression or drug intervention may lead to flow changes. We aimed...
Article
Tau accumulation starts during the preclinical phase of Alzheimer’s disease (AD) and is closely associated with cognitive decline. For preventive purposes, it is important to identify factors associated with tau accumulation and spread. Studying genetically identical twin‐pairs may give insight into genetic and environmental contributions to tau ac...
Article
Tau PET tracers have proven useful for diagnostic purposes, but their prognostic utility for predicting future cognitive changes over time is unclear. We aimed to examine the prognostic accuracy of [18F]flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer’s disease (AD) spectrum. We included 673 cognitively unimpaired individua...
Article
Background: To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer's disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia. Method: We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([18 F]florbetapir or [18 F]florbetaben) and ta...
Article
The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging informat...
Preprint
Full-text available
Background: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo Neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric dise...
Preprint
Full-text available
Importance: The behavioral variant of Alzheimer disease (bvAD) is characterized by early and predominant behavioral deficits caused by AD pathology. This AD phenotype is insufficiently understood and lacks standardized clinical criteria, limiting reliability and reproducibility of diagnosis and scientific reporting. Objective: To perform a systemat...
Preprint
Full-text available
Purpose: Semi-quantitative PET measures can be affected by changes in blood flow, whereas quantitative measures are not. The aim of the study was to compare semi-quantitative(SUVr) and quantitative(R1, BPND) parameters of longitudinal tau PET scans with [18F]flortaucipir, with respect to changes in blood flow. Methods: Subjects with subjective cogn...
Preprint
Full-text available
Purpose. Early-onset Alzheimer′ s disease (EOAD) and late-onset Alzheimer′ s disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [18F]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD. Methods....
Article
Full-text available
Objective To investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid- β positive individuals across the Alzheimer’s disease (AD) clinical spectrum. Methods In this single-center observational study, we included all individuals who visited the Alzheimer Center Amster...
Article
Full-text available
Background Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau patho...
Article
Objective There is currently a lack of consensus on how to optimally define and measure resistance and resilience in brain and cognitive aging. Residual methods use residuals from regression analysis to quantify the capacity to avoid (resistance) or cope (resilience) “better or worse than expected” given a certain level of risk or cerebral damage....
Article
Full-text available
PET, CSF and plasma biomarkers of tau pathology may be differentially associated with Alzheimer's disease (AD)-related demographic, cognitive, genetic and neuroimaging markers. We examined 771 participants with normal cognition, mild cognitive impairment or dementia from BioFINDER-2 (n = 400) and ADNI (n = 371). All had tau-PET ([18 F]RO948 in BioF...
Article
Full-text available
Purpose A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which dem...
Article
Full-text available
Purpose To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [¹⁸F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods We included 351 subjects with varying clinical diagnoses from three cohorts...
Article
Full-text available
Purpose To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer’s disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia. Methods We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([ ¹⁸ F]florbetapir or [ ¹⁸ F]florbetaben) and tau ([...
Article
Full-text available
Purpose In 2017, the Geneva Alzheimer’s disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [¹⁸F]flortaucipir PET and define i...
Article
Full-text available
Purpose In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into th...
Article
Full-text available
Purpose In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer’s disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers—encompassing the 42 a...
Article
Full-text available
Purpose The development of blood biomarkers that reflect Alzheimer’s disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomark...
Article
Full-text available
Background The 2017 Alzheimer’s disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1–2), clinical validity (Phases 3–4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps...
Article
Full-text available
Purpose The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implem...
Article
Full-text available
Purpose This study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [ ¹⁸ F]flortaucipir, [ ¹⁸ F]RO948, and [ ¹⁸ F]MK6240 tau positron emission tomography (PET) tracers for differential diagnosis of Alzheimer’s disease (AD) dementia vs either cognitively unimpaired (CU) individuals or non-AD neur...
Article
Full-text available
Objective To assess the [ ¹⁸ F]flortaucipir binding distribution across MAPT mutations in presymptomatic and symptomatic carriers. Methods We compared regional [ ¹⁸ F]flortaucipir binding potential(BP ND ) derived from a 130-minute dynamic [ ¹⁸ F]flortaucipir PET scan, in nine (pre)symptomatic MAPT mutation carriers(4 with P301L[1 symptomatic], 2...
Article
Importance Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective To examine the prognostic accuracy of baseline fluorine 18 (¹⁸F)–flortaucipir and [¹⁸F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clin...
Article
Full-text available
Introduction: The BIN1 rs744373 single nucleotide polymorphism (SNP) is a key genetic risk locus for Alzheimer's disease (AD) associated with tau pathology. Because tau typically accumulates in response to amyloid beta (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-related tau accumulation. Methods: We included two samples (Alzheimer's Dis...
Article
Full-text available
Disentangling biologically distinct subgroups of Alzheimer’s disease (AD) may facilitate a deeper understanding of the neurobiology underlying clinical heterogeneity. We employed longitudinal [18F]FDG-PET standardized uptake value ratios (SUVRs) to map hypometabolism across cognitively-defined AD subgroups. Participants were 384 amyloid-positive in...
Article
The recent development of several tau positron emission tomography (PET) tracers represents a major milestone for the Alzheimer's disease (AD) field. These tau PET tracers bind tau neurofibrillary tangles, a key neuropathological characteristic of AD that is tightly linked to synaptic loss, brain atrophy, and cognitive decline. It is notable that t...
Article
Full-text available
Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we ident...