Author
Bart N.M. van Berckel
Other affiliations: VU University Medical Center, Utrecht University, Columbia University ...read more
Bio: Bart N.M. van Berckel is an academic researcher from VU University Amsterdam. The author has contributed to research in topics: Dementia & Medicine. The author has an hindex of 57, co-authored 282 publications receiving 10176 citations. Previous affiliations of Bart N.M. van Berckel include VU University Medical Center & Utrecht University.
Topics: Dementia, Medicine, Cognitive decline, Alzheimer's disease, Cognition
Papers published on a yearly basis
Papers
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TL;DR: Activated microglia are present in schizophrenia patients within the first 5 years of disease onset, which suggests that, in this period, neuronal injury is present and that neuronal damage may be involved in the loss of gray matter associated with this disease.
529 citations
VU University Medical Center1, Maastricht University2, University of California, Berkeley3, Helen Wills Neuroscience Institute4, University of California, San Francisco5, Seoul National University6, Sungkyunkwan University7, Paris Descartes University8, Washington University in St. Louis9, Leipzig University10, Neuroscience Research Australia11, Katholieke Universiteit Leuven12, University of Cologne13, Technische Universität München14, University of Cantabria15, The Chinese University of Hong Kong16, François Rabelais University17, University of Pittsburgh18, Thomas Jefferson University19, University of Copenhagen20, Avid Radiopharmaceuticals21, University of Pennsylvania22, Karolinska Institutet23, Turku University Hospital24, French Institute of Health and Medical Research25, Autonomous University of Barcelona26, Copenhagen University Hospital27, University of Texas at Dallas28, University of Texas Southwestern Medical Center29
TL;DR: Findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status.
Abstract: Importance Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non–AD dementia. Objective To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes. Data Sources The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies. Study Selection Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data. Data Extraction and Synthesis Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non–AD dementia. The reference groups were 1849 healthy control participants (with amyloid PET) and an independent sample of 1369 AD participants (with autopsy data). Main Outcomes and Measures Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) e4 status, using the generalized estimating equations method. Results The likelihood of amyloid positivity was associated with age and APOE e4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE e4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE e4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P Conclusions and Relevance Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE e4 status who are older than 70 years.
479 citations
TL;DR: Behavioural Alzheimer's disease presentations are characterized by a milder and more restricted behavioural profile than in behavioural variant frontotemporal dementia, co-occurrence of memory dysfunction and high APOE ε4 prevalence.
Abstract: A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE e4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59), and controls (n = 61). Patients with behavioural Alzheimer's disease showed worse memory scores than behavioural variant frontotemporal dementia and did not differ from typical Alzheimer's disease, while executive function composite scores were lower compared to behavioural variant frontotemporal dementia and typical Alzheimer's disease. Voxel-wise contrasts between behavioural and dysexecutive Alzheimer's disease patients and controls revealed marked atrophy in bilateral temporoparietal regions and only limited atrophy in the frontal cortex. In direct comparison with behavioural and those with dysexecutive Alzheimer's disease, patients with behavioural variant frontotemporal dementia showed more frontal atrophy and less posterior involvement, whereas patients with typical Alzheimer's disease were slightly more affected posteriorly and showed less frontal atrophy (P < 0.001 uncorrected). Among 24 autopsied behavioural Alzheimer's disease/dysexecutive Alzheimer's disease patients, only two had primary co-morbid FTD-spectrum pathology (progressive supranuclear palsy). In conclusion, behavioural Alzheimer's disease presentations are characterized by a milder and more restricted behavioural profile than in behavioural variant frontotemporal dementia, co-occurrence of memory dysfunction and high APOE e4 prevalence. Dysexecutive Alzheimer's disease presented as a primarily cognitive phenotype with minimal behavioural abnormalities and intermediate APOE e4 prevalence. Both behavioural Alzheimer's disease and dysexecutive Alzheimer's disease presentations are distinguished by temporoparietal-predominant atrophy. Based on the relative sparing of frontal grey matter, we propose to redefine these clinical syndromes as 'the behavioural/dysexecutive variant of Alzheimer's disease' rather than frontal variant Alzheimer's disease. Further work is needed to determine whether behavioural and dysexecutive-predominant presentations of Alzheimer's disease represent distinct phenotypes or a single continuum.
393 citations
TL;DR: It is shown that Δ9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, induces dopamine release in the human striatum, implying that the endogenous cannabinoid system is involved in regulating striatal dopamine release.
350 citations
TL;DR: Clinical relevant decreased FC within the default-mode network (DMN) in the precuneus and posterior cingulate cortex compared with controls was observed in Alzheimer's disease.
331 citations
Cited by
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Mayo Clinic1, Rush University2, University of Gothenburg3, Alzheimer's Association4, Silver Spring Networks5, Biogen Idec6, Washington University in St. Louis7, University of California, Berkeley8, University of Cologne9, University of Pennsylvania10, Stanford University11, National Institutes of Health12, University of California, San Francisco13, University of Melbourne14, VU University Medical Center15, Eli Lilly and Company16, Brigham and Women's Hospital17
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
Abstract: In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
5,126 citations
TL;DR: This work proposes a model that relates disease stage to AD biomarkers in which Abeta biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegnerative biomarker become abnormal later, and correlate with clinical symptom severity.
Abstract: Summary Currently available evidence strongly supports the position that the initiating event in Alzheimer's disease (AD) is related to abnormal processing of β-amyloid (Aβ) peptide, ultimately leading to formation of Aβ plaques in the brain. This process occurs while individuals are still cognitively normal. Biomarkers of brain β-amyloidosis are reductions in CSF Aβ 42 and increased amyloid PET tracer retention. After a lag period, which varies from patient to patient, neuronal dysfunction and neurodegeneration become the dominant pathological processes. Biomarkers of neuronal injury and neurodegeneration are increased CSF tau and structural MRI measures of cerebral atrophy. Neurodegeneration is accompanied by synaptic dysfunction, which is indicated by decreased fluorodeoxyglucose uptake on PET. We propose a model that relates disease stage to AD biomarkers in which Aβ biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity.
3,953 citations
University Hospital Bonn1, University of California, Riverside2, Harvard University3, Case Western Reserve University4, University of Illinois at Chicago5, European Institute6, VA Palo Alto Healthcare System7, Stanford University8, Spanish National Research Council9, Cleveland Clinic Lerner Research Institute10, Hong Kong University of Science and Technology11, University of California, Los Angeles12, University of Southern Denmark13, University of Cambridge14, University of Manchester15, Ikerbasque16, University of the Basque Country17, RIKEN Brain Science Institute18, University of Eastern Finland19, University of Bonn20, University of Massachusetts Medical School21, Center of Advanced European Studies and Research22, University of Southern California23, University of South Florida24, Duke University25, Southampton General Hospital26, Moorgreen Hospital27, University of Southampton28, Louisiana State University29, Imperial College London30, Centre national de la recherche scientifique31, Karolinska Institutet32, Max Planck Society33, University of Tübingen34, University of Groningen35, University of Colorado Denver36, Douglas Mental Health University Institute37
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
3,947 citations
University College London1, Camden and Islington NHS Foundation Trust2, King's College London3, University of Melbourne4, University of Exeter5, Brighton and Sussex Medical School6, University of Manchester7, Tel Aviv University8, Johns Hopkins University9, University of Michigan10, Kaiser Permanente11, University of Washington12, University of Edinburgh13, University of Montpellier14, Dalhousie University15, University of Southern California16, Innlandet Hospital Trust17, University of Oslo18
TL;DR: The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what the authors should do to prevent and manage dementia.
3,826 citations