- University of Antwerp, Biomedical Sciences, Faculty Memberadd
Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains... more
Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively a...
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Alzheimer’s disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1–42), total tau protein (T-tau), and tau protein phosphorylated at threonine 181 (P-tau181) are considered surrogate biomarkers of Alzheimer’s disease pathology,... more
Alzheimer’s disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1–42), total tau protein (T-tau), and tau protein phosphorylated at threonine 181 (P-tau181) are considered surrogate biomarkers of Alzheimer’s disease pathology, and significantly improve diagnostic accuracy. Their ability to reflect neuropathological changes later in the disease course is not well characterized. This study aimed to assess the potential of CSF biomarkers measured in mid to late stage Alzheimer’s disease to reflect post-mortem neuropathological changes. Individuals were selected from two autopsy cohorts of Alzheimer’s disease patients in Antwerp and Amsterdam. Neuropathological diagnosis was performed according to the updated consensus National Institute on Aging-Alzheimer’s Association guidelines, which includes quantification of amyloid-β plaque, neurofibrillary tangle, and neuritic plaque load. CSF samples were analysed for Aβ1–42, T-tau, and P-tau181 by ELISA. One hundred and fourteen cas...
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Background: physiological differences between males and females could contribute to the development of Alzheimer’s Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored... more
Background: physiological differences between males and females could contribute to the development of Alzheimer’s Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites’ discriminatory performance in AD. Results: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). K...
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We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes.... more
We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes. CSF levels of routine AD biomarkers (phosphorylated tau (p-tau), total tau (t-tau), and amyloid-beta (Aβ)) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20). FTLD subgroups were defined by genetic carrier status and/or postmortem neuropathological confirmation (FTLD-TDP: n = 34, including FTLD-C9orf72: n = 19 and FTLD-GRN: n = 9; FTLD-tau: n = 10). GRN mutation carriers had significantly lower progranulin levels compared to other FTLD patients, AD, and controls. Both t-tau and p-tau were normal in FTLD patients, even in FTLD-tau. Aβ levels were very variable in FTLD. Neurofilament light chain (Nf-L) was significantl...
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Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients.... more
Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p.Pro96Thr) that were also present in the matched control series. In TUBA4A, we detected a novel frameshift mutation (p.Arg64Glyfs*90) leading to a truncated protein in 1 FTD patient (1/459 of 0.22%) with family history of Parkinson's disease and cognitive impairment, and a novel missense mutation (p.Thr381Met) in 2 sibs with familial ALS and memory problems (1 index patient/429, 0.23%) in whom we previously identified a pathogenic Chromosome 9 open reading frame...
Research Interests: Genetics, Dementia, Biology, Medicine, Belgium, and 15 moreAmyotrophic Lateral Sclerosis, Humans, Mutation, Female, Male, Genetic Association Studies, Clinical Sciences, Aged, Middle Aged, Frontotemporal Dementia, Neurobiology of Aging, HUMAN MEDICINE, Cohort Studies, Mitochondrial Proteins, and frameshift mutation
Research Interests: Cognitive Science, Dementia, Biomarkers, Medicine, Cerebrospinal Fluid, and 15 moreHumans, Female, Animals, Epitope mapping, Male, Phosphorylation, Clinical Sciences, Aged, Biomarker, Alzheimer Disease, Neurosciences, Enzyme Linked Immunosorbent Assay, HUMAN MEDICINE, immunoglobulin G, and Cognitive dysfunction
Dipeptidyl peptidase IV (DPPIV) inhibition may be a promising therapeutic strategy for acute stroke treatment, given its potential to prolong the biological half-life of neuroprotective substrates. A related protease, fibroblast... more
Dipeptidyl peptidase IV (DPPIV) inhibition may be a promising therapeutic strategy for acute stroke treatment, given its potential to prolong the biological half-life of neuroprotective substrates. A related protease, fibroblast activation protein (FAP), was recently shown to inactivate the same substrates. Therefore, it should also be investigated as a potential target in stroke. The study aimed to investigate whether stroke severity and outcome correlate with DPPIV and FAP activities and their kinetics shortly after acute ischemic stroke. DPPIV and FAP activities were analyzed in the serum of 50 hyperacute stroke patients at admission, 1 day, 3 days, and 7 days after stroke onset and in 50 age-matched healthy controls. This was done as part of the Middelheim's Interdisciplinary Stroke Study. DPPIV activity tended to increase shortly after stroke compared to the control population. DPPIV and FAP activities steadily decreased in the first week after stroke onset. Higher infarct ...
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Research Interests: Psychology, Cognitive Science, Dementia, Medicine, Cerebrospinal Fluid, and 15 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Aged, Biomarker, Age Factors, Cognitive Decline, Alzheimer Disease, Neurosciences, Enzyme Linked Immunosorbent Assay, Area Under Curve, Cognitive dysfunction, and Tau proteins
MicroRNAs (miRNAs) regulate translational inhibition of proteins, but are also detected in body fluids, including cerebrospinal fluid (CSF), where they may serve as disease-specific biomarkers. Previously, we showed differential... more
MicroRNAs (miRNAs) regulate translational inhibition of proteins, but are also detected in body fluids, including cerebrospinal fluid (CSF), where they may serve as disease-specific biomarkers. Previously, we showed differential expression of miR-146a, miR-29a, and miR-125b in the CSF of Alzheimer's disease (AD) patients versus controls. In this study, we aim to confirm these findings by using larger, independent sample cohorts of AD patients and controls from three different centers. Furthermore, we aim to identify confounding factors that possibly arise using such a multicenter approach. The study was extended by including patients diagnosed with mild cognitive impairment due to AD, frontotemporal dementia and dementia with Lewy bodies. Previous results of decreased miR-146a levels in AD patients compared to controls were confirmed in one center. When samples from all three centers were combined, several confounding factors were identified. After controlling for these factors,...
Research Interests: Cognitive Science, Dementia, MicroRNA, Biomarkers, Medicine, and 15 moreCerebrospinal Fluid, Humans, Female, Male, Clinical Sciences, Aged, Middle Aged, microRNAs, Frontotemporal Dementia, Disease Progression, Alzheimer Disease, Neurosciences, HUMAN MEDICINE, Case Control Studies, and Cognitive dysfunction
Cerebrospinal fluid (CSF) amyloid-beta (Aβ) peptides are predictive biomarkers for Alzheimer's disease and are proposed as pharmacodynamic markers for amyloid-lowering therapies. However, frequent sampling results in fluctuating CSF... more
Cerebrospinal fluid (CSF) amyloid-beta (Aβ) peptides are predictive biomarkers for Alzheimer's disease and are proposed as pharmacodynamic markers for amyloid-lowering therapies. However, frequent sampling results in fluctuating CSF Aβ levels that have a tendency to increase compared with baseline. The impact of sampling frequency, volume, catheterization procedure, and ibuprofen pretreatment on CSF Aβ levels using continuous sampling over 36 h was assessed. In this open-label biomarker study, healthy participants (n = 18; either sex, age 55 - 85 years) were randomized into one of three cohorts (n = 6/cohort; high-frequency sampling). In all cohorts except cohort 2 (sampling started 6 h post catheterization), sampling through lumbar catheterization started immediately post catheterization. Cohort 3 received ibuprofen (800 mg) before catheterization. Following interim data review, an additional cohort 4 (n = 6) with an optimized sampling scheme (low-frequency and lower volume) wa...
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To generate a clinical and pathologic phenotype of patients carrying rare loss-of-function mutations in ABCA7, identified in a Belgian Alzheimer patient cohort and in an autosomal dominant family. We performed a retrospective review of... more
To generate a clinical and pathologic phenotype of patients carrying rare loss-of-function mutations in ABCA7, identified in a Belgian Alzheimer patient cohort and in an autosomal dominant family. We performed a retrospective review of available data records, medical records, results of CSF analyses and neuroimaging studies, and neuropathology data. The mean onset age of the mutation carriers (n = 22) was 73.4 ± 8.4 years with a wide age range of 36 (54-90) years, which was independent of APOE genotype and cerebrovascular disease. The mean disease duration was 5.7 ± 3.0 years (range 2-12 years). A positive family history was recorded for 10 carriers (45.5%). All patient carriers except one presented with memory complaints. The 4 autopsied brains showed typical immunohistochemical changes of late-onset Alzheimer disease. All patients carrying a loss-of-function mutation in ABCA7 exhibited a classical Alzheimer disease phenotype, though with a striking wide onset age range, suggesting...
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This case report describes an 85 year-old woman who underwent a bilateral frontal lobotomy for presumed schizophrenia 50 years ago. The patient presented with sudden alterations of consciousness accompanied by motionless staring and... more
This case report describes an 85 year-old woman who underwent a bilateral frontal lobotomy for presumed schizophrenia 50 years ago. The patient presented with sudden alterations of consciousness accompanied by motionless staring and speech and movement arrest. After 5 to 10 seconds, contact recovered briskly. As there was electrophysiological evidence for a frontal epileptic focus, these fits were classified as complex partial frontal lobe seizures with impairment of consciousness at onset. An aetiological link with the bifrontal lobotomy is probable. At the occasion of this case report, complications of frontal lobotomy are reviewed.
Research Interests: Schizophrenia, Medicine, Humans, Female, Pubmed, and 6 moreClinical Sciences, Aged, Lobotomy, Psychosurgery, Neurosciences, and Frontal Lobe
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We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2538 patients with FTD, ALS or FTD plus ALS, ascertained within the... more
We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2538 patients with FTD, ALS or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein truncating mutations led to loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three time...
Research Interests: Genetics, Biology, Amyotrophic Lateral Sclerosis, Humans, ALS, and 15 moreFemale, Disease, Genetic Association Studies, Clinical Sciences, Aged, Frontotemporal Dementia, European Continental Ancestry Group, FTD, Amino Acid Substitution Rates, HUMAN MEDICINE, Case Control Studies, Cohort Studies, Diagnostic Criteria, Human mutation, and alleles
Multiple sclerosis (MS) is an autoimmune disorder of the CNS. Different subtypes of the disease have been noted, and characterized by distinct clinical courses and histopathologic manifestations. The most intensively studied animal model... more
Multiple sclerosis (MS) is an autoimmune disorder of the CNS. Different subtypes of the disease have been noted, and characterized by distinct clinical courses and histopathologic manifestations. The most intensively studied animal model of MS, experimental autoimmune encephalomyelitis (EAE), classically leads to deficits in motor functions, and is mediated by T helper cells. Recently, T(H)17 cells were ascribed an even greater pathogenic impact than T(H)1 cells, but new findings render this view controversial. Although classic EAE has been an invaluable tool, it does not cover the entire pathogenic entity of MS. Especially B-cell contribution and autoantibody-dependence are not mirrored adequately: therefore, new B-cell-dependent models, such as MP4-induced EAE, have been introduced. Furthermore, certain symptoms and the spontaneous onset of MS are not featured in classic EAE. Herein, atypical and spontaneous EAE models can be used for investigation of common symptoms, such as tremor and ataxia, as well as spontaneous disease development. MS displays a marked inter-individual heterogeneity, and no single model will be able to cover all features. Thus, depending on the objective of one's study, the appropriate EAE model has to be carefully chosen. In addition, refined models should be designed to gain a more complete understanding of MS.
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Background: Distinguishing between Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) results in poor diagnostic accuracy. Objective: To investigate the utility of electroencephalography (EEG)-based biomarkers in... more
Background: Distinguishing between Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) results in poor diagnostic accuracy. Objective: To investigate the utility of electroencephalography (EEG)-based biomarkers in comparison and in addition to established cerebrospinal fluid (CSF) biomarkers in the AD versus FTLD differential diagnosis. Methods: The study cohort comprised 37 AD and 30 FTLD patients, of which 17 AD and 9 FTLD patients had definite diagnoses. All participants had CSF neurochemical (NCM) biomarker analyses (Aβ1-42, T-tau, P-tau181, and Nf-L) and underwent 19-channel resting-state EEG. From the EEG spectra, dominant frequency peaks were extracted in four regions resulting in four dominant frequencies. This produced eight features (4 NCM + 4 EEG). Results: When NCM and EEG markers were combined, the diagnostic accuracy increased significantly. In the whole group, the accuracy went up from 79% (NCM) to almost 82%, while in the definite group only, it wen...
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In this article, we explore if the observation of writing behavior can assist in the screening and follow-up of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). To this end, we examined the extent to... more
In this article, we explore if the observation of writing behavior can assist in the screening and follow-up of mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). To this end, we examined the extent to which overall writing process measures and pausing behavior during writing differed between 15 cognitively impaired patients and 15 age- and gender-matched healthy controls. Participants completed two typed picture description tasks that were registered with Inputlog, a keystroke logging program that captures keyboard activity during text production. The following variables were analyzed with mixed-effects models: time on task; number of characters, pauses and Pause-bursts per minute; proportion of pause time; duration of Pause-bursts; and pause time between words. For pause time between words, also the effect of pauses preceding specific word categories was analyzed. Results showed a main effect of group on all variables. In addition, for pause time be...
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Introduction: Distinguishing between two of the most common causes of dementia, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD), on clinical diagnostic criteria alone has poor diagnostic accuracy. Promising tools to... more
Introduction: Distinguishing between two of the most common causes of dementia, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD), on clinical diagnostic criteria alone has poor diagnostic accuracy. Promising tools to increase the diagnostic accuracy of AD are the use of cerebrospinal fluid (CSF) biomarkers and electroencephalography (EEG), which is being investigated as a diagnostic tool for neurodegenerative brain disorders. In this study, we investigated the utility of EEG-based biomarkers in comparison and in addition to established neurochemical biomarkers in the AD versus FTLD differential diagnosis. Methods: Our study cohort comprised 37 AD and 32 FTLD patients, of which 19 AD and 11 FTLD had definite diagnoses. All these participants had CSF biomarker analyses resulting in four neurochemical (NCM) biomarkers (Aβ1-42, T-tau, P-tau181 and Nf-L) and underwent 19-channel resting-state EEG. From the EEG spectra, dominant frequency peaks (DFP) were extracted in f...
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Research Interests: Management, Cognitive Science, Depression, Belgium, Activities of Daily Living, and 15 moreHumans, Female, Male, Depressive Disorder, Follow Up, Interpersonal Relations, Incidence, Clinical Sciences, Geriatric Psychiatry, Aged, Longitudinal Studies, Adult, Functional Recovery, HUMAN MEDICINE, and Cerebral Infarction
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internationally accepted criteria, and AD cases were further classified for the presence of cerebrovascular disease (CBVD). Controls with no history of stroke and cognitive impairment were selected from the Singapore Epidemiology of Eye... more
internationally accepted criteria, and AD cases were further classified for the presence of cerebrovascular disease (CBVD). Controls with no history of stroke and cognitive impairment were selected from the Singapore Epidemiology of Eye Disease program and matched by race, gender and 5year age groups. Retinal vascular parameters (retinal vascular caliber, fractal dimension and tortuosity) were assessed using a semi-automated computer-based program. Due to its skewed distribution, retinal vessel tortuosity was log-transformed. Logistic regression models were constructed adjusting for gender, age, hypertension, diabetes and hypercholesterolemia status. Results: A total of 156 AD cases (98 without CBVD and 58with CBVD), 27 vascular dementia cases, and 493 controls were included in this preliminary analysis. Narrower arteriolar caliber was associated with VaD (multivariable-adjusted odds ratio (OR) per standard deviation (SD) decrease: 2.41; 95%CI: 1.13-5.14) and AD with CBVD (OR per SD decrease: 1.84; 95%CI: 1.05-3.23). Narrower venular caliber (OR per SD decrease: 1.72; 95%CI: 1.11-2.68), decreased arteriolar fractal dimension (OR per SD decrease: 1.29; 95%CI: 1.03-1.61) and venular fractal dimension (OR per SD increase: 1.36; 95%CI: 1.08-1.72) were associated with only AD without CBVD. However, increased arteriolar and venular tortuosity was associated with all three subtypes of dementia. Conclusions: A sparser retinal microvascular network was associated with AD, whereas narrower arterioles were associated with dementia linked to CBVD, and tortuous retinal vessels were associated with all three subtypes of dementia. This suggests that retinal vascular parameters may potentially useful in assessing the contribution of microvascular pathology to the different subtpyes of dementia.
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Research Interests: Chemistry, Biology, Medicine, Western blotting, Dimensional Analysis, and 14 moreCerebrospinal Fluid, Humans, Cholesterol, Animals, Astrocyte, Rats, Analytical Ultracentrifugation, Lipoproteins, Lipid, Enzymatic Activity, Alzheimer Disease, Biochemistry and cell biology, Case Control Studies, and Medical biochemistry and metabolomics
Although brain atrophy is considered to be a downstream marker of Alzheimer's disease (AD), subtle changes may allow to identify healthy subjects at risk of developing AD. As the ability to select at-risk persons is considered to be... more
Although brain atrophy is considered to be a downstream marker of Alzheimer's disease (AD), subtle changes may allow to identify healthy subjects at risk of developing AD. As the ability to select at-risk persons is considered to be important to assess the efficacy of drugs and as MRI is a widely available imaging technique we have recently developed a reliable segmentation algorithm for the corpus callosum (CC). Callosal atrophy within AD has been hypothesized to reflect both myelin breakdown and Wallerian degeneration. We applied our fully automated segmentation and feature extraction algorithm to two datasets: the OASIS database consisting of 316 healthy controls (HC) and 100 patients affected by either mild cognitive impairment (MCI) or Alzheimer's disease dementia (ADD) and a second database that was collected at the Memory Clinic of Hospital Network Antwerp and consists of 181 subjects, including healthy controls, subjects with subjective cognitive decline (SCD), MCI, ...
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The debate on frailty in later life focuses primarily on deficits and their associations with adverse (health) outcomes. In addition to deficits, it may also be important to consider the abilities and resources of older adults. This study... more
The debate on frailty in later life focuses primarily on deficits and their associations with adverse (health) outcomes. In addition to deficits, it may also be important to consider the abilities and resources of older adults. This study was designed to gain insights into the lived experiences of frailty among older adults to determine which strengths can balance the deficits that affect frailty. Data from 121 potentially frail community-dwelling older adults in Flemish-speaking Region of Belgium and Brussels were collected using a mixed-methods approach. Quantitative data were collected using the Comprehensive Frailty Assessment Instrument (CFAI), Montreal Cognitive Assessment (MoCA), and numeric rating scales (NRS) for quality of life (QoL), care and support, meaning in life, and mastery. Bivariate analyses, paired samples t-tests and means were performed. Qualitative data on experiences of frailty, frailty balance, QoL, care and support, meaning in life, and mastery were collect...
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Analyses of cerebrospinal fluid (CSF) biomarkers (β-amyloid protein, total tau protein, and hyperphosphorylated tau protein) are part of the diagnostic criteria of Alzheimer disease. Different preanalytical sample procedures contribute to... more
Analyses of cerebrospinal fluid (CSF) biomarkers (β-amyloid protein, total tau protein, and hyperphosphorylated tau protein) are part of the diagnostic criteria of Alzheimer disease. Different preanalytical sample procedures contribute to variability of CSF biomarker concentrations, hampering between-laboratory comparisons. The aim of this study was to explore the influence of fractionated sampling, centrifugation, freezing temperature, freezing delay, and freeze-thaw cycles on CSF biomarker analyses. We studied fractionated sampling in sequential aliquots of lumbar CSF. Centrifuged and noncentrifuged samples from the same fraction were compared. CSF samples were subjected to different protocols (liquid nitrogen, -80 °C, and -20 °C; 24 h at 2-8 °C; and 24 and 48 h at room temperature). To study the influence of freeze-thaw cycles, samples were thawed up to 4 times and refrozen at -80 °C. CSF was collected in polypropylene tubes. We measured CSF biomarker concentrations with commerci...
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Combined analysis of the Alzheimer's disease (AD) biomarkers amyloid-β(1-42) (Aβ(1-42)), total tau (T-tau), and hyperphosphorylated tau (P-tau(181P)) in cerebrospinal fluid (CSF) reduces the uncertainty associated with clinical... more
Combined analysis of the Alzheimer's disease (AD) biomarkers amyloid-β(1-42) (Aβ(1-42)), total tau (T-tau), and hyperphosphorylated tau (P-tau(181P)) in cerebrospinal fluid (CSF) reduces the uncertainty associated with clinical dementia diagnosis. The present study evaluated the diagnostic accuracy of the CSF biomarker concentrations obtained with a multi-analyte Luminex assay (INNO-BIA AlzBio3) in comparison to single-analyte ELISA tests (INNOTEST). Data from 66 pathologically-confirmed dementia patients (51 AD and 15 non-AD) and 95 controls were included. Cut-off values were determined for each individual biomarker determined using both methods for different diagnostic challenges (dementia-controls; AD-controls; AD-non-AD). Comparing the diagnostic accuracy of individual cut-off values between INNO-BIA and INNOTEST, no relevant differences could be identified. Logistic regression was used in addition to identify the best combination of predictor variables (biomarkers). Discrim...
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Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy has shown the potential to discriminate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, these studies did not reflect clinical practice, as... more
Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy has shown the potential to discriminate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, these studies did not reflect clinical practice, as patients with ischemic heart disease, heart failure, diabetes mellitus, arterial hypertension, and hyperlipidemia and patients treated with antidepressants like trazodone were excluded. This study aimed to evaluate the use of MIBG cardiac scintigraphy to diagnose DLB in clinical practice. Moreover, the potential diagnostic value of MIBG cardiac scintigraphy in patients with clinically ambiguous dementia diagnosis (DLB versus AD) was tested. Eighty-five patients with a possible clinical diagnosis of DLB entered the study. MIBG uptake was determined by calculating the heart-to-mediastinum-uptake ratio (H/M). The average H/M ratio was 1.42 ± 0.35. The number of core features for DLB and the H/M ratio were negatively correlated (p = 0.001; r = -0.360). With an...
Research Interests: Cognitive Science, Dementia, Biomarkers, Medicine, Humans, and 15 moreBodies, Female, Diagnosis, Male, Differential Diagnosis, Clinical Sciences, Geriatric Psychiatry, Aged, Middle Aged, Alzheimer Dementia, Lewy Body Dementia, Alzheimers Disease, Alzheimer Disease, Dementia With Lewy Bodies, and HUMAN MEDICINE
Behavioral disturbances belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). The identification of sets of symptoms is clinically interesting, as interventions targeting syndromes may be more... more
Behavioral disturbances belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). The identification of sets of symptoms is clinically interesting, as interventions targeting syndromes may be more effective than the management of individual symptoms. This study aimed to identify, describe, measure, and compare the fundamental behavioral syndromes that underlie the observed behavioral symptoms in MCI and Alzheimer's disease (AD). A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms in MCI and dementia was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI), and Cornell Scale for Depression in Dementia (CSDD). Principal components factor analysis with Direct Oblimin rotation was carried out on the MFS score ≥5, seven cluster scores of ...
Research Interests: Cognitive Science, Principal Component Analysis, Mild Cognitive Impairment, Medicine, Humans, and 15 moreFemale, Disease, Male, Behavioral Disorders, Clinical Sciences, BPSD, Aged, Middle Aged, Longitudinal Studies, Alzheimer Dementia, Cross Sectional Studies, Alzheimer Disease, Neurosciences, Behavioral symptoms, and Neuropsychological Tests
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Research Interests: Medicine, Humans, Headache, Lancet, Fever, and 3 moreElsevier, The Lancet, and Medical and Health Sciences
A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further... more
A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, while the second, ADx215, detects an epitope formed by the Tau N-terminus when Tau is not phosphorylated at Tyr18. For the third antibody, ADx210, the binding site could not be determined since its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low-order Tau oligomers in diseased brai...