ORCID Profile
0000-0002-4061-0837
Current Organisation
University of Agriculture Faisalabad
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Publisher: American Medical Association (AMA)
Date: 09-2019
Publisher: Wiley
Date: 29-04-2019
Publisher: MDPI AG
Date: 13-03-2021
DOI: 10.3390/IJMS22062931
Abstract: Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8 MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001 Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001 Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger s le sets are required.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2020
DOI: 10.1186/S13195-020-00706-2
Abstract: Impairment in daily functioning is a clinical hallmark of dementia. Difficulties with “instrumental activities of daily living” (IADL) seem to increase gradually over the course of Alzheimer’s disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD. In a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 in iduals (mean age 72.5 ± 7.8 years 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants ( n = 982) were classified into the National Institute on Aging–Alzheimer’s Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative in iduals ( n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized. The rate of decline in cognitively normal (stage 1) in iduals with and without abnormal amyloid did not differ ( p = .453). However, from stage 2 onwards, decline was significantly faster in in iduals on the AD continuum ( B [95%CI] = − 0.32 [− 0.55, − 0.09], p = .007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (− 1.06 [− 1.27, − 0.85], p .001) and nearly two SD units per year in stage 4+ (1.93 [− 2.19, − 1.67], p .001). Overall, results were similar between community-based and memory clinic study cohorts. Our results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.
Publisher: Cambridge University Press (CUP)
Date: 13-10-2020
DOI: 10.1017/S1355617720000934
Abstract: Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework. Amyloid-positive in iduals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 in idual neuropsychological tests using linear mixed models. 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For ex le, Category Fluency captured significant 1-year decline as early as Stage 1 ( β = −.58, p .001). Word List Delayed Recall ( β = −.22, p .05) and Trail Making Test ( β = 6.2, p .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 ( β = −1.13, p .001) and 4 ( β = −2.23, p .001). We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
Publisher: Cold Spring Harbor Laboratory
Date: 22-03-2023
DOI: 10.1101/2023.03.21.23287468
Abstract: Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying erse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aβ, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes. - Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions. - The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD. - Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.
Publisher: SAGE Publications
Date: 12-03-2021
Abstract: Providing the right care for each in idual patient is a key element of quality palliative care. Complexity is a relatively new concept, defined as the nature of patients’ situations and the extent of resulting needs. Classifying patients according to the complexity of their care needs can guide integration of services, anticipatory discussions, health service planning, resource management and determination of needs for specialist or general palliative care. However, there is no consistent approach to interpreting and classifying complexity of patient needs. The aim of this article is to identify and describe classification systems for complexity of patient care needs in palliative care. Narrative systematic review (PROSPERO registration number CRD42020182102). MEDLINE, Embase, CINAHL and PsychINFO databases were searched without time limitations. Articles were included that described classification systems for complexity of care requirements in populations with palliative care needs. In total, 4301 records were screened, with nine articles identified reporting the use of patient classification systems in populations with palliative care needs. These articles included the use of six classification systems: HexCom, Perroca Scale, AN-SNAP, Hui Major Criteria, IDC-Pal and PALCOM. These systems were heterogenous in the manner they determined complexity of care needs. The HexCom and IDC-Pal systems contained items that covered all domains of complexity as described by Hodiamont personal, social support, health care team and environment. Although six classification systems have been developed, they access differing aspects of care needs and their application has been limited. The HexCOM and IDC-Pal systems offer the broadest determinations of complexity from an in idual perspective. Further research is needed to apply these systems to populations external to those in which they were developed, and to appreciate how they may integrate with, and impact, clinical care.
Publisher: Informa UK Limited
Date: 27-10-2017
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-10-2020
Abstract: The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). In iduals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system d ens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified in iduals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy in iduals. Together, these studies identify a means by which in iduals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 see also p. 404
Publisher: Oxford University Press (OUP)
Date: 26-11-2022
DOI: 10.1093/BRAINCOMMS/FCAC310
Abstract: Genetic frontotemporal lobar degeneration caused by autosomal dominant gene mutations provides an opportunity for targeted drug development in a highly complex and clinically heterogeneous dementia. These neurodegenerative disorders can affect adults in their middle years, progress quickly relative to other dementias, are uniformly fatal and have no approved disease-modifying treatments. Frontotemporal dementia, caused by mutations in the GRN gene which encodes the protein progranulin, is an active area of interventional drug trials that are testing multiple strategies to restore progranulin protein deficiency. These and other trials are also examining neurofilament light as a potential biomarker of disease activity and disease progression and as a therapeutic endpoint based on the assumption that cerebrospinal fluid and blood neurofilament light levels are a surrogate for neuroaxonal damage. Reports from genetic frontotemporal dementia longitudinal studies indicate that elevated concentrations of blood neurofilament light reflect disease severity and are associated with faster brain atrophy. To better inform patient stratification and treatment response in current and upcoming clinical trials, a more nuanced interpretation of neurofilament light as a biomarker of neurodegeneration is now required, one that takes into account its relationship to other pathophysiological and topographic biomarkers of disease progression from early presymptomatic to later clinically symptomatic stages.
Publisher: Research Square Platform LLC
Date: 07-07-2022
DOI: 10.21203/RS.3.RS-1752559/V2
Abstract: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Plasma GFAP elevations appear a decade before expected symptom onset, after β-amyloid accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished β-amyloid-positive from β-amyloid-negative ADAD participants and showed a stronger relationship with β-amyloid load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. Our findings support a role for plasma GFAP as a clinical biomarker for β-amyloid-associated cognitive deterioration in AD.
Publisher: Wiley
Date: 13-12-2019
Publisher: Elsevier BV
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 11-01-2021
DOI: 10.1038/S41398-020-01137-1
Abstract: Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood s les, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher ( p 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower ( p 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-10-2020
Abstract: The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). In iduals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system d ens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified in iduals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy in iduals. Together, these studies identify a means by which in iduals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 see also p. 404
No related grants have been discovered for Charlotte Teunissen.