1,720,962 research outputs found
ADCOMS sensitivity versus baseline diagnosis and progression phenotypes
No full textBackground: the Alzheimer's Disease COMposite Score (ADCOMS) is more sensitive in clinical trials than conventional measures when assessing pre-dementia. This study compares ADCOMS trajectories using clustered progression characteristics to better understand different patterns of decline.Methods: post-baseline ADCOMS values were analyzed for sensitivity using mean-to-standard deviation ratio (MSDR), partitioned by baseline diagnosis, comparing with the original scales upon which ADCOMS is based. Because baseline diagnosis was not a particularly reliable predictor of progression, individuals were also grouped into similar ADCOMS progression trajectories using clustering methods and the MSDR compared for each progression group.Results: ADCOMS demonstrated increased sensitivity for clinically important progression groups. ADCOMS did not show statistically significant sensitivity or clinical relevance for the less-severe baseline diagnoses and marginal progression groups.Conclusions: this analysis complements and extends previous work validating the sensitivity of ADCOMS. The large data set permitted evaluation-in a novel approach-by the clustered progression group.</p
Occipital lobe and posterior cingulate perfusion in prediction of dementia with Lewy body pathology in a clinical sample
No full textObjective: The aim of this study was to investigate the diagnostic value of occipital lobe and posterior cingulate perfusion in predicting dopamine transporter imaging outcome using a quantitative measure of analysis. Patients and methods: In total, 99 patients with cognitive complaints who had undergone both technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) and 123Iioflupane (123I-FP-CIT also called DaTSCAN) imaging in a dementia diagnostic center were analyzed. Measures of perfusion were calculated from HMPAO SPECT images for the medial and lateral occipital lobe, the posterior cingulate cortex, precuneus and cuneus regions of interest using statistical parametric mapping 8. DaTSCAN images were quantified and specific binding ratios were calculated independent from HMPAO SPECT results. Statistical parametric mapping and tests of associations between perfusion and 123I-FP-CIT imaging were completed. Results: Regions of interest on HMPAO yielded poor predictive values when used independently to predict 123I-FP-CIT status; however, the combination of normal posterior cingulate perfusion with medial and lateral occipital hypoperfusion was associated significantly with 123I-FP-CIT status, χ2 (1, N= 99)=9.72, P = 0.002. This combination also yielded a high positive likelihood ratio and specificity (11.1, 98%). Sensitivity was, however, low (22%). No significant perfusion differences were found when abnormal and normal 123I-FP-CIT groups were compared directly using voxel-based morphometry (P<0.05, family wise error). Conclusion: The combination of medial and lateral occipital hypoperfusion with preserved posterior cingulate gyrus perfusion is highly specific for individuals with a positive 123I-FP-CIT scan in a clinical sample where diagnostic doubt exists. This regional combination, however, lacks sensitivity; therefore, absence of the sign cannot be used to rule out dementia with Lewy bodies. A positive finding provides strong evidence to rule in dementia with Lewy bodies.</p
Increase in Matrix Metaloproteinase‐10 is associated with tau, neurodegeneration and reduced brain perfusion in the right temporal lobe
No full textBackground: blood brain barrier dysfunction amplifies neuroinflammation, which may drive Alzheimer’s Dementia (AD) pathology. Regional cerebral blood flow (RCBF), measured by HMPAO SPECT, is an established biomarker for AD diagnosis. Matrix Metalloproteinase-10 (MMP-10), an enzyme involved in blood brain barrier function through regulating the breakdown of extracellular matrix, was recently proposed as a biomarker of progression to AD. In this study, we examine the relationship between RCBF and levels of MMP-10 in the cerebrospinal fluid (CSF).Materials and methods: datasets of 91 participants from a heterogenous clinical cohort, investigated for dementia due to cognitive complaints were analysed. CSF levels of MMP-10 were measured using the OLINK proximity extension array platform. HMPAO SPECT scans were analysed using Statistical Parametric Mapping (SPM). A univariate linear regression model was used in SPM to quantify the impact of MMP-10 changes on brain perfusion.Results: SPM results showed that higher levels of MMP-10 in CSF are associated with significant reduction in RCBF (family-wise error corrected pConclusion: increased levels of MMP-10 in CSF have been associated with blood brain barrier vulnerability and faster cognitive decline in AD. Here we identified a right sided neuroimaging signature in RCBF with increasing levels MMP-10. This may indicate that by the time of symptoms onset the right side is the fastest progressing as it is catching up with the left side. Right sided changes have been previously associated with delusions, disinhibition and irritability in AD and linked with increased carer burden. The significant reduction in RCBF of the right temporal lobe identified in our study, further reinforces a role for MMP-10 as a marker of progression to AD
CSF markers of inflammation help identify tau pathology but not amyloid in a heterogenous clinical population
No full textBackground: neuroinflammation and activation of the immune system is an integral part of Alzheimer’s Dementia (AD) pathology. Inflammatory mediators exacerbate the production of amyloid-β, the propagation of tau pathology and neuronal loss. This study evaluates whether CSF markers of inflammation can help evaluate changes in amyloid and tau pathology in a heterogenous clinical population.Methods: CSF samples from 105 patients referred to the Wessex Neurology Clinic due to cognitive complaints were analysed. Measurements of AD biomarkers were used to classify the samples based on previously published thresholds (Ab4256pg/ml for a Tau positive test and Total Tau>355pg/ml for a test positive for neurodegeneration). Based on these biomarker results, the likelihood of AD was evaluated using the Paris Lille Montpellier (PLM) scale. 102 markers of inflammation were measured on CSF using the Mesoscale and OLINK platforms. Receiver Operator Characteristic (ROC) curves were used to evaluate if inflammation markers can accurately identify patients with amyloid and tau pathology.Results: 56 patients were amyloid positive, 43 were tau positive and 44 were positive for neurodegeneration. 52 different inflammation markers were detected in over 90% of samples. From these, 26 markers correlate significantly with pTau and Total Tau measurements, while no markers correlate with Ab42 measurements. Adenosine Deaminase (ADA), an enzyme of purine metabolism and marker of cellular immunity, most strongly correlates with pTau and Total Tau (Spearman’s Rho 0.62 and 0.60 respectively, p56pg/ml) with an Area Under the Curve (AUC) of 0.76 and Neurodegeneration positive patients (Total Tau>355pg/ml) with an AUC of 0.82.Conclusion: in this clinical patient cohort, inflammation levels increase with tau pathology but do not change with amyloid. ADA, a marker of cellular immunity, provides a sensitive and specific marker of Tau and Neurodegeneration in AD. Further work is required to assess the prognostic capabilities of ADA in larger patient cohorts and when used in conjunction with established AD biomarkers
Biomarkers of Inflammation Increase with Tau and Neurodegeneration but not with Amyloid-β in a Heterogenous Clinical Cohort
No full textBACKGROUND: Neuroinflammation is an integral part of Alzheimer’s disease (AD) pathology. Inflammatory mediators can exacerbate the production of amyloid-β (Aβ), the propagation of tau pathology and neuronal loss. OBJECTIVE: To evaluate the relationship between inflammation markers and established markers of AD in a mixed memory clinic cohort. METHODS: 105 cerebrospinal fluid (CSF) samples from a clinical cohort under investigation for cognitive complaints were analyzed. Levels of Aβ(42), total tau, and phosphorylated tau were measured as part of the clinical pathway. Analysis of inflammation markers in CSF samples was performed using multiplex immune assays. Participants were grouped according to their Aβ, tau, and neurodegeneration status and the Paris-Lille-Montpellier (PLM) scale was used to assess the likelihood of AD. RESULTS: From 102 inflammatory markers analyzed, 19 and 23 markers were significantly associated with CSF total tau and phosphorylated tau levels respectively (p < 0.001), while none were associated with Aβ(42). The CSF concentrations of 4 inflammation markers were markedly elevated with increasing PLM class indicating increased likelihood of AD (p < 0.001). Adenosine deaminase, an enzyme involved in sleep homeostasis, was the single best predictor of high likelihood of AD (AUROC 0.788). Functional pathway analysis demonstrated a widespread role for inflammation in neurodegeneration, with certain pathways explaining over 30% of the variability in tau values. CONCLUSION: CSF inflammation markers increase significantly with tau and neurodegeneration, but not with Aβ in this mixed memory clinic cohort. Thus, such markers could become useful for the clinical diagnosis of neurodegenerative disorders alongside the established Aβ and tau measures
Imaging care requirements: use of functional neuroimaging to predict dementia caregiver burden
No full textBackground: dementia caregivers frequently report high stress, with increased burden associated with worse outcomes for both patients and caregivers. Although many studies relate clinical phenotypes to burden, the relationship between imaging pathology and burden, irrespective of diagnosis, is unknown. This study investigated the relationship between caregiver burden and patient regional cerebral blood flow in dementia.Methods: seventy-seven patients with cognitive impairment undergoing brain perfusion single-photon emission computed tomography imaging in normal clinical care and their caregivers were recruited. Caregiver burden was ranked from “little” to “severe” using the Zarit Burden Interview and perfusion values extracted from the patient images for predefined regions of interest. The associations between burden score and regional function on imaging were tested.Results: Burden score was significantly higher for caregivers of patients with abnormal perfusion compared to those with normal perfusion in the left and right frontal, right parietal, and right temporal lobes. No difference in burden was found in the left parietal or temporal groups. Correlations showed that a higher caregiver burden was associated with lower patient perfusion scores in the same regions.Conclusion: caregiver burden is strongly related to the extent of frontal or right-predominant parietal or temporal lobe dysfunction. Regional abnormality on perfusion imaging can be used to facilitate identification of individuals who are likely to create a high burden on caregivers.</p
Perfusion imaging and inflammation biomarkers provide complementary information in Alzheimer’s disease
No full textBackground: single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis.Objective: in this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer’s disease (AD).Methods: we analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD.Results: regional perfusion reduction in the precuneus and medial temporal regions predicted Aβ42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85.Conclusions: study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
