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1.
Steffen Wolfsgruber Michael Wagner Klaus Schmidtke Lutz Fr?lich Alexander Kurz Stefanie Schulz Harald Hampel Isabella Heuser Oliver Peters Friedel M. Reischies Holger Jahn Christian Luckhaus Michael Hüll Hermann-Josef Gertz Johannes Schr?der Johannes Pantel Otto Rienhoff Eckart Rüther Fritz Henn Jens Wiltfang Wolfgang Maier Johannes Kornhuber Frank Jessen 《PloS one》2014,9(7)
Background
Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).Methods
We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.Results
Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.Conclusions
Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI. 相似文献2.
Ilaria Cova Francesca Clerici Annalia Rossi Valentina Cucumo Roberta Ghiretti Laura Maggiore Simone Pomati Daniela Galimberti Elio Scarpini Claudio Mariani Barbara Caracciolo 《PloS one》2016,11(3)
Background
Weight loss is common in people with Alzheimer’s disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown.Aims
To assess weight loss as a predictor of dementia and AD in MCI.Methods
One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight.Results
Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5–6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4–8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD.Conclusions
Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment. 相似文献3.
Sei J. Lee Christine S. Ritchie Kristine Yaffe Irena Stijacic Cenzer Deborah E. Barnes 《PloS one》2014,9(12)
Background
Mild cognitive impairment is often a precursor to dementia due to Alzheimer''s disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.Objective
To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.Design and Participants
382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer''s Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.Main Predictors Measures
Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.Main Outcome Measure
Progression to probable Alzheimer''s disease.Key Results
Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer''s disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell''s c-statistic was 0.71(95% CI: 0.68–0.75). Fourteen percent of subjects with low risk scores (0–2 points, n = 124) converted to probable Alzheimer''s disease over 3 years, compared to 51% of those with moderate risk scores (3–8 points, n = 223) and 91% of those with high risk scores (9–16 points, n = 35).Conclusions
An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer''s disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression. 相似文献4.
《PloS one》2015,10(11)
Background
Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI).Methods
Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment.Results
The published range of MCI prevalence estimates was 5.0%–36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%–10.8%); Clinical Dementia Rating of 0.5 (1.8%–14.9%); Mini-Mental State Examination score of 24–27 (2.1%–20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01).Conclusion
Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally. 相似文献5.
Malgorzata Gorska-Ciebiada Malgorzata Saryusz-Wolska Anna Borkowska Maciej Ciebiada Jerzy Loba 《PloS one》2015,10(3)
Objective
The aim of the study was to determine the serum levels of CRP, IL-6 and TNF-α in elderly diabetic patients with depressive syndrome alone or with coexisting mild cognitive impairment (MCI).Methods
276 diabetics elders were screened for depressive symptoms (using Geriatric Depression Scale: GDS-30) and MCI (using the Montreal Cognitive Assessment: MoCA score). Data of HbA1c, blood lipids and inflammatory markers levels were collected.Results
In all groups of patients levels of CRP, IL-6 and TNF-α were significantly higher as compared to controls. The highest level of inflammatory markers was detected in group with depressive mood and coexisting MCI, however IL-6 level didn’t significantly differ as compared to MCI group. We founded correlations between all inflammatory markers in group of patients with depressive mood and in group of subjects with depressive symptoms and coexisting MCI. GDS-30 score was correlated with levels of inflammatory markers in group with depressive mood, and with levels of CRP and TNF-α in group with depressive mood and coexisting MCI. In the group with depressive mood and coexisting MCI we founded that MoCA score was negatively correlated with CRP and TNF-α levels; and HbA1c level was positively correlated with all inflammatory markers. The univariate logistic regression models revealed that variables which increased the likelihood of having been diagnosed with MCI in depressed patients were: higher levels of HbA1c, CRP, IL-6 and TNF-α, previous CVD or stroke, increased number of co-morbidities and microvascular complications, older age, less years of formal education. The multivariable model showed that previous CVD, higher HbA1c and IL-6 levels are significant factors.Conclusions
We demonstrated that the presence of depressive syndrome is associated with higher levels of inflammatory markers in elderly patients with diabetes. The presence of MCI in these depressed subjects has additive effect on levels of inflammatory mediators. 相似文献6.
Simona Littnerova Petr Kala Jiri Jarkovsky Lenka Kubkova Krystyna Prymusova Petr Kubena Martin Tesak Ondrej Toman Martin Poloczek Jindrich Spinar Ladislav Dusek Jiri Parenica 《PloS one》2015,10(4)
Aim
To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients.Methods and Results
A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores—the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE—showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73–0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80–0.83).Conclusions
All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model. 相似文献7.
Sang Joon Son Kang Soo Lee Ji Hyung Chung Ki Jung Chang Hyun Woong Roh Soo Hyun Kim Taewon Jin Joung Hwan Back Hyun Jung Kim Yunhwan Lee Seong Hye Choi Jai Sung Noh Ki Young Lim Young Ki Chung Chang Hyung Hong Byoung Hoon Oh 《PloS one》2015,10(3)
Background and Aims
Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline.Methods
Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed.Results
After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001).Conclusions
These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly. 相似文献8.
Sebastian Heinzel Florian G. Metzger Ann-Christine Ehlis Robert Korell Ahmed Alboji Florian B. Haeussinger Isabel Wurster Kathrin Brockmann Ulrike Suenkel Gerhard W. Eschweiler Walter Maetzler Daniela Berg Andreas J. Fallgatter 《PloS one》2015,10(9)
Background
Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer''s disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands.Methods
Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated.Results
Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics.Conclusion
Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia. 相似文献9.
Background/Aims
To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer''s Disease Neuroimaging Initiative (ADNI).Methods
Sample statistics were computed from ADNI cohorts with no cognitive diagnosis, a diagnosis of mild cognitive impairment (MCI), and a diagnosis of possible or probable Alzheimer''s disease (AD). Nine different definitions of IIV were computed for each sample, and standardized effect sizes (Cohen''s d) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately (‘within test’ IIV) and the two tests together (‘across test’ IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer''s Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician''s Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals.Results
ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary.Conclusion
IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance. 相似文献10.
Desikan RS Sabuncu MR Schmansky NJ Reuter M Cabral HJ Hess CP Weiner MW Biffi A Anderson CD Rosand J Salat DH Kemper TL Dale AM Sperling RA Fischl B;Alzheimer's Disease Neuroimaging Initiative 《PloS one》2010,5(9):e12853
Background
Alzheimer''s disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown.Methodology/Principal Findings
In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) Aß levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer''s pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (n = 724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals.Conclusions/Significance
Cortical Aβ and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer''s pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia. 相似文献11.
Jung-Lung Hsu Wei-Ju Lee Yi-Chu Liao Jiing-Feng Lirng Shuu-Jiun Wang Jong-Ling Fuh 《PloS one》2015,10(9)
Background
Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was correlated with cognitive and non-cognitive symptoms in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients are unclear.Methods
Patients with probable AD and MCI from a medical center outpatient clinic received attention, memory, language, executive function evaluation and Mini-Mental Status Examination (MMSE). The severity of dementia was rated by the Clinical Dementia Rating (CDR) Sum of Box (CDR-SB). The neuropsychiatric inventory (NPI) subscale of agitation/aggression and mood symptoms was also applied. Magnetic resonance imaging (MRI) was scored visually for the MTA, PA and white matter hyperintensity (WMH) scores.Results
We recruited 129 AD and 31 MCI (mean age 78.8 years, 48% female) patients. MMSE scores, memory, language and executive function were all significantly decreased in individuals with AD than those with MCI (p < 0.01). MTA and PA scores reflected significant atrophy in AD compared to MCI; however, the WMH scores did not differ. The MTA scores were significantly correlated with the frontal, parieto-occipital and global WMH scores (p < 0.01) while the PA scores showed a correlation with the parieto-occipital and temporal WMH scores (p < 0.01). After adjusting for age, education, APOE4 gene and diagnostic group covariates, the MTA scores showed a significant association with MMSE and CDR-SB, while the right side PA scores were significantly associated with NPI-agitation/aggression subscales (p < 0.01).Conclusion
Regional atrophy is related to different symptoms in patients with AD or MCI. PA score is useful as a complementary measure for non-cognitive symptom. 相似文献12.
13.
Jianfeng Luo Bei Wu Qianhua Zhao Qihao Guo Haijiao Meng Lirong Yu Li Zheng Zhen Hong Ding Ding 《PloS one》2015,10(3)
Background
Oral health has been found to be associated with cognitive function in basic research and epidemiology studies. Most of these studies had no comprehensive clinical diagnosis on cognitive function. This study firstly reported the association between tooth loss and cognitive function among Chinese older population.Methods
The study included 3,063 community dwelling older adults aged 60 or above from the Shanghai Aging Study. Number of teeth missing was obtained from self-reporting questionnaire and confirmed by trained interviewers. Participants were diagnosed as “dementia”, “mild cognitive impairment (MCI)”, or “cognitive normal” by neurologists using DSM-IV and Petersen criteria. Multivariate logistic regression model was applied to examine the association between number of teeth missing and cognitive function.Results
The study participants had an average of 10.2 teeth lost. Individuals with dementia lost 18.7 teeth on average, much higher than those with MCI (11.8) and cognitive normal (9.3) (p<0.001). After adjusted for sex, age, education year, living alone, body mass index, cigarette smoking, alcohol drinking, anxiety, depression, heart disease, hypertension, diabetes, and APOE-ε4, tooth loss of >16 were significantly associated with dementia with an OR of 1.56 (95%CI 1.12-2.18).Conclusion
Having over 16 missing teeth was associated with severe cognitive impairment among Chinese older adults. Poor oral health might be considered as a related factor of neurodegenerative symptom among older Chinese population. 相似文献14.
Objectives
A phase of mild cognitive impairment (MCI) precedes most forms of neurodegenerative dementia. Many definitions of MCI recommend the use of test norms to diagnose cognitive impairment. It is, however, unclear whether the use of norms actually improves the detection of individuals at risk of dementia. Therefore, the effects of age- and education-norms on the validity of test scores in predicting progression to dementia were investigated.Methods
Baseline cognitive test scores (Syndrome Short Test) of dementia-free participants aged ≥65 were used to predict progression to dementia within three years. Participants were comprehensively examined one, two, and three years after baseline. Test scores were calculated with correction for (1) age and education, (2) education only, (3) age only and (4) without correction. Predictive validity was estimated with Cox proportional hazard regressions. Areas under the curve (AUCs) were calculated for the one-, two-, and three-year intervals.Results
82 (15.3%) of initially 537 participants, developed dementia. Model coefficients, hazard ratios, and AUCs of all scores were significant (p<0.001). Predictive validity was the lowest with age-corrected scores (−2 log likelihood = 840.90, model fit χ2 (1) = 144.27, HR = 1.33, AUCs between 0.73 and 0.87) and the highest with education-corrected scores (−2 log likelihood = 815.80, model fit χ2 (1) = 171.16, HR = 1.34, AUCs between 0.85 and 0.88).Conclusion
The predictive validity of test scores is markedly reduced by age-correction. Therefore, definitions of MCI should not recommend the use of age-norms in order to improve the detection of individuals at risk of dementia. 相似文献15.
Niskanen E Könönen M Määttä S Hallikainen M Kivipelto M Casarotto S Massimini M Vanninen R Mervaala E Karhu J Soininen H 《PloS one》2011,6(10):e26113
Background:
Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.Methodology and Principal Findings:
To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer''s disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.Conclusions:
In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD. 相似文献16.
Katherine A. Gifford Dandan Liu Timothy J. Hohman Meng Xu Xue Han Raymond R. Romano III Laura R. Fritzsche Ty Abel Angela L. Jefferson 《PloS one》2015,10(11)
Background
This study examines whether different sources of cognitive complaint (i.e., self and informant) predict Alzheimer’s disease (AD) neuropathology in elders with mild cognitive impairment (MCI).Methods
Data were drawn from the National Alzheimer’s Coordinating Center Uniform and Neuropathology Datasets (observational studies) for participants with a clinical diagnosis of MCI and postmortem examination (n = 1843, 74±8 years, 52% female). Cognitive complaint (0.9±0.5 years prior to autopsy) was classified into four mutually exclusive groups: no complaint, self-only, informant-only, or mutual (both self and informant) complaint. Postmortem neuropathological outcomes included amyloid plaques and neurofibrillary tangles. Proportional odds regression related complaint to neuropathology, adjusting for age, sex, race, education, depressed mood, cognition, APOE4 status, and last clinical visit to death interval.Results
Mutual complaint related to increased likelihood of meeting NIA/Reagan Institute (OR = 6.58, p = 0.004) and Consortium to Establish a Registry for Alzheimer’s Disease criteria (OR = 5.82, p = 0.03), and increased neurofibrillary tangles (OR = 3.70, p = 0.03), neuritic plaques (OR = 3.52, p = 0.03), and diffuse plaques (OR = 4.35, p = 0.02). Informant-only and self-only complaint was not associated with any neuropathological outcome (all p-values>0.12).Conclusions
In MCI, mutual cognitive complaint relates to AD pathology whereas self-only or informant-only complaint shows no relation to pathology. Findings support cognitive complaint as a marker of unhealthy brain aging and highlight the importance of obtaining informant corroboration to increase confidence of underlying pathological processes. 相似文献17.
Background
Used as contrast agents for brain magnetic resonance imaging (MRI), markers for beta-amyloid deposits might allow early diagnosis of Alzheimer''s disease (AD). We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore), should it become clinically available.Methodology/Principal Findings
We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI). In alternative “screen and treat” scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population). We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses.The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the “screen and treat” analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%.Conclusions/Significance
It is thought that anti-beta-amyloid compounds might halt the development of dementia in early stage patients. This study suggests that, even should such treatments become available, systematically screening the over-60 population for AD would only become cost-effective with highly specific tests able to diagnose early stages of the disease. However, offering a new diagnostic test based on beta-amyloid markers to elderly patients with MCI might prove cost-effective. 相似文献18.
Emily N. Manning Josephine Barnes David M. Cash Jonathan W. Bartlett Kelvin K. Leung Sebastien Ourselin Nick C. Fox for the Alzheimer's Disease NeuroImaging Initiative 《PloS one》2014,9(5)
Objectives
To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer''s disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates.Methods
MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into “progressors” (MCI-P) if diagnosed with AD within 36 months or “stable” (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.Results
Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.Conclusions
These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD. 相似文献19.
Dillys van Vliet Ariel Alonso Ger Rijkers Jan Heynens Philippe Rosias Jean Muris Quirijn J?bsis Edward Dompeling 《PloS one》2015,10(3)
Background
In asthma management guidelines the primary goal of treatment is asthma control. To date, asthma control, guided by symptoms and lung function, is not optimal in many children and adults. Direct monitoring of airway inflammation in exhaled breath may improve asthma control and reduce the number of exacerbations.Aim
1) To study the use of fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC), in the prediction of asthma exacerbations in a pediatric population. 2) To study the predictive power of these exhaled inflammatory markers combined with clinical parameters.Methods
96 asthmatic children were included in this one-year prospective observational study, with clinical visits every 2 months. Between visits, daily symptom scores and lung function were recorded using a home monitor. During clinical visits, asthma control and FeNO were assessed. Furthermore, lung function measurements were performed and EBC was collected. Statistical analysis was performed using a test dataset and validation dataset for 1) conditionally specified models, receiver operating characteristic-curves (ROC-curves); 2) k-nearest neighbors algorithm.Results
Three conditionally specified predictive models were constructed. Model 1 included inflammatory markers in EBC alone, model 2 included FeNO plus clinical characteristics and the ACQ score, and model 3 included all the predictors used in model 1 and 2. The area under the ROC-curves was estimated as 47%, 54% and 59% for models 1, 2 and 3 respectively. The k-nearest neighbors predictive algorithm, using the information of all the variables in model 3, produced correct predictions for 52% of the exacerbations in the validation dataset.Conclusion
The predictive power of FeNO and inflammatory markers in EBC for prediction of an asthma exacerbation was low, even when combined with clinical characteristics and symptoms. Qualitative improvement of the chemical analysis of EBC may lead to a better non-invasive prediction of asthma exacerbations. 相似文献20.
Kakimoto A Kamekawa Y Ito S Yoshikawa E Okada H Nishizawa S Minoshima S Ouchi Y 《PloS one》2011,6(9):e25033