Differential Diagnosis Of Alzheimer's Disease Research Articles

Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD.

The identification of reliable diagnostic tools for the differential diagnosis between sporadic Creutzfeldt-Jakob Disease (sCJD) and Alzheimer's disease (AD) remains impeded by the existing clinical, neuropathological and molecular overlap between both diseases. The development of new tools for the quantitative measurement of biomarkers is gaining experimental momentum due to recent advances in high-throughput screening analysis and with the optimization of assays for their quantification in biological fluids, including cerebrospinal fluid (CSF). Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve clinical quality performance in a variety of sample types due to its high sensitivity and dynamic range. Here, we quantified the CSF levels of Tau-protein, β-amyloid 1-42 (Aβ42) and α-synuclein, as important biomarkers in CSF used in the differential diagnosis of neurodegenerative disorders in 12 AD, 12 sCJD and 12 control cases by singleplex ECL-based technology. Its performance has been compared to classical enzyme-linked immunosorbent assays (ELISA) to confront their clinical accuracy. ECL-based technology validates previous data obtained with ELISA and presents a higher performance in the discrimination of three analysed groups as determined by increased area under the curve (AUC) values for the three biomarkers. Importantly, α-synuclein levels detected by ECL allow an excellent discrimination between sCJD cases and AD and control cases, unveiling a new clinical approach for the differential diagnosis of sCJD.

PET-imaging of Cerebral Glucose Metabolism and of Cerebral Beta-amyloid-deposition and Its Value for the Understanding, Early Detection and Differential Diagnosis of Alzheimer's Disease

Alzheimer’s disease is now seen as a process that starts decades before cognitive impairment occurs and becomes severe enough to cause dementia. It has been acknowledged, that biomarkers of this process (e.g.: CSF, structural MRI,FDG-PET (positron emission tomography), Amyloid-PET) increase diagnostic certainty and facilitate early diagnosis under the ultimate goal of early intervention. This presentation will focus on PET-imaging of cerebral glucose metabolism by18-[F]-FDG-PET and cerebral beta-amyloid-deposition by the amyloid-binding PET Tracers (11-[C]-PiB, 18-[F]-Florbetapir, 18-[F]-Flutemetamol) and its value for the understanding, early detection and differential diagnosis of Alzheimer’sdisease. It will highlight clinical situations in which these diagnostics are considered useful and potential caveats. Finally it will provide a perspective how dementia diagnostics may evolve to in vivo assessment of pathology that predicts clinical phenotype and ideally therapeutic intervention.

Smell identification function and Alzheimer's disease: a selective review.

To provide an update of the recent studies on the olfactory function in Alzheimer's disease, with a focus on the olfactory identification function. The studies reviewed here confirm previous reports on the poor olfactory function in Alzheimer's disease compared to health normal controls and also as a marker for conversion from mild cognitive impairment to Alzheimer's disease. Olfactory identification function has been associated with severity of illness, non-cognitive neuropsychiatric symptoms, and structural and functional MRI measures. There is a possible interaction of apolipoprotein E genotype with olfactory performance in Alzheimer's disease patients and those at risk for Alzheimer's disease. Usefulness of smell identification function in differentiating Alzheimer's disease patients from other types of dementia needs to be established. The need for simple, inexpensive and non-invasive procedures for aiding in the diagnosis and understanding of Alzheimer's disease has led to theories and procedures examining the role of olfactory functions in Alzheimer's disease. Although there is increasing evidence for olfactory dysfunction in general and impaired odour identification in particular in Alzheimer's disease, additional larger and methodologically sound research is needed for testing its clinical utility in day-to-day clinical practice for early, accurate and differential diagnosis of Alzheimer's disease.

Cerebrospinal fluid β-amyloid1-42 levels in the differential diagnosis of Alzheimer's disease--systematic review and meta-analysis.

ObjectivesThe purpose of this study was to carry out systematic review of the literature and meta-analysis to evaluate the diagnostic utility of cerebrospinal fluid (CSF) levels of the 42 amino acid form of amyloid-beta (Aβ1–42) as a biomarker for differentiating Alzheimer’s disease (AD) from non-AD dementia.Methods Design. Systematic literature review was used to evaluate the effectiveness of the Aβ for the diagnosis of AD. The Scottish Intercollegiate Guidelines Network (SIGN) tool was used to evaluate independently the quality of the studies. Data sources. The literature review covered from January 1, 2004, to October 22, 2013, and searched eight domestic databases including Korea Med and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library. Data Extraction and Synthesis. Primary criteria for inclusion were valid studies on (i) patients with mild cognitive impairment with confirmed or suspected AD and non-AD dementia, and (ii) assessment of Aβ1–42 levels using appropriate comparative tests.ResultsA total of 17 diagnostic evaluation studies were identified in which levels of CSF Aβ1–42 were assessed. Meta-analysis was performed on 11 robust studies that compared confirmed AD (n = 2211) with healthy individuals (n = 1030), 10 studies that compared AD with non-AD dementias (n = 627), and 5 studies that compared amnestic mild cognitive impairment (n = 1133) with non-amnestic type subjects (n = 1276). Overall, the CSF Aβ1–42 levels were reduced in AD compared to controls or non-AD dementia. The effectiveness of test was evaluated for diagnostic accuracy (pooled sensitivity, 0.80 (95% CI 0.78–0.82); pooled specificity, 0.76 (95% CI 0.74–0.78).ConclusionsReduced CSF Aβ1–42 levels are of potential utility in the differential diagnosis of AD versus non-AD dementias and controls. Diagnostic accuracy was high in AD versus healthy controls. However, differential diagnosis for MCI or non-AD might be evaluated by other biomarkers.

Diagnóstico diferencial etiopatogénico de las demencias: enfermedad de Alzheimer

Various complementary tests are employed in the differential diagnosis of Alzheimer's disease, and they can be grouped into several levels according to their accessibility, objectives and complexity. Level I (basic studies) includes tests that should be routinely requested. Level II tests (complementary studies) are those employed in cases of cognitive impairment with atypical presentation. Level III tests (specific studies) are those that should be used to confirm a specific clinical suspicion. Level IV tests (clinical research studies) are those reserved for research or highly specialized centers.

MOCA SUBSCORES TO DIAGNOSE DEMENTIA SUBTYPES: INITIAL STUDY

ObjectiveTo report derivation of subscores from the Montreal Cognitive Assessment (MoCA) analogous to those derived from MMSE (MoCA Ala score) and Addenbrooke's Cognitive Examination (MoCA VLOM ratio) and examine their...

The Role of Neurosonology in the Diagnosis of Vascular Dementia

Although transcranial sonography is not yet an established diagnostic modality for dementia screening or differential diagnosis of Alzheimer's disease (AD) from vascular dementia (VaD), intracranial hemodynamic assessment may provide crucial information about the association between cognitive deterioration and vascular risk factors. We conducted a systematic narrative review of available literature through MEDLINE and EMBASE search to identify all available data about the evaluation of VaD patients with transcranial Doppler, and to discuss further the vascular disorders of the cerebral circulation in patients with vascular cognitive impairment. According to the available literature data to date, VaD patients were found to have lower mean flow velocity values in four studies (indicating cerebral hypoperfusion), higher pulsatility indices in three studies (indicating increased downstream vascular resistance), and more severe impairment of cerebrovascular reactivity in five studies (indicating exhausted vasodilatory reserve) compared to AD patients and controls. Microembolic signals were also found to be significantly more common in patients with VaD or AD compared to their age- and gender-matched controls, suggesting that asymptomatic microembolism, apart for being only marker of VaD, could presumably be involved in the genesis of dementia, and in the overlap between VaD and AD. Further studies with larger and carefully selected groups are required to eliminate potential confounders and to set specific cut-off values for the aforementioned hemodynamic parameters in demented patients and dementia subtypes.

Raman spectroscopy detection of platelet for Alzheimer’s disease with predictive probabilities

Alzheimer’s disease (AD) is a common form of dementia. Early and differential diagnosis of AD has always been an arduous task for the medical expert due to the unapparent early symptoms and the currently imperfect imaging examination methods. Therefore, obtaining reliable markers with clinical diagnostic value in easily assembled samples is worthy and significant. Our previous work with laser Raman spectroscopy (LRS), in which we detected platelet samples of different ages of AD transgenic mice and non-transgenic controls, showed great effect in the diagnosis of AD. In addition, a multilayer perception network (MLP) classification method was adopted to discriminate the spectral data. However, there were disturbances, which were induced by noise from the machines and so on, in the data set; thus the MLP method had to be trained with large-scale data. In this paper, we aim to re-establish the classification models of early and advanced AD and the control group with fewer features, and apply some mechanism of noise reduction to improve the accuracy of models. An adaptive classification method based on the Gaussian process (GP) featured, with predictive probabilities, is proposed, which could tell when a data set is related to some kind of disease. Compared with MLP on the same feature set, GP showed much better performance in the experimental results. What is more, since the spectra of platelets are isolated from AD, GP has good expansibility and can be applied in diagnosis of many other similar diseases, such as Parkinson’s disease (PD). Spectral data of 4 month and 12 month AD platelets, as well as control data, were collected. With predictive probabilities, the proposed GP classification method improved the diagnostic sensitivity to nearly 100%. Samples were also collected from PD platelets as classification and comparison to the 12 month AD. The presented approach and our experiments indicate that utilization of GP with predictive probabilities in platelet LRS detection analysis turns out to be more accurate for early and differential diagnosis of AD and has a wide application prospect.

Differential diagnosis of degenerative dementias using basic neuropsychological tests: multivariable logistic regression analysis of 301 patients.

The validity of neuropsychological tests for the differential diagnosis of degenerative dementias may depend on the clinical context. We constructed a series of logistic models taking into account this factor. We retrospectively analyzed the demographic and neuropsychological data of 301 patients with probable Alzheimer's disease (AD), frontotemporal degeneration (FTLD), or dementia with Lewy bodies (DLB). Nine models were constructed taking into account the diagnostic question (eg, AD vs DLB) and subpopulation (incident vs prevalent). The AD versus DLB model for all patients, including memory recovery and phonological fluency, was highly accurate (area under the curve = 0.919, sensitivity = 90%, and specificity = 80%). The results were comparable in incident and prevalent cases. The FTLD versus AD and DLB versus FTLD models were both inaccurate. The models constructed from basic neuropsychological variables allowed an accurate differential diagnosis of AD versus DLB but not of FTLD versus AD or DLB.

Diffusion tensor imaging study of the temporal stem in Alzheimer's disease

Objective To study the changes of fractional anisotropy (FA) value of white matter of brain and temporal stem in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients as well as normal cognitive (NC) aged people with diffusion tensor imaging (DTI), and explore the damage mechanism of temporal stem and its diagnostic value on AD and aMCI. Methods Ten patients with AD, 10 patients with aMCI and 10 NC volunteers as control group were scanned by routine MRI and DTI. FA values were calculated by post-processing software (DTIstudio) in temporal stem (including anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus), and white matter in anterior frontal, temperal, parietal and occipital lobes. The data were analyzed by SPSS 13.0. If bilateral differences of FA values were not statistically significant (P > 0.05), the average values of bilateral FA were selected and compared among 3 groups. If bilateral differences of FA values were statistically significant (P 0.05, for all). 2) There was significant difference of FA values in anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus between AD and aMCI groups (P 0.05, for all). Conclusions The significant difference of FA values in temporal stem among AD, aMCI and NC groups suggests that temporal stem fiber bundles are of great significance in the white matter damage of AD, and DTI is helpful for the differential diagnosis of AD, aMCI and NC. The abnormal changes of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal and parietal lobes are of great diagnostic value in AD. doi: 10.3969/j.issn.1672-6731.2014.03.011

Molecular Imaging of Alzheimer Disease Pathology

Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

A survey of FDG- and amyloid-PET imaging in dementia and GRADE analysis.

PET based tools can improve the early diagnosis of Alzheimer's disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject's scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations.

Efficacy of the Phosphorylated tau 181 in Differential Diagnosis of the Alzheimer's Disease: A Systematic Review and Meta-Analysis

Background: The purpose of this study was to evaluate the value of phosphorylated tau with epitopes threonine 181(p-tau181) in cerebrospinal fluid (CSF) for the differential diagnosis of Alzheimer's disease typed dementia from other type of dementia. Methods: A systematic literature search was performed to identify studies on p-tau181. Two evaluators independently evaluated the quality of the ten studies using the Scottish Intercollegiate Guidelines Network (SIGN) tool. The literature review covered from October 27, 1946 to October 22, 2013, and eight domestic databases including KoreaMed and international data- bases including Ovid-MEDLINE, EMBASE, and Cochrane Library were used. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta- analysis. Outcome measures were Cohen's delta, sensitivity and specificity. Results: Finally, 8 studies (8 diagnostic evaluation studies) were identified to evaluate CSF p-tau181. The effectiveness of this test was evaluated based on diagnostic accuracy. The diagnostic accuracy for identifying AD by ELISA was high which revealed pooled sensitivity as 0.843 (95% CI 0.818-0.867), pooled specificity as 0.799(95% CI 0.768-0.828) and summary receiver operating characteristic area under the curve 0.9082 ± 0.0236. Con- clusions: CSF p-tau181 concentrations in other type of dementia are intermediate between controls and AD patients. Overlap between both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed.

The Diagnostic Value of CSF Amyloid-β<sub>43</sub> in Differentiation of Dementia Syndromes

Amyloid-β (Aβ) is known as the most prominent core protein in Alzheimer's Disease (AD) senile plaques. Although research has focused mainly on Aβ40 and Aβ42 as potential cerebrospinal fluid (CSF) biomarkers, a range of Aβ peptides with variable lengths has been demonstrated in the brains and CSF of AD patients. Recently, it has been found that the Aβ43 peptide may be more abundant than previously assumed, could therefore play an important role in AD pathophysiology, and hence also function as putative biomarker. In this study the value of CSF Aβ43 in AD diagnosis was investigated. Aβ43 levels in CSF were highly correlated with Aβ42 levels. Furthermore, in differentiation of AD from nondemented controls and from patients with Lewy body dementia and frontotemporal dementia, Aβ43 had an equal diagnostic value as Aβ42, both as a single biomarker and in combination with total and phosphorylated tau. In conclusion, quantification of Aβ43 in CSF does not add novel diagnostic information to the differential diagnosis of AD compared to existing biomarkers.

Cerebrospinal fluid τ protein in differential diagnosis of Alzheimer's disease and vascular dementia in Chinese population: a meta-analysis.

To assess whether biomarker τ protein could differentiate between Alzheimer's disease (AD) and vascular dementia (VaD). We conducted a comprehensive search to identify studies on τ protein, patients with AD, and patients with VaD. Cerebrospinal fluid (CSF) τ protein levels were compared to discriminate among patients with AD, healthy controls, and patients with VaD by a meta-analysis. Patients with AD exhibit significantly higher CSF τ protein levels than healthy controls or patients with VaD in the Chinese population. Our findings suggested that CSF τ protein levels were found to be significantly associated with AD in the Chinese population. Measurement of τ protein could help in attenuating the strict distinction between AD and VaD.

The role of ASL-measured cerebral blood flow in the differential diagnosis of Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies

The role of ASL-measured cerebral blood flow in the differential diagnosis of Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies

The role of ASL-measured cerebral blood flow in the differential diagnosis of Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies

The role of ASL-measured cerebral blood flow in the differential diagnosis of Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies

CSF levels of the neuronal injury biomarker visinin‐like protein‐1 in Alzheimer's disease and dementia with Lewy bodies

The overlapping clinical features of Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB) make differentiation difficult in the clinical environment. Evaluating the CSF levels of biomarkers in AD and DLB patients could facilitate clinical diagnosis. CSF Visinin-like protein-1 (VILIP-1), a calcium-mediated neuronal injury biomarker, has been described as a novel biomarker for AD. The aim of this study was to investigate the diagnostic utility of CSF VILIP-1 and VILIP-1/Aβ1-42 ratio to distinguish AD from DLB. Levels of CSF VILIP-1, t-tau, p-tau181P , Aβ1-42 , and α-synuclein were measured in 61 AD patients, 32 DLB patients, and 40 normal controls using commercial ELISA kits. The results showed that the CSF VILIP-1 level had significantly increased in AD patients compared with both normal controls and DLB patients. The CSF VILIP-1 and VILIP-1/Aβ1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. Additionally, CSF VILIP-1 levels were positively correlated with t-tau and p-tau181P within each group and with α-synuclein in the AD and control groups. We conclude that CSF VILIP-1 could be a diagnostic marker for AD, differentiating it from DLB. The analysis of biomarkers, representing different neuropathologies, is an important approach reflecting the heterogeneous features of AD and DLB. Neuronal Ca(2+) -sensor protein VILIP-1 has been implicated in the calcium-mediated neuronal injury and pathological change of AD. The CSF VILIP-1 and VILIP-1/Aβ1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. CSF VILIP-1 is a useful biomarker for AD. Evaluating the CSF levels of VILIP-1 in AD and DLB patients could facilitate clinical diagnosis.

Laser Raman detection of platelets for early and differential diagnosis of Alzheimer’s disease based on an adaptive Gaussian process classification algorithm

Early and differential diagnosis of Alzheimer’s disease (AD) has puzzled many clinicians. In this work, laser Raman spectroscopy (LRS) was developed to diagnose AD from platelet samples from AD transgenic mice and non-transgenic controls of different ages. An adaptive Gaussian process (GP) classification algorithm was used to re-establish the classification models of early AD, advanced AD and the control group with just two features and the capacity for noise reduction. Compared with the previous multilayer perceptron network method, the GP showed much better classification performance with the same feature set. Besides, spectra of platelets isolated from AD and Parkinson’s disease (PD) mice were also discriminated. Spectral data from 4 month AD (n = 39) and 12 month AD (n = 104) platelets, as well as control data (n = 135), were collected. Prospective application of the algorithm to the data set resulted in a sensitivity of 80%, a specificity of about 100% and a Matthews correlation coefficient of 0.81. Samples from PD (n = 120) platelets were also collected for differentiation from 12 month AD. The results suggest that platelet LRS detection analysis with the GP appears to be an easier and more accurate method than current ones for early and differential diagnosis of AD.

Action and noun fluency testing to distinguish between Alzheimer's disease and dementia with Lewy bodies

The objective of the present study was to establish whether performance in an action fluency task is of value in the differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). After collecting normative data on performance in an action fluency task and a conventional animal fluency task in a cohort of French-speaking healthy controls, we assessed AD and DLB patients. Only the action fluency score differed significantly between the two demented groups, with DLB patients performing worse than AD patients. However, a composite action and animal fluency score was found to be more effective for discriminating between these two groups.