Review and Meta-Analysis of Biomarkers and Diagnostic Imaging in Alzheimer's Disease

Abstract

Mild Alzheimer's disease (AD) is often difficult to differentiate from mild cognitive impairment (MCI) or non-AD dementias. A multitude of diagnostic biomarkers and advanced imaging strategies have been developed to aid in the diagnosis and management of AD. We sought to review and analyze the published evidence on key test characteristics of major diagnostic strategies to formulate best estimates of sensitivity (SN) and specificity (SP). A systematic review was undertaken to locate and abstract all studies of biomarkers or diagnostic imaging for AD published in English from January 1990 to March 2010 that provided estimates of SN and SP. Meta-analysis was performed using a bivariate mixed-effects binary regression model. We calculated -SN, SP, and area under the receiver operating curves (AUROC), with confidence and prediction contours. Of 1,840 unique studies identified, 119 presented primary data sufficient for analysis. SN and SP were calculated against non-demented controls, non-AD dementias with and without MCI, if available. Compared to non-demented controls, FDG-PET demonstrated the highest AUROC (0.96), with 90% SN (95%CI 84% to 94%), and 89% SP (95% CI 81% to 94%). FDG-PET also was most accurate in discriminating AD from demented controls (including MCI) with AUROC 0.91, and 92% SN (95%CI 84% to 96%) and 78% SP (95% CI 69% to 85%). For discrimination of AD from non-AD dementias (excluding MCI), CSF Ptau, and SPECT produced identical AUROC (0.86). Diagnostic strategies for AD show wide variation in test characteristics and some show promise for use in clinical practice.

18F-FDG PET Improves Diagnosis in Patients with Focal-Onset Dementias

“…That same year, Silverman et al also published a compelling individual case presentation (27) demonstrating the important benefit obtained with PET metabolic imaging, as shown by its ability to detect AD in a patient who had been given multiple prior incorrect diagnoses of other neuropsychiatric disorders over the course of several years. During the past decade, many studies and literature reviews (28)(29)(30)(31) have demonstrated both the utility and the validity of PET metabolic imaging for evaluating dementia and related neurodegenerative disorders.…”

P1–178: CSF biomarker variability in the Alzheimer's Association quality control program

“…This result is encouraging for the development of validated universal biomarker cutoffs. Also, we would like to emphasize that our results should not delay the implementation of CSF biomarkers for evaluation of patients with AD symptoms in clinical practice at individual centers, because the clinical value of these biomarkers has been established in multiple, independent studies [25]. Rather, the variability stresses (i) the need for all laboratories to strive for longitudinal stability and to use validated internal cutoff levels, and (ii) the need for vendors to deliver more robust assays.…”

Nuclear Medicine Applications in Movement Disorders

“…LCD ile AH'nın ayırıcı tanısında beyin FDG PET görüntüleme bulgularından yararlanılabilir (56,59,60,61,62). LCD'da AH'nda gözlenen temporoparietal hipometabolizmaya ek olarak oksipital de hipometabolizma bulgusu olması (56,59,62) ve posterior singulat korteks metabolizmasının kuneus ile prekuneus metabolizmasına göre daha çok korunmuş olmasından kaynaklanan "singulat adası bulgusu" LCD'nin AH'sinden ayırt edilmesini sağlayan özelliklerdir (62).…”