Individuals diagnosed as having mild cognitive impairment (MCI) have a high likelihood of progressing to dementia within 3 to 5 years, but not all individuals with MCI progress to dementia. Prognostic uncertainty suggests the need for additional measures to assist the clinician.
To assess the added value of qualitative measures of medial temporal atrophy (MTA) to estimate the relative risk of progressing from MCI to dementia.
A 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study initially designed to evaluate the efficacy of donepezil hydrochloride or vitamin E vs placebo to delay progression of MCI to dementia.
Memory assessment centers.
A total of 190 individuals with MCI.
Ratings of MTA performed using magnetic resonance images obtained at baseline. Log-rank tests and Cox proportional hazards ratios examining the significance of MTA estimates in predicting progression of MCI to dementia.
A mean MTA score greater than 2.0 was associated with a greater than 2-fold increased likelihood of progression to dementia during the observation period (hazards ratio, 2.30; 95% confidence interval, 1.09-4.92; P = .03) after controlling for age, education, sex, and baseline Mini-Mental State Examination score.
Adjusted estimates of MTA were associated with significantly increased risk of developing dementia within 3 years, suggesting that obtaining a magnetic resonance image during the evaluation of MCI may offer additional independent information about the risk of progression to dementia. Given the relatively high prevalence of MCI in the general population, use of this method as part of routine clinical evaluation may help identify individuals who might benefit from increased surveillance and future treatment.
clinicaltrials.gov Identifier: NCT00000173.
"A primary focus of research in AD is identifying which biomarkers are clinically useful for the early diagnosis of AD. Medial temporal lobe (MTL) atrophy as assessed using structural magnetic resonance imaging (MRI) has proven to be an effective clinical aid in the early diagnosis of AD (Visser et al., 2002a), and this method predicts AD in subjects with mild cognitive impairment (MCI) (DeCarli et al., 2007; Rusinek et al., 2004; Schoonenboom Contents lists available at SciVerse ScienceDirect "
[Show abstract][Hide abstract] ABSTRACT: Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n = 156) and the single-center VU medical center (n = 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1-42. MTA-score and lateral ventricle volume correlated with CSF beta-amyloid 1-42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI.
Neurobiology of aging 03/2013; 34(8). DOI:10.1016/j.neurobiolaging.2013.02.002 · 5.01 Impact Factor
"As the aforementioned methods have disadvantages of requiring significant time and complex programs to be applied to actual clinical practices, the clinical application of MTA is limited. However, many previous clinical studies reported that MTA was important for distinguishing early AD patients from normal or patients with mild cognitive impairment. In addition, with respect to the usefulness of visual rating scale, Burton reported that MTA on MRI, which was measured using VRS, had robust discriminatory power for screening and diagnosing AD, Lewy body dementia and vascular cognitive impairment in dementia patients who were pathologically verified and that its sensitivity and specificity were 91% and 94%, respectively. "
[Show abstract][Hide abstract] ABSTRACT: The Korean version of Mini-Mental Status Examination (K-MMSE) and the Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated as quick neuropsychological tests for screening dementia in various clinical settings. Medial temporal atrophy (MTA) is an early pathological characteristic of Alzheimer's disease (AD). We aimed to assess the diagnostic validity of the fusion of the neuropsychological test and visual rating scale (VRS) of MTA in AD.
A total of fifty subjects (25 AD, 25 controls) were included. The neuropsychological tests used were the K-MMSE and the K-ACE. T1 axial imaging visual rating scale (VRS) was applied for assessing the grade of MTA. We calculated the fusion score with the difference of neuropsychological test and VRS of MTA. The receiver operating characteristics (ROC) curve was used to determine optimal cut-off score, sensitivity and specificity of the fusion scores in screening AD.
No significant differences in age, gender and education were found between AD and control group. The values of K-MMSE, K-ACE, CDR, VRS and cognitive function test minus VRS were significantly lower in the AD group than control group. The AUC (Area under the curve), sensitivity and specificity for K-MMSE minus VRS were 0.857, 84% and 80% and for K-ACE minus VRS were 0.884, 80% and 88%, respectively. Those for K-MMSE only were 0.842, 76% and 72% and for K-ACE only were 0.868, 80% and 88%, respectively.
The fusion of the neuropsychological test and VRS suggested clinical usefulness in their easy and superiority over neuropsychological test only. However, this study failed to find any difference. This may be because of small numbers in the study or because there is no true difference.
Annals of Indian Academy of Neurology 03/2013; 16(3):384-387. DOI:10.4103/0972-2327.116951 · 0.60 Impact Factor
"This opens the possibility of using such biomarkers to enrich or stratify the population of clinical trials targeting a prodromal subpopulation of aMCI subjects at a high risk of progression to AD dementia  . Indeed, several groups have shown, in a variety of independent subject cohorts, that measurements derived from structural MRI data       , CSF samples      and FDG-PET   can be predictive of subsequent progression from aMCI to AD dementia. Moreover, Apolipoprotein E (ApoE) genotype, in particular the ε4 allele, has also been shown to be predictive of disease progression  . "
[Show abstract][Hide abstract] ABSTRACT: The goal of this study was to identify the optimal combination of magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) biomarkers to predict conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) dementia within two years, for enriching clinical trial populations. Data from 63 subjects in the Alzheimer's Disease Neuroimaging Initiative aMCI cohort who had MRI and FDG-PET imaging along with CSF data at baseline and at least two years clinical follow-up were used. A Bayesian classification method was used to determine which combination of 31 variables (MRI, FDG-PET, CSF measurements, apolipoprotein E (ApoE) genotype, and cognitive scores) provided the most accurate prediction of aMCI to AD conversion. The cost and time trade-offs for the use of these biomarkers as inclusion criteria in clinical trials were evaluated. Using the combination of all biomarkers, ApoE genotype, and cognitive scores, we achieved an accuracy of 81% in predicting aMCI to AD conversion. With only ApoE genotype and cognitive scores, the prediction accuracy decreased to 62%. By comparing individual modalities, we found that MRI measures had the best predictive power (accuracy = 78%), followed by ApoE, FDG-PET, CSF, and the Alzheimer's disease assessment scale-cognitive subscale. The combination of biomarkers from different modalities, measuring complementary aspects of AD pathology, provided the most accurate prediction of aMCI to AD conversion within two years. This was predominantly driven by MRI measures, which emerged as the single most powerful modality. Overall, the combination of MRI, ApoE, and cognitive scores provided the best trade-off between cost and time compared with other biomarker combinations for patient recruitment in clinical trial.
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