Medial Temporal Atrophy Scores Research Articles

Visual Rating of Posterior Atrophy asaMarker of Progression to Dementia inMild Cognitive Impairment Patients.

Although medial temporal atrophy (MTA) is a useful imaging marker of the progression to dementia in mild cognitive impairment (MCI), substantial numbers of MCI patients without MTA still progress to dementia. We investigated whether visual ratings of posterior atrophy (PA) on magnetic resonance imaging show independent predictive value for the progression to dementia in MCI patients. This was a retrospective cohort study of elderly patients who visited Seoul National University Bundang Hospital between 2004 and 2012. A total of 148 patients who were initially diagnosed with MCI were followed for up to 3 years (median 22 months) to determine whether they progressed to dementia. We used 4-point and 5-point visual rating scales to assess PA and MTA, respectively. PA and MTA scores were dichotomized into normal (no atrophy) or abnormal (atrophy) in each patient. We performed a Cox regression analysis to examine the hazard ratios (HRs) of PA and MTA for the progression to dementia with adjustment for age, APOEɛ4 allele status, and baseline Mini-Mental State Examination score. Among the study population, 47 patients progressed to dementia. Visual assessment of the MRI scans revealed that 67 patients (45.3%) showed PA, whereas 85 patients (57.3%) showed MTA. The HRs with 95% confidence intervals for PA and MTA were 2.516 (1.244-5.091) and 4.238 (1.680-10.687), respectively. The predictive values of visually assessed PA and MTA remained significant, independent of the covariates. Visual assessment of PA has independent predictive value for progression to dementia in MCI patients.

Posterior Atrophy and Medial Temporal Atrophy Scores Are Associated with Different Symptoms in Patients with Alzheimer's Disease and Mild Cognitive Impairment.

BackgroundWhether 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.MethodsPatients 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.ResultsWe 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).ConclusionRegional atrophy is related to different symptoms in patients with AD or MCI. PA score is useful as a complementary measure for non-cognitive symptom.

Metal-Score as a Potential Non-Invasive Diagnostic Test for Alzheimer’s Disease

The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls. All subjects underwent biochemical, neuroimaging and cognitive evaluations. Significant differences were observed among the tested groups for the levels of copper, free copper, peroxides, and TAS and for the Cp/Tf with disparity in couple comparison. On this basis we created the M-score as linear combination of biometal variables and APOE genotype. Besides its ability to discriminate AD patients vs. controls (ROC AUC=90%), M-score was able to distinguish AD vs. VaD (ROC AUC=79%). Moreover, we calculated the sensitivity and the specificity for M-score and for the other significant variables: M-score reached the highest sensitivity without a relevant loss in terms of specificity. When we compared M-score with APOE genotype and Medial Temporal Atrophy score, it resulted statistically better than these diagnostic markers. In conclusion, we confirm the link between biometals and AD and suggest its potential as diagnostic tool. Further studies may elucidate its potential role as reliable diagnostic test.

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and PurposeIt was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer's disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD.MethodsOf 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology.ResultsThe MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA.ConclusionsOur findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.

Discriminating MCI subjects who will decline to Alzheimer's disease from controls: SVM versus medial temporal atrophy lobe rating

Mild cognitive impairment (MCI) patients progress to a diagnosis of probable Alzheimer's disease (AD) at a rate of ∼10-15% per year. Medial temporal atrophy (MTA) is a marker of AD and risk of progression that has been included in proposed diagnostic criteria for pre-dementia AD. We aimed to test whether rating MTA or an automated method of analysing grey matter patterns of atrophy using baseline MRI scans was more accurate in discriminating MCI patients who convert to AD from controls. 13 patients with MCI at baseline and a later diagnosis of AD (MCI converters) (mean age 66 years at baseline) and 29 controls (mean age 63 years) were included. Each subject had a single volumetric MRI scan at baseline, and was followed for 36 months. Voxel based morphometry (VBM) was used to analyse the grey matter volume differences at baseline. Following this a multivariate analysis of grey matter volume was made in a leave-one-out fashion using support vector machines (SVM). This enabled the assessment of accuracy for discriminating MCI converters from controls. Additionally each scan was rated (0-4) for left and right MTA using Scheltens’ scale. The average of left and right MTA rating was used with a cut-off value of MTA rating =1.5 to dichotomise these average scores. Using the dichotomised scores the accuracy of group discrimination simply using MTA was calculated. The area under the receiver operator curve (AUC) was also calculated for each method. Dichotomised MTA scores had an accuracy of predicting MCI conversion to AD from controls of 83% (AUC =0.87), compared to that of 67% (AUC=0.54) using SVM. This small study suggests that MTA rating better discriminates MCI subjects who subsequently convert to clinical AD from controls compared with an SVM technique based on grey matter throughout the whole image.

Diffusion-weighted ASPECTS as an independent marker for predicting functional outcome

Whether lesion volume on diffusion-weighted MRI imaging (DWI) can reliably predict functional outcome in acute ischemic stroke is controversial. The aim of our study was to assess whether the Alberta Stroke Program Early CT Score (ASPECTS) on DWI is useful for predicting functional outcome in patients with anterior circulation infarction with a broad range of severities. Three-hundred and fifty patients with first-ever ischemic stroke in the anterior circulation within 24 h of onset were enrolled. We compared background characteristics, vital signs, laboratory data, and MRI findings between favorable (F) and unfavorable (U) outcome groups at 3 months, according to the modified Rankin Scale (mRS). The F and U groups were defined as having a mRS of 0-2 and 3-6, respectively. DWI ASPECTS was scored by DWI obtained 3-24 h after onset. Two-hundred and eighteen patients (62.3%) were classified into the F group and 132 patients (37.7%) into the U group. On univariate analysis, the F group patients were younger, had lower score of the National Institutes of Health Stroke Scale (NIHSS) at entry (5.7 ± 3.3 vs. 14.2 ± 6.0), male predominance, longer time after onset, lower rate of prior antithrombotic therapy, higher hematocrit and lower fibrinogen than the U group patients. Stroke subtype was different between the two groups, and F group patients had higher DWI ASPECTS score, lower leukoaraiosis and medial temporal atrophy score, and lower rate of early neurological deterioration (END) than the U group patients. Multiple logistic regression analysis revealed that NIHSS (p < 0.001), prior antithrombotic therapy (p = 0.013), ASPECTS (p = 0.002), and END (p < 0.001) were independent predictors of functional outcome. DWI ASPECTS can be an independent predictor for functional outcome, along with other clinical variables.

Reliability and Validity of an Algorithm for the Diagnosis of Normal Cognition, Mild Cognitive Impairment, and Dementia: Implications for Multicenter Research Studies

The traditional consensus diagnosis (ConsDx) of normal cognition, mild cognitive impairment (MCI), and dementia relies on the reconciliation of an informant-based report of cognitive and functional impairment by a physician diagnosis (PhyDx), and a neuropsychological diagnosis (NPDx). As this procedure may be labor intensive and influenced by the philosophy and biases of a clinician, the diagnostic algorithm (AlgDx) was developed to identify individuals as cognitively normal, with MCI, or dementia. The AlgDx combines the PhyDx with the NPDx, using a diagnostic algorithm that provides cognitive diagnoses, as defined by the National Alzheimer Coordinating Center/Uniform Data Set nomenclature. Reliability of the AlgDx was assessed in 532 community-dwelling elderly subjects by its concordance with the ConsDx and association with two biomarkers, medial temporal atrophy (MTA) scores of brain magnetic resonance imaging scans, and Apolipoprotein E (ApoE)-epsilon4 genotype. A high degree of concordance was observed between ConsDx and AlgDx with a weighted Cohen's kappa of 0.84. Concordance of the AlgDx to the same ConsDx categories ranged from 85% to 92%. Excellent discriminative validity was observed using AlgDx, MTA scores, and ApoE-epsilon4 allele frequencies, each of which distinguished subjects with amnestic MCI and dementia from normal subjects. The AlgDx of normal cognition, MCI, and dementia is a valid alternative that reduces time, effort, and biases associated with the ConsDx. The inherent reliability of a fixed algorithm, together with its efficiency and avoidance of individual bias, suggests the AlgDx may be used in longitudinal, multisite clinical trials, and population studies of MCI and dementia.

Posterior circulation ASPECTS on diffusion-weighted MRI can be a powerful marker for predicting functional outcome

There are few studies regarding functional outcome and lesion extent on diffusion-weighted MRI (DWI) in patients with posterior circulation (PC) infarction. The aim of our study was to assess whether a newly proposed posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) on DWI is useful for predicting functional outcome in PC patients. One hundred thirty-two patients with first-ever ischemic stroke in the posterior circulation within 24 h of onset who were admitted to our hospital were enrolled in the study. We compared background characteristics, vital signs, laboratory data, and MRI findings between favorable (F) and unfavorable (U) outcome groups at 3 months, according to the modified Rankin Scale (mRS). The F and U groups were defined as having a mRS of 0-2 and 3-6, respectively. pc-ASPECTS was scored by DWI obtained 12-36 h after onset. Ninety-eight patients (74.2%) were classified into the F group and 34 patients (25.8%) into the U group. On univariate analysis, F group patients were younger, had lower National Institutes of Health Stroke Scale (NIHSS) score at entry, and a lower rate of early neurological deterioration (END) and cardioembolic stroke than U group patients. On MRI, F group patients had lower leukoaraiosis and medial temporal atrophy score and higher pc-ASPECTS score on DWI compared to U group patients. Multiple logistic regression analysis revealed NIHSS (p < 0.001), END (p = 0.0057), pc-ASPECTS (p < 0.001), and leukoaraiosis (p = 0.0091) as independent predictors of functional outcome. pc-ASPECTS appears to be a powerful marker for predicting functional outcome, along with clinical severity and END. Leukoaraiosis may also be an independent predictor of functional outcome.

Association of White Matter Hyperintensity Measurements on Brain MR Imaging with Cognitive Status, Medial Temporal Atrophy, and Cardiovascular Risk Factors

White matter hyperintensities (WMHs) are frequently characterized as markers of cerebrovascular disease, whereas medial temporal atrophy (MTA) is a recognized marker of Alzheimer disease (AD). Our purpose was to test the reliability of a visual rating system (VRS) in evaluating WMHs and MTA and in distinguishing healthy from cognitively impaired subjects. Subjects (n = 192) enrolled in the Florida Alzheimer's Disease Research Center were diagnosed with no cognitive impairment, nonamnestic mild cognitive impairment (na-MCI), amnestic MCI (a-MCI), or probable AD. The severity of WMHs was assessed on T2-weighted fluid-attenuated inversion recovery axial MR images, and the severity of MTA was evaluated on 1.5-mm-thick coronal MR images by using a computer-based visual rating system. Cardiovascular risk factor scores were calculated as the sum of 10 independent cardiovascular risk factors. WMH and MTA scores were greater in subjects with probable AD, relative to those with no cognitive impairment and na-MCI. MTA scores differentiated subjects with a-MCI from those with no cognitive impairment and na-MCI. The total WMH score was significantly related to MTA (r = 0.39; P < .001) but not to cardiovascular risk factor scores (r = 0.07; P = not significant). The overall correct classification rate of probable AD versus no cognitive impairment by using MTA scores was 81.8%, improving to 86.5% when combined with WMH scores. Both MTA and WMH scores distinguished subjects with no cognitive impairment and probable AD. Combining MTA and WMH scores improved the correct classification rate, whereas WMH scores were significantly related to MTA scores, but not to cardiovascular risk factor scores. This finding suggests that among subjects with a-MCI and probable AD, WMHs on MR images are primarily associated with neurodegenerative disease.

Diagnosis and staging of mild cognitive impairment, using a modification of the clinical dementia rating scale: the mCDR

To examine the reliability and validity of the mCDR, a modified version of the clinical dementia rating (CDR) scale. The mCDR is an informant-based, technician-administered, structured interview with multiple choice responses, which does not include objective cognitive testing. Subjects (n = 556) with no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI), and dementia were assessed with mCDR, CDR, and neuropsychological evaluation, while medial temporal atrophy (MTA) was measured on MRI scans. The mCDR and CDR were compared with respect to inter-rater reliability, validity, and ability to predict progression in cognitive diagnosis at 12 month follow-up. The mCDR can be administered in less than one third of the time required to administer the CDR (30 min). Inter-rater reliability (Cohen's weighted kappa) was 0.86 for the mCDR and 0.56 for the CDR. Ability to distinguish between NCI, aMCI, and Dementia subjects, and correlations to memory and non-memory measures were marginally better for the CDR, in comparison to the mCDR. Correlations of mCDR and CDR scores to MTA scores did not differ. Baseline mCDR scores predicted transition from NCI to aMCI, whereas baseline CDR scores predicted transition from aMCI to Dementia. The mCDR, as compared to the CDR, is briefer and more reliable, and is a valid measure of functional ability among subjects with normal cognition, mild cognitive impairment, and mild dementia. The mCDR should be particularly useful as a reliable and economical instrument for assessing change in functional abilities, especially in multi-center clinical trials and population studies of MCI and mild dementia.

The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium

Background In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). Methods Seven academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid, and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater by using visual rating scales. Results Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioral, and neuropsychological features of the European subjects were very similar to their U.S. counterparts. Three-dimensional T1-weighted MRI sequences were successfully performed on all subjects, and cerebrospinal fluid samples were obtained from 77%, 68%, and 83% of AD patients, MCI patients, and controls, respectively. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI patients (0.9, 0.8) to AD patients (2.3, 2.0), whereas mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US-ADNI subjects. Conclusions Academic EADC centers can adopt the ADNI platform to enroll MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US-ADNI.

Qualitative Estimates of Medial Temporal Atrophy as a Predictor of Progression From Mild Cognitive Impairment to Dementia

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.

Anaemia in the elderly.

<h3>Background and Objectives</h3> The ATN framework has been developed to categorize biological processes within the Alzheimer disease (AD) continuum. Because AD pathology often coincides with dementia with Lewy bodies (DLB), we aimed to investigate the distribution of ATN profiles in DLB and associate ATN profiles in DLB with prognosis. <h3>Methods</h3> We included 202 patients with DLB from the Amsterdam Dementia Cohort (68±7 years; 19% female; Mini-Mental State Examination 24 ± 3; abnormal DAT-SPECT 105/119). Patients were classified into 8 profiles according to the ATN framework, using CSF β-amyloid (Aβ)₄₂ (A), CSF p-tau (T), and medial temporal atrophy scores (N). We compared presence of clinical symptoms in ATN profiles and used linear mixed models to analyze decline on cognitive tests (follow-up 3±2 years for n = 139). Mortality risk was assessed using Cox proportional hazards analysis. Analyses were performed on the 8 profiles as well as 3 clustered categories (normal AD biomarkers, non-AD pathologic change, and AD continuum). <h3>Results</h3> Fifty (25%) patients with DLB had normal AD biomarkers (A–T–N–), 37 (18%) had non-AD pathologic change (A−T+N− 10%, A−T−N+ 6%, A−T+N+ 3%), and 115 (57%) were classified within the AD continuum (A+T−N− 20%, A+T+N− 16%, A+T−N+ 10%, A+T+N+ 9%). A+T+N+ patients were older and least often had REM sleep behavior disorder symptoms. Parkinsonism was more often present in A+T− compared to A−T+ patients (independent of N). Compared to patients with normal AD biomarkers, patients in A+ categories showed steeper decline on memory tests and higher mortality risk. Cognitive decline and mortality did not differ between non-AD pathologic change and normal AD biomarkers. <h3>Discussion</h3> In our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD continuum had steeper cognitive decline and shorter survival. Implementing the ATN framework within patients with DLB aids in subtyping patients based on underlying biological processes and could provide targets for future treatment strategies (for example, AD-modifying treatment). Expanding the framework by incorporating markers for α-synucleinopathy would improve the use of the framework to characterize patients with dementia with mixed pathology, which could enhance proper stratification of patients for therapeutic trials.