Identification and Temporal Characterization of Features Associated with the Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

2018 ◽  
Vol 15 (8) ◽  
pp. 751-763 ◽  
Author(s):  
Antonio Martinez-Torteya ◽  
Hugo Gomez-Rueda ◽  
Victor Trevino ◽  
Joshua Farber ◽  
Jose Tamez-Pena ◽  
...  

Background: Diagnosing Alzheimer’s disease (AD) in its earliest stages is important for therapeutic and support planning. Similarly, being able to predict who will convert from mild cognitive impairment (MCI) to AD would have clinical implications. Objectives: The goals of this study were to identify features from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database associated with the conversion from MCI to AD, and to characterize the temporal evolution of that conversion. Methods: We screened the publically available ADNI longitudinal database for subjects with MCI who have developed AD (cases: n=305), and subjects with MCI who have remained stable (controls: n=250). Analyses included 1,827 features from laboratory assays (n=12), quantitative MRI scans (n=1,423), PET studies (n=136), medical histories (n=72), and neuropsychological tests (n=184). Statistical longitudinal models identified features with significant differences in longitudinal behavior between cases and matched controls. A multiple-comparison adjusted log-rank test identified the capacity of the significant predictive features to predict early conversion. Results: 411 features (22.5%) were found to be statistically different between cases and controls at the time of AD diagnosis; 385 features were statistically different at least 6 months prior to diagnosis, and 28 features distinguished early from late conversion, 20 of which were obtained from neuropsychological tests. In addition, 69 features (3.7%) had statistically significant changes prior to AD diagnosis. Conclusion: Our results characterized features associated with disease progression from MCI to AD, and, in addition, the log-rank test identified features which are associated with the risk of early conversion.

2018 ◽  
Vol 11 ◽  
pp. 97-111 ◽  
Author(s):  
Stephanos Leandrou ◽  
Styliani Petroudi ◽  
Panayiotis A. Kyriacou ◽  
Constantino Carlos Reyes-Aldasoro ◽  
Constantinos S. Pattichis

2016 ◽  
Vol 29 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Jordi A. Matias-Guiu ◽  
Ana Cortés-Martínez ◽  
Maria Valles-Salgado ◽  
Teresa Rognoni ◽  
Marta Fernández-Matarrubia ◽  
...  

ABSTRACTBackground:Addenbrooke's Cognitive Examination III (ACE-III) is a screening test that was recently validated for diagnosing dementia. Since it assesses attention, language, memory, fluency, and visuospatial function separately, it may also be useful for general neuropsychological assessments. The aim of this study was to analyze the tool's ability to detect early stages of Alzheimer's disease and to examine the correlation between ACE-III scores and scores on standardized neuropsychological tests.Methods:Our study included 200 participants categorized as follows: 25 healthy controls, 48 individuals with subjective memory complaints, 47 patients with amnestic mild cognitive impairment and 47 mild Alzheimer's disease, and 33 patients with other neurodegenerative diseases.Results:The ACE-III memory and language domains were highly correlated with the neuropsychological tests specific to those domains (Pearson correlation coefficient of 0.806 for total delayed recall on the Free and Cued Selective Reminding Test vs. 0.744 on the Boston Naming Test). ACE-III scores discriminated between controls and patients with amnestic mild cognitive impairment (AUC: 0.906), and between controls and patients with mild Alzheimer's disease (AUC: 0.978).Conclusion:Our results suggest that ACE-III is a useful neuropsychological test for assessing the cognitive domains of attention, language, memory, and visuospatial function. It also enables detection of Alzheimer's disease in early stages.


2003 ◽  
Vol 33 (6) ◽  
pp. 1039-1050 ◽  
Author(s):  
C. A. DE JAGER ◽  
E. HOGERVORST ◽  
M. COMBRINCK ◽  
M. M. BUDGE

Background. Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia.Method. The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with ‘possible’ or ‘probable’ Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann–Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations.Results. The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test.Conclusions. Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.


2019 ◽  
Vol 40 (4) ◽  
pp. 739-746 ◽  
Author(s):  
Willem H Bouvy ◽  
Susanne J van Veluw ◽  
Hugo J Kuijf ◽  
Jaco JM Zwanenburg ◽  
Jaap L Kappelle ◽  
...  

MRI-visible perivascular spaces (PVS) in the semioval centre are associated with cerebral amyloid angiopathy (CAA), but it is unknown if PVS co-localize with MRI markers of CAA. To examine this, we assessed the topographical association between cortical cerebral microbleeds (CMBs) – as an indirect marker of CAA – and dilatation of juxtacortical perivascular spaces (jPVS) in 46 patients with amnestic mild cognitive impairment (aMCI) or early Alzheimer’s disease (eAD). The degree of dilatation of jPVS <1 cm around each cortical CMBs was compared with a similar reference site (no CMB) in the contralateral hemisphere, using a 4-point scale. Also, jPVS dilatation was compared between patients with and without cortical CMBs. Eleven patients (24%) had cortical CMBs [total=35, median=1, range=1–14] of whom five had >1 cortical CMBs. The degree of jPVS dilatation was higher around CMBs than at the reference sites [Wilcoxon signed rank test, Z = 2.2, p = 0.03]. Patients with >1 cortical CMBs had a higher degree of jPVS dilation [median=2.2, IQR = 1.8–2.3] than patients without cortical CMBs [median=1.4, IQR = 1.0–1.8], p = 0.02. We found a topographical association between a high degree of jPVS dilatation and cortical CMBs, supporting a common underlying pathophysiology – most likely CAA.


2020 ◽  
Vol 77 (3) ◽  
pp. 1117-1127
Author(s):  
Anne Katrine Bergland ◽  
Petroula Proitsi ◽  
Bjørn-Eivind Kirsebom ◽  
Hogne Soennesyn ◽  
Abdul Hye ◽  
...  

Background: Lipids have important structural roles in cell membranes and changes to these membrane lipids may influence β- and γ-secretase activities and thus contribute to Alzheimer’s disease (AD) pathology. Objective: To explore baseline plasma lipid profiling in participants with mild cognitive impairment (MCI) with and without AD pathology. Methods: We identified 261 plasma lipids using reversed-phase liquid chromatography/mass spectrometry in cerebrospinal fluid amyloid positive (Aβ+) or negative (Aβ–) participants with MCI as compared to controls. Additionally, we analyzed the potential associations of plasma lipid profiles with performance on neuropsychological tests at baseline and after two years. Results: Sphingomyelin (SM) concentrations, particularly, SM(d43:2), were lower in MCI Aβ+ individuals compared to controls. Further, SM(d43:2) was also nominally reduced in MCI Aβ+ individuals compared to MCI Aβ–. No plasma lipids were associated with performance on primary neuropsychological tests at baseline or between the two time points after correction for multiple testing. Conclusion: Reduced plasma concentrations of SM were associated with AD.


2009 ◽  
Vol 3 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Patrícia Helena Figueirêdo do Vale ◽  
Lívia Spíndola ◽  
Maira Okada de Oliveira ◽  
Cristiane Garcia da Costa Armentano ◽  
Claudia Sellitto Porto ◽  
...  

Abstract Mild Cognitive Impairment (MCI) can be an intermediate state between normality and dementia in some patients. An early diagnosis, through neuropsychological assessment, could identify individuals at risk of developing dementia. Objective: To verify differences in performance on neuropsychological tests among controls, amnestic MCI (aMCI) and Alzheimer’s disease (AD) patients. Methods: Sixty-eight AD patients (mean age 73.77±7.24; mean schooling 9.04±4.83; 40 women and 28 men), 34 aMCI patients (mean age 74.44±7.05; mean schooling 12.35±4.01; 20 women) and 60 controls (mean age 68.90±7.48; mean schooling 10.72±4.74; 42 women) were submitted to a neuropsychological assessment composed of tasks assessing executive functions, language, constructive abilities, reasoning and memory. Results: There were statistically significant differences in performance across all tests among control, aMCI and AD groups, and also between only controls and AD patients. On comparing control and aMCI groups, we found statistically significant differences in memory tasks, except for immediate recall of Visual Reproduction. There were also statistically significant differences between aMCI and AD groups on tasks of constructive and visuoperceptual abilities, attention, language and memory, except for delayed recall of Visual Reproduction. Conclusions: Neuropsychological assessment was able to discriminate aMCI from AD patients in almost all tests except for delayed recall of Visual Reproduction, visual organization (Hooper) and executive functions (WCST); and discriminate controls from AD patients in all tests, and controls from aMCI patients in all memory tests except for immediate recall of Visual Reproduction.


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