scholarly journals A simple classification framework for predicting Alzheimer’s disease from region-based grey matter volume and APOE genotype status

2020 ◽  
Vol 8 (2) ◽  
pp. 15
Author(s):  
Reyhaneh Ghoreishiamiri ◽  
Graham Little ◽  
Matthew R. G. Brown ◽  
Russell Greiner

Alzheimer’s Disease (AD) is a prevalent neurodegenerative disease currently affecting more than 47 million people in the world. There are now many complex classifiers that can accurately distinguish AD patients from healthy controls, based on the subject’s structural magnetic resonance imaging (MRI) brain scan. Most such automated diagnostic systems are blackboxes: While their predictions are accurate, it is difficult for clinicians to interpret those predictions, due to the large number of features used by the classifier, and/or by the complexity of that classifier. This work demonstrates that an automated learning algorithm can produce a simple classifier that can correctly distinguish AD patients from healthy controls (HC) similar to its more-complex counterparts. Here we buildthis classifier from the data in the Alzheimer’s Disease Neuroimaging Initiative database, using a fairly small set of features, including grey matter volumes of 33 regions of interest derived from structural MRI, as well as the APOE genotype. We first considered three simple base-learners that each produce a classifier that is simple and interpretable. Running our overall learner, involving standard feature selection processes and these simple base-learners, on these features, produced a 7-feature elastic net model, EN7, that achieved accuracy of 89.28% on the test set. Next, we ran the same overall learner using two more-complex base-learners over the same initial dataset. The accuracy of the best model here was 90.47%, which was not statistically different from the performance of our much simpler EN7 model.

2013 ◽  
Vol 9 ◽  
pp. P426-P427
Author(s):  
David Cash ◽  
Gerard Ridgway ◽  
Natalie Ryan ◽  
Yuying Liang ◽  
Kirsi Kinnunen ◽  
...  

2020 ◽  
Vol 10 (2) ◽  
pp. 32 ◽  
Author(s):  
Simon M. Bell ◽  
Matteo De Marco ◽  
Katy Barnes ◽  
Pamela J. Shaw ◽  
Laura Ferraiuolo ◽  
...  

Alzheimer’s disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate with neuropsychological changes. Fibroblasts were taken from 10 AD patients and 10 controls. Metabolic assessment included measuring total cellular ATP, extracellular lactate, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolytic function. All participants were assessed with neuropsychological testing and brain structural MRI. AD patients had significantly lower scores in delayed and immediate recall, semantic memory, phonemic fluency and Mini Mental State Examination (MMSE). AD patients also had significantly smaller left hippocampal, left parietal, right parietal and anterior medial prefrontal cortical grey matter volumes. Fibroblast MMP, mitochondrial spare respiratory capacity (MSRC), glycolytic reserve, and extracellular lactate were found to be lower in AD patients. MSRC/MMP correlated significantly with semantic memory, immediate and delayed episodic recall. Correlations between MSRC and delayed episodic recall remained significant after controlling for age, education and brain reserve. Grey matter volumes did not correlate with MRSC/MMP. AD fibroblast metabolic assessment may represent an emergent disease biomarker of AD.


2013 ◽  
Vol 9 ◽  
pp. P45-P46
Author(s):  
David Cash ◽  
Gerard Ridgway ◽  
Natalie Ryan ◽  
Yuying Liang ◽  
Kirsi Kinnunen ◽  
...  

Brain ◽  
2020 ◽  
Vol 143 (2) ◽  
pp. 635-649 ◽  
Author(s):  
Alexa Pichet Binette ◽  
Julie Gonneaud ◽  
Jacob W Vogel ◽  
Renaud La Joie ◽  
Pedro Rosa-Neto ◽  
...  

Abstract Age being the main risk factor for Alzheimer’s disease, it is particularly challenging to disentangle structural changes related to normal brain ageing from those specific to Alzheimer’s disease. Most studies aiming to make this distinction focused on older adults only and on a priori anatomical regions. Drawing on a large, multi-cohort dataset ranging from young adults (n = 468; age range 18–35 years), to older adults with intact cognition (n = 431; age range 55–90 years) and with Alzheimer’s disease (n = 50 with late mild cognitive impairment and 71 with Alzheimer’s dementia, age range 56–88 years), we investigated grey matter organization and volume differences in ageing and Alzheimer’s disease. Using independent component analysis on all participants’ structural MRI, we first derived morphometric networks and extracted grey matter volume in each network. We also derived a measure of whole-brain grey matter pattern organization by correlating grey matter volume in all networks across all participants from the same cohort. We used logistic regressions and receiver operating characteristic analyses to evaluate how well grey matter volume in each network and whole-brain pattern could discriminate between ageing and Alzheimer’s disease. Because increased heterogeneity is often reported as one of the main features characterizing brain ageing, we also evaluated interindividual heterogeneity within morphometric networks and across the whole-brain organization in ageing and Alzheimer’s disease. Finally, to investigate the clinical validity of the different grey matter features, we evaluated whether grey matter volume or whole-brain pattern was related to clinical progression in cognitively normal older adults. Ageing and Alzheimer’s disease contributed additive effects on grey matter volume in nearly all networks, except frontal lobe networks, where differences in grey matter were more specific to ageing. While no networks specifically discriminated Alzheimer’s disease from ageing, heterogeneity in grey matter volumes across morphometric networks and in the whole-brain grey matter pattern characterized individuals with cognitive impairments. Preservation of the whole-brain grey matter pattern was also related to lower risk of developing cognitive impairment, more so than grey matter volume. These results suggest both ageing and Alzheimer’s disease involve widespread atrophy, but that the clinical expression of Alzheimer’s disease is uniquely associated with disruption of morphometric organization.


2007 ◽  
Vol 34 (10) ◽  
pp. 1658-1669 ◽  
Author(s):  
Miharu Samuraki ◽  
Ichiro Matsunari ◽  
Wei-Ping Chen ◽  
Kazuyoshi Yajima ◽  
Daisuke Yanase ◽  
...  

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Peter Hermann ◽  
Anna Villar-Piqué ◽  
Matthias Schmitz ◽  
Christian Schmidt ◽  
Daniela Varges ◽  
...  

Abstract Background Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer’s disease (p = 0.013). Conclusions Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers.


2020 ◽  
Vol 17 (7) ◽  
pp. 667-679
Author(s):  
Matteo De Marco ◽  
Riccardo Manca ◽  
Janine Kirby ◽  
Guillaume M. Hautbergue ◽  
Daniel J. Blackburn ◽  
...  

Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers. Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants. Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.


2015 ◽  
Vol 46 (1) ◽  
pp. 167-178 ◽  
Author(s):  
Lubov E. Zeifman ◽  
William F. Eddy ◽  
Oscar L. Lopez ◽  
Lewis H. Kuller ◽  
Cyrus Raji ◽  
...  

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