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Creators/Authors contains: "Toga, Arthur W."

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  1. ; ; ; ; ; ; ; ; ; ( , CNS Neuroscience & Therapeutics)
    Abstract Background

    Alzheimer's disease (AD), the most prevalent form of dementia, affects 6.5 million Americans and over 50 million people globally. Clinical, genetic, and phenotypic studies of dementia provide some insights of the observed progressive neurodegenerative processes, however, the mechanisms underlying AD onset remain enigmatic.

     Aims

    This paper examines late‐onset dementia‐related cognitive impairment utilizing neuroimaging‐genetics biomarker associations.

     Materials and Methods

    The participants, ages 65–85, included 266 healthy controls (HC), 572 volunteers with mild cognitive impairment (MCI), and 188 Alzheimer's disease (AD) patients. Genotype dosage data for AD‐associated single nucleotide polymorphisms (SNPs) were extracted from the imputed ADNI genetics archive using sample‐major additive coding. Such 29 SNPs were selected, representing a subset of independent SNPs reported to be highly associated with AD in a recent AD meta‐GWAS study by Jansen and colleagues.

     Results

    We identified the significant correlations between the 29 genomic markers (GMs) and the 200 neuroimaging markers (NIMs). The odds ratios and relative risks for AD and MCI (relative to HC) were predicted using multinomial linear models.

     Discussion

    In the HC and MCI cohorts, mainly cortical thickness measures were associated with GMs, whereas the AD cohort exhibited different GM‐NIM relations. Network patterns within the HC and AD groups were distinct in cortical thickness, volume, and proportion of White to Gray Matter (pct), but not in the MCI cohort. Multinomial linear models of clinical diagnosis showed precisely the specific NIMs and GMs that were most impactful in discriminating between AD and HC, and between MCI and HC.

     Conclusion

    This study suggests that advanced analytics provide mechanisms for exploring the interrelations between morphometric indicators and GMs. The findings may facilitate further clinical investigations of phenotypic associations that support deep systematic understanding of AD pathogenesis.

     
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  2. ; ; ; ; ; ; ; ; ; ; et al ( , Proceedings of the National Academy of Sciences)
    The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N  = 351) and Alzheimer’s disease (AD, N  = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk. 
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  3. ; ; ; ; ; ; ; ; ; ; et al ( , Alzheimer's & Dementia)
    null (Ed.)
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  4. ; ; ; ; ; ; ( , Neuroinformatics)
    Regional morphological analysis represents a crucial step in most neuroimaging studies. Results from brain segmentation techniques are intrinsically prone to certain degrees of variability, mainly as results of suboptimal segmentation. To reduce this inherent variability, the errors are often identified through visual inspection and then corrected (semi)manually. Identification and correction of incorrect segmentation could be very expensive for large-scale studies. While identification of the incorrect results can be done relatively fast even with manual inspection, the correction step is extremely time-consuming, as it requires training staff to perform laborious manual corrections. Here we frame the correction phase of this problem as a missing data problem. Instead of manually adjusting the segmentation outputs, our computational approach aims to derive accurate morphological measures by machine learning imputation. Data imputation techniques may be used to replace missing or incorrect region average values with carefully chosen imputed values, all of which are computed based on other available multivariate informa- tion. We examined our approach of correcting segmentation outputs on a cohort of 970 subjects, which were undergone an extensive, time-consuming, manual post-segmentation correction. A random forest imputation technique recovered the gold standard results with a significant accuracy (r = 0.93, p < 0.0001; when 30% of the segmentations were considered incorrect in a non-random fashion). The random forest technique proved to be most effective for big data studies (N > 250). 
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  5. ; ; ; ; ; ; ; ; ; ; et al ( , NeuroImage)
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  6. ; ; ; ; ; ; ; ; ; ; et al ( , NeuroImage)
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  7. ; ; ; ; ; ; ; ; ; ; et al ( , Scientific Reports)
    Abstract

    In the Alzheimer’s disease (AD) continuum, the prodromal state of mild cognitive impairment (MCI) precedes AD dementia and identifying MCI individuals at risk of progression is important for clinical management. Our goal was to develop generalizable multivariate models that integrate high-dimensional data (multimodal neuroimaging and cerebrospinal fluid biomarkers, genetic factors, and measures of cognitive resilience) for identification of MCI individuals who progress to AD within 3 years. Our main findings were i) we were able to build generalizable models with clinically relevant accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting progression; iii) our methodology allowed us to discover that expression ofCR1(complement receptor 1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive value. This work highlights the value of optimized machine learning approaches for analyzing multimodal patient information for making predictive assessments.

     
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