Eben S. Schwartz's research while affiliated with Dartmouth–Hitchcock Medical Center and other places

Publications (29)

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For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade of Aβ- and tau-related processes. Therefore, we set out to investigate how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline acros...
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Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This...
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Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological ch...
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Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected 18F-fluorodeoxyglucose (18F-FDG) PET brain images from two independent cohorts: the Alzheimer’s Disease Neuroimagin...
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The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we ai...
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Alzheimer’s disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in 18F-flortaucipir vs. 18F-fluorodeoxyglucose positron emission tomo...
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Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a semi-supervised deep-clustering method, which examines neuroanatomical heterogeneity contrasted against normal brain structure, to identify disease subtypes through neuro...
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Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of A...
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Klotho-VS heterozygosity (KL-VS het ) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VS het is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VS het and levels of beta-amyloid, a key...
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Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we ident...
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In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional conne...
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There is well-documented evidence of brain network differences between individuals with Alzheimer’s disease (AD) and healthy controls (HC). To date, imaging studies investigating brain networks in these populations have typically been cross-sectional, and the reproducibility of such findings is somewhat unclear. In a novel study, we use the longitu...
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Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and...
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This study was designed to develop performance validity indicators embedded within the Delis-Kaplan Executive Function Systems (D-KEFS) version of the Stroop task. Archival data from a mixed clinical sample of 132 patients (50% male; MAge= 43.4; MEducation= 14.1) clinically referred for neuropsychological assessment were analyzed. Criterion measure...
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Objectives: The Forced Choice Recognition (FCR) trial of the California Verbal Learning Test, 2nd edition, was designed as an embedded performance validity test (PVT). To our knowledge, this is the first systematic review of classification accuracy against reference PVTs. Methods: Results from peer-reviewed studies with FCR data published since...
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Deficits in contrast sensitivity (CS) have been reported in Alzheimer's disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n...
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Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the...
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Full-text available
Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the...
Article
Full-text available
Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the...
Article
Full-text available
Personality assessment is a potentially important component of clinical and empirical work with neurological patients because (a) individual differences in personality may be associated with different neurological outcomes and (b) central nervous system changes may give rise to alteration in personality. For personality assessment to be useful to c...
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Multiple sclerosis (MS) is a disease of the central nervous system where roughly 50% of patients exhibit cognitive impairment. Episodic memory defects are particularly common in MS and the California Verbal Learning Test: 2nd Edition (CVLT-II) was recommended for assessment in MS in a recently published consensus position paper. We investigated the...
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Patients diagnosed with multiple sclerosis (MS) are believed to undergo personality changes, which could have implications for how they perceive themselves and are perceived by others. We endeavored to examine the extent to which patients' self-perceptions are congruent with how they are perceived by significant others across five trait domains as...

Citations

... Our statical models suggested that the APOEε4-dependent Aβ effects on longitudinal tau deposition were mediated by the concentrations of p-tau217 + . Although this suggest potential causal relationships that are accordance with previously proposed biological models of disease progression 27,38,39 , mechanistic studies are needed to examine this further. Finally, future multicenter studies with longer follow-up intervals and multiple time points are needed to better characterize the temporal relationships between APOEε4, Aβ, and tau across the AD spectrum. ...
... In addition, three genes were identified in a sex-stratified genome-wide association study that was associated with tau (osteocrine and claudin-16) and amyloid-β (serpin family B member 1) only in the brain of women [88]. Furthermore, several other genes have been identified recently such as Kdm6a [89], MGMT variants [90], ubiquitin-specific peptidase 11 [91], and St2 [92]. A full understanding of the role these genes in AD requires further study. ...
... The hippocampus is also known to be affected at the earliest stages of MCI, even before a diagnosis can be made (Braak and Braak, 1995), and hippocampal atrophy has been found to affect the progression of AD only in females (Burke et al., 2019). Recent research revealed additional brain imaging markers that may also contribute to the sex differences in AD and are specifically present in individuals with MCI and that reduced hippocampal volume and any microhemorrhage, regardless of location, are the best MRI features to predict the transition from pre-MCI to MCI Jiang et al., 2022). Cavedo et al. (2018) found that males with MCI had a higher anterior cingulate cortex amyloid load and glucose hypometabolism in the precuneus, posterior cingulate, and inferior parietal cortex. ...
... Epigenetic age acceleration or deceleration is defined as an increase or decrease in epigenetic age compared to chronological age. Accumulating evidence has shown that epigenetic age acceleration is associated with numerous risk factors and outcomes for psychiatric disorders, including adversity exposure [16][17][18], cognitive decline [19][20][21], altered brain structures [22][23][24][25], and depression [26][27][28]. However, previous studies have shown inconsistent results in SCZ. ...
... Alzheimer's disease (AD) involves cognitive impairment with substantial betweenpatient variability in clinical presentation as well as the burden and distribution of pathology. Such clinicopathologic heterogeneity is both challenges and opportunities for carrying out systematic and biomarker-based studies to refine our understanding of AD biology, diagnosis, and management (Duong et al., 2022). AD has complex pathophysiological mechanisms which are not completely understood. ...
... Various commonly obtained imaging measurements such as volumes of brain structures, cortical thickness, or strength of functional networks lack specificity by virtue of being affected by multiple such pathologies. Methods for disentangling such heterogeneity [11][12][13][14][15] can enable precision diagnostics and disease subtyping by identifying the type and extent of pathologic processes that actively influence an individual's brain phenotype. ...
... We also found that the hold-out test dataset outperformed the training dataset in the brain volume model after brain age correction. Similar results could be found in previous brain age studies 13,34,37 . In this study, we randomly divided 330 healthy controls into the training and test datasets in a ratio of 7 to 3. ...
... Due to its direct correlation with tissue atrophy and cognitive symptoms in Alzheimer's disease, tau pathology is a specifically interesting target for modeling, as it bears high potential for the prediction of disease progression timelines and the evaluation of potential future treatments. Several studies have focused on models for tau pathology and their validation with cross-sectional or longitudinal patient data [17][18][19]. We have previously proposed a network diffusion model to simulate misfolded tau protein propagation and shown that it can capture individual patient pathology by learning its model parameters from tau PET data of 76 subjects using Bayesian inference [20]. ...
... Although genetic polymorphisms such as APOE genotype are often viewed holistically, the relative expression of genes including APOE varies in different brain regions (35,36). The availability of gene expression data such as the Allen Human Brain Atlas (AHBA) now makes it possible to relate AD pathology observed using neuroimaging to underlying topologies of genetic expression that they may reflect (35)(36)(37)(38)(39)(40). ...
... Updated versions expand the models' applicability to include the personalized discriminative event-based model [88] and the kernel density estimation event-based model [89], with applications including typical and atypical Alzheimer's disease [86,88,89], multiple sclerosis [90], Huntington's disease [91], Parkinson's disease [92] and frontotemporal dementia [93]. The subtype and stage inference (SuStaIn) algorithm [94] combines unsupervised learning with pseudo-time disease progression modelling to automatically estimate disease progression subtypes, with early applications unravelling heterogeneity in Alzheimer's, frontotemporal dementia [94,95] and predicting clinical trial treatment response in multiple sclerosis [96]. ...