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Article ; Online: Paving the Way for Alzheimer's Disease Prevention: A Systematic Review of Global Open-Access Neuroimaging Datasets in Healthy Individuals.

Ly, Maria / Yu, Gary Z / Chwa, Won Jong / Raji, Cyrus A

2023 Volume 96, Issue 4, Page(s) 1441–1451

Abstract: Background: Given the advent of large-scale neuroimaging data-driven endeavors for Alzheimer's disease, there is a burgeoning need for well-characterized neuroimaging databases of healthy individuals. With the rise of initiatives around the globe for ... ...

Abstract	Background: Given the advent of large-scale neuroimaging data-driven endeavors for Alzheimer's disease, there is a burgeoning need for well-characterized neuroimaging databases of healthy individuals. With the rise of initiatives around the globe for the rapid and unrestricted sharing of data resources, there is now an abundance of open-source neuroimaging datasets available to the research community. However, there is not yet a systematic review that fully details the demographic information and modalities actually available in all open access neuroimaging databases around the globe. Objective: This systematic review aims to provide compile a list of MR structural imaging databases encompassing healthy individuals across the lifespan. Methods: In this systematic review, we searched EMBASE and PubMed until May 2022 for open-access neuroimaging databases containing healthy control participants of any age, race, with normal development and cognition having at least one structural T1-weighted neuroimaging scan. Results: A total of 403 databases were included, for up to total of 48,268 participants with all available demographic information and imaging modalities detailed in Supplementary Table 1. There were significant trends noted when compiling normative databases for this systematic review, notably that 11.7% of databases included reported ethnicity in their participants, with underrepresentation of many socioeconomic groups globally. Conclusions: As efforts to improve primary prevention of AD may require a broader perspective including increased relevance of earlier stages in life, and strategies in addressing modifiable risk factors may be individualized to specific demographics, improving data characterization to be richer and more rigorous will greatly enhance these efforts.
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/prevention & control ; Neuroimaging/methods ; Magnetic Resonance Imaging ; Cognition ; Risk Factors ; Brain/diagnostic imaging
Language	English
Publishing date	2023-11-12
Publishing country	Netherlands
Document type	Systematic Review ; Research Support, N.I.H., Extramural
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230738
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Article ; Online: Brain PET Imaging: Frontotemporal Dementia.

Ward, Joshua / Ly, Maria / Raji, Cyrus A

PET clinics

2022 Volume 18, Issue 1, Page(s) 123–133

Abstract: Brain PET adds value in diagnosing neurodegenerative disorders, especially frontotemporal dementia (FTD) due to its syndromic presentation that overlaps with a variety of other neurodegenerative and psychiatric disorders. 18F-FDG-PET has improved ... ...

Abstract	Brain PET adds value in diagnosing neurodegenerative disorders, especially frontotemporal dementia (FTD) due to its syndromic presentation that overlaps with a variety of other neurodegenerative and psychiatric disorders. 18F-FDG-PET has improved sensitivity and specificity compared with structural MR imaging, with optimal diagnostic results achieved when both techniques are utilized. PET demonstrates superior sensitivity compared with SPECT for FTD diagnosis that is primarily a supplement to other imaging and clinical evaluations. Tau-PET and amyloid-PET primary use in FTD diagnosis is differentiation from Alzheimer disease, although these methods are limited mainly to research settings.
MeSH term(s)	Humans ; Frontotemporal Dementia/diagnostic imaging ; Brain/diagnostic imaging ; Alzheimer Disease/diagnostic imaging ; Tomography, Emission-Computed, Single-Photon ; Positron-Emission Tomography
Language	English
Publishing date	2022-11-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2764575-7
ISSN	1879-9809 ; 1556-8598
ISSN (online)	1879-9809
ISSN	1556-8598
DOI	10.1016/j.cpet.2022.09.010
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Article ; Online: Advances and Barriers for Clinical Neuroimaging in Late-Life Mood and Anxiety Disorders.

Ly, Maria / Andreescu, Carmen

Current psychiatry reports

2018 Volume 20, Issue 1, Page(s) 7

Abstract: Purpose of review: Mood and anxiety disorders are very commonly experienced by older adults and are becoming a growing concern due to the rapidly aging global population. Recent advances in neuroimaging may help in improving outcomes in late-life mood ... ...

Abstract	Purpose of review: Mood and anxiety disorders are very commonly experienced by older adults and are becoming a growing concern due to the rapidly aging global population. Recent advances in neuroimaging may help in improving outcomes in late-life mood and anxiety disorders. The elucidation of mechanisms contributing to late-life mental health disorders may ultimately lead to the identification of novel therapeutic interventions. Alternatively, clinically validated imaging biomarkers may allow for the prediction of treatment response and identification of better therapeutic approaches in late-life mood and anxiety disorders. Recent findings: In community samples, late-life depression and late-life generalized anxiety disorder occur up to 38 and 15%, respectively, while late-life bipolar disorder is less common and occur in approximately 0.5% of the population. There are significant challenges in treating and improving outcome in late-life mood and anxiety disorders. Time to treatment response and treatment resistance are increased in older adults. Novel neuroimaging techniques have the potential to improve diagnostic and therapeutic outcome in late-life mood and anxiety disorders either through "personalized pharmacotherapy" or through identifying dysfunction regions/networks to be subsequently used for direct interventions such as transcranial magnetic stimulation. This review will provide an overview of recent literature that substantiates the potential role of neuroimaging in clinical practice, as well as the barriers that must be overcome prior to clinical translation.
MeSH term(s)	Aged ; Anxiety Disorders/diagnostic imaging ; Bipolar Disorder/diagnosis ; Brain/diagnostic imaging ; Depressive Disorder/diagnostic imaging ; Geriatric Assessment/methods ; Humans ; Mood Disorders/diagnostic imaging ; Neuroimaging/methods
Language	English
Publishing date	2018-03-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2055376-6
ISSN	1535-1645 ; 1523-3812
ISSN (online)	1535-1645
ISSN	1523-3812
DOI	10.1007/s11920-018-0870-6
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Article ; Online: Overview of MR Imaging Volumetric Quantification in Neurocognitive Disorders.

Raji, Cyrus A / Ly, Maria / Benzinger, Tammie L S

Topics in magnetic resonance imaging : TMRI

2019 Volume 28, Issue 6, Page(s) 311–315

Abstract: This review article provides a general overview on the various methodologies for quantifying brain structure on magnetic resonance images of the human brain. This overview is followed by examples of applications in Alzheimer dementia and mild cognitive ... ...

Abstract	This review article provides a general overview on the various methodologies for quantifying brain structure on magnetic resonance images of the human brain. This overview is followed by examples of applications in Alzheimer dementia and mild cognitive impairment. Other examples will include traumatic brain injury and other neurodegenerative dementias. Finally, an overview of general principles for protocol acquisition of magnetic resonance imaging for volumetric quantification will be discussed along with the current choices of FDA cleared algorithms for use in clinical practice.
MeSH term(s)	Algorithms ; Brain/diagnostic imaging ; Brain/pathology ; Brain Diseases/diagnostic imaging ; Brain Diseases/pathology ; Humans ; Magnetic Resonance Imaging/methods
Language	English
Publishing date	2019-12-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1112716-8
ISSN	1536-1004 ; 0899-3459
ISSN (online)	1536-1004
ISSN	0899-3459
DOI	10.1097/RMR.0000000000000224
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Article ; Online: Accelerated brain aging in chronic low back pain.

Yu, Gary Z / Ly, Maria / Karim, Helmet T / Muppidi, Nishita / Aizenstein, Howard J / Ibinson, James W

Brain research

2021 Volume 1755, Page(s) 147263

Abstract: Chronic low back pain (CLBP) is a leading cause of disability and is associated with neurodegenerative changes in brain structure. These changes lead to impairments in cognitive function and are consistent with those seen in aging, suggesting an ... ...

Abstract	Chronic low back pain (CLBP) is a leading cause of disability and is associated with neurodegenerative changes in brain structure. These changes lead to impairments in cognitive function and are consistent with those seen in aging, suggesting an accelerated aging pattern. In this study we assessed this using machine-learning estimated brain age (BA) as a holistic metric of morphometric changes associated with aging. Structural imaging data from 31 non-depressed CLBP patients and 32 healthy controls from the Pain and Interoception Imaging Network were included. Using our previously developed algorithm, we estimated BA per individual based on grey matter density. We then conducted multivariable linear modeling for effects of group, chronological age, and their interaction on BA. We also performed two voxel-wise analyses comparing grey matter density between CLBP and control individuals and the association between gray matter density and BA. There was an interaction between CLBP and greater chronological age on BA such that the discrepancy in BA between healthy and CLBP individuals was greater for older individuals. In CLBP individuals, BA was not associated with sex, current level of pain, duration of CLBP, or mild to moderate depressive symptoms. CLBP individuals had lower cerebellar grey matter density compared to healthy individuals. Brain age was associated with lower gray matter density in numerous brain regions. CLBP was associated with greater BA, which was more profound in later life. BA as a holistic metric was sensitive to differences in gray matter density in numerous regions which eluded direct comparison between groups.
MeSH term(s)	Aging/physiology ; Cerebral Cortex/physiopathology ; Chronic Pain/physiopathology ; Cognition/physiology ; Gray Matter/physiopathology ; Humans ; Low Back Pain/physiopathology ; Magnetic Resonance Imaging/methods ; Pain Measurement
Language	English
Publishing date	2021-01-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2020.147263
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Article: A Homeostatic Model of Subjective Cognitive Decline.

Mizuno, Akiko / Ly, Maria / Aizenstein, Howard J

Brain sciences

2018 Volume 8, Issue 12

Abstract: Subjective Cognitive Decline (SCD) is possibly one of the earliest detectable signs of dementia, but we do not know which mental processes lead to elevated concern. In this narrative review, we will summarize the previous literature on the biomarkers and ...

Abstract	Subjective Cognitive Decline (SCD) is possibly one of the earliest detectable signs of dementia, but we do not know which mental processes lead to elevated concern. In this narrative review, we will summarize the previous literature on the biomarkers and functional neuroanatomy of SCD. In order to extend upon the prevailing theory of SCD, compensatory hyperactivation, we will introduce a new model: the breakdown of homeostasis in the prediction error minimization system. A cognitive prediction error is a discrepancy between an implicit cognitive prediction and the corresponding outcome. Experiencing frequent prediction errors may be a primary source of elevated subjective concern. Our homeostasis breakdown model provides an explanation for the progression from both normal cognition to SCD and from SCD to advanced dementia stages.
Language	English
Publishing date	2018-12-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci8120228
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Article: Soluble epoxide hydrolase inhibitor can protect the femoral head against tobacco smoke exposure-induced osteonecrosis in spontaneously hypertensive rats

Xu, Jingyi / Qiu, Xing / Yu, Gary / Ly, Maria / Yang, Jun / Silva, Rona M / Zhang, Xun / Yu, Mang / Wang, Yinong / Hammock, Bruce / Pinkerton, Kent E. / Zhao, Dewei

Toxicology. 2022 Jan. 15, v. 465

2022

Abstract: Exposure to tobacco smoke (TS) has been considered a risk factor for osteonecrosis of the femoral head (ONFH). Soluble epoxide hydrolase inhibitors (sEHIs) have been found to reduce inflammation and oxidative stress in a variety of pathologies. This ... ...

Abstract	Exposure to tobacco smoke (TS) has been considered a risk factor for osteonecrosis of the femoral head (ONFH). Soluble epoxide hydrolase inhibitors (sEHIs) have been found to reduce inflammation and oxidative stress in a variety of pathologies. This study was designed to assess the effect of sEHI on the development of ONFH phenotypes induced by TS exposure in spontaneously hypertensive (SH) rats. SH and normotensive Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or TS (80 mg/m3 particulate concentration) 6 h/day, 3 days/week for 8 weeks. During this period, sEHI was delivered through drinking water at a concentration of 6 mg/L. Histology, immunohistochemistry, and micro-CT morphometry were performed for phenotypic evaluation. As results, TS exposure induced significant increases in adipocyte area, bone specific surface (BS/BV), and trabecular separation (Tb.SP), as well as significant decreases in bone mineral density (BMD), percent trabecular area (Tb.Ar), HIF-1a expression, bone volume fraction (BV/TV), trabecular numbers (Tb.N), and trabecular thickness (Tb.Th) in both SH and WKY rats. However, the protective effects of sEHI were mainly observed in TS-exposed SH rats, specifically in the density of osteocytes, BMD, Tb.Ar, HIF-1a expression, BV/TV, BS/BV, Tb.N, and Tb.SP. Our study confirms that TS exposure can induce ONFH especially in SH rats, and suggests that sEHI therapy may protect against TS exposure-induced osteonecrotic changes in the femoral head.
Keywords	adipocytes ; air ; bone density ; epoxide hydrolase ; femur ; immunohistochemistry ; inflammation ; micro-computed tomography ; morphometry ; osteonecrosis ; oxidative stress ; phenotype ; risk factors ; smoke ; therapeutics ; tobacco ; toxicology
Language	English
Dates of publication	2022-0115
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2021.153045
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mesoscale diffusion magnetic resonance imaging of the ex vivo human hippocampus.

Ly, Maria / Foley, Lesley / Manivannan, Ashwinee / Hitchens, T Kevin / Richardson, R Mark / Modo, Michel

Human brain mapping

2020 Volume 41, Issue 15, Page(s) 4200–4218

Abstract: Mesoscale diffusion magnetic resonance imaging (MRI) endeavors to bridge the gap between macroscopic white matter tractography and microscopic studies investigating the cytoarchitecture of human brain tissue. To ensure a robust measurement of diffusion ... ...

Abstract	Mesoscale diffusion magnetic resonance imaging (MRI) endeavors to bridge the gap between macroscopic white matter tractography and microscopic studies investigating the cytoarchitecture of human brain tissue. To ensure a robust measurement of diffusion at the mesoscale, acquisition parameters were arrayed to investigate their effects on scalar indices (mean, radial, axial diffusivity, and fractional anisotropy) and streamlines (i.e., graphical representation of axonal tracts) in hippocampal layers. A mesoscale resolution afforded segementation of the pyramidal cell layer (CA1-4), the dentate gyrus, as well as stratum moleculare, radiatum, and oriens. Using ex vivo samples, surgically excised from patients with intractable epilepsy (n = 3), we found that shorter diffusion times (23.7 ms) with a b-value of 4,000 s/mm
MeSH term(s)	Aged ; Anterior Temporal Lobectomy ; Dentate Gyrus/diagnostic imaging ; Dentate Gyrus/pathology ; Diffusion Magnetic Resonance Imaging/methods ; Diffusion Magnetic Resonance Imaging/standards ; Diffusion Tensor Imaging/methods ; Diffusion Tensor Imaging/standards ; Epilepsy, Temporal Lobe/pathology ; Epilepsy, Temporal Lobe/surgery ; Female ; Gray Matter/diagnostic imaging ; Gray Matter/pathology ; Hippocampus/diagnostic imaging ; Hippocampus/pathology ; Humans ; Male ; Middle Aged ; Nerve Net/diagnostic imaging ; Nerve Net/pathology ; Perforant Pathway/diagnostic imaging ; Perforant Pathway/pathology ; Pyramidal Cells/cytology ; Pyramidal Cells/pathology
Language	English
Publishing date	2020-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1197207-5
ISSN	1097-0193 ; 1065-9471
ISSN (online)	1097-0193
ISSN	1065-9471
DOI	10.1002/hbm.25119
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Article: Low thalamic activity during a digit-symbol substitution task is associated with symptoms of subjective cognitive decline.

Mizuno, Akiko / Karim, Helmet Talib / Ly, Maria J / Lopresti, Brian J / Cohen, Ann D / Ali, Areej A / Mathis, Chester A / Klunk, William E / Aizenstein, Howard J / Snitz, Beth E

Frontiers in psychiatry

2023 Volume 14, Page(s) 1242822

Abstract: Introduction: Subjective cognitive decline (SCD) may represent the earliest preclinical stage of Alzheimer's Disease (AD) for some older adults. However, the underlying neurobiology of SCD is not completely understood. Since executive function may be ... ...

Abstract	Introduction: Subjective cognitive decline (SCD) may represent the earliest preclinical stage of Alzheimer's Disease (AD) for some older adults. However, the underlying neurobiology of SCD is not completely understood. Since executive function may be affected earlier than memory function in the progression of AD, we aimed to characterize SCD symptoms in terms of fMRI brain activity during the computerized digit-symbol substitution task (DSST), an executive function task. We also explored associations of DSST task performance with brain activation, SCD severity, and amyloid-ß (Aß) load. Methods: We analyzed data from 63 cognitively normal older individuals (mean age 73.6 ± 7.2) with varying degree of SCD symptoms. Participants completed a computerized version of DSST in the MR scanner and a Pittsburgh Compound-B (PiB)-PET scan to measure global cerebral Aß load. Results: A voxel-wise analysis revealed that greater SCD severity was associated with lower dorsomedial thalamus activation. While task performance was not associated with brain activation nor Aß load, slower reaction time was associated with greater SCD severity. Discussion: The observed lower dorsomedial thalamus activation may reflect declining familiarity-based working memory and the trans-thalamic executive function pathway in SCD. SCD symptoms may reflect altered neural function and subtle decline of executive function, while Aß load may have an indirect impact on neural function and performance. Self-perceived cognitive decline may serve as a psychological/subjective marker reflecting subtle brain changes.
Language	English
Publishing date	2023-09-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2023.1242822
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Article: Alzheimer Disease Pathology and Neurodegeneration in Midlife Obesity: A Pilot Study.

Dolatshahi, Mahsa / Commean, Paul K / Rahmani, Farzaneh / Liu, Jingxia / Lloyd, LaKisha / Nguyen, Caitlyn / Hantler, Nancy / Ly, Maria / Yu, Gary / Ippolito, Joseph E / Sirlin, Claude / Morris, John C / Benzinger, Tammie L S / Raji, Cyrus A

Aging and disease

2023

Abstract: Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of ... ...

Abstract	Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625789-0
ISSN	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2023.0707
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