Browsing by Author "Deardorff, Rachael"
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Item Advanced Meditation Alters Resting-State Brain Network Connectivity Correlating With Improved Mindfulness(Frontiers Media, 2021-11) Vishnubhotla, Ramana V.; Radhakrishnan, Rupa; Kveraga, Kestas; Deardorff, Rachael; Ram, Chithra; Pawale, Dhanashri; Wu, Yu-Chien; Renschler, Janelle; Subramaniam, Balachundhar; Sadhasivam, Senthilkumar; Radiology and Imaging Sciences, School of MedicinePurpose: The purpose of this study was to investigate the effect of an intensive 8-day Samyama meditation program on the brain functional connectivity using resting-state functional MRI (rs-fMRI). Methods: Thirteen Samyama program participants (meditators) and 4 controls underwent fMRI brain scans before and after the 8-day residential meditation program. Subjects underwent fMRI with a blood oxygen level dependent (BOLD) contrast at rest and during focused breathing. Changes in network connectivity before and after Samyama program were evaluated. In addition, validated psychological metrics were correlated with changes in functional connectivity. Results: Meditators showed significantly increased network connectivity between the salience network (SN) and default mode network (DMN) after the Samyama program (p < 0.01). Increased connectivity within the SN correlated with an improvement in self-reported mindfulness scores (p < 0.01). Conclusion: Samyama, an intensive silent meditation program, favorably increased the resting-state functional connectivity between the salience and default mode networks. During focused breath watching, meditators had lower intra-network connectivity in specific networks. Furthermore, increased intra-network connectivity correlated with improved self-reported mindfulness after Samyama.Item Amyloid and Tau Pathology are Associated with Cerebral Blood Flow in a Mixed Sample of Nondemented Older Adults with and without Vascular Risk Factors for Alzheimer’s Disease(Elsevier, 2023) Swinford, Cecily G.; Risacher, Shannon L.; Vosmeier, Aaron; Deardorff, Rachael; Chumin, Evgeny J.; Dzemidzic, Mario; Wu, Yu-Chien; Gao, Sujuan; McDonald, Brenna C.; Yoder, Karmen K.; Unverzagt, Frederick W.; Wang, Sophia; Farlow, Martin R.; Brosch, Jared R.; Clark, David G.; Apostolova, Liana G.; Sims, Justin; Wang, Danny J.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineIdentification of biomarkers for the early stages of Alzheimer's disease (AD) is an imperative step in developing effective treatments. Cerebral blood flow (CBF) is a potential early biomarker for AD; generally, older adults with AD have decreased CBF compared to normally aging peers. CBF deviates as the disease process and symptoms progress. However, further characterization of the relationships between CBF and AD risk factors and pathologies is still needed. We assessed the relationships between CBF quantified by arterial spin-labeled magnetic resonance imaging, hypertension, APOEε4, and tau and amyloid positron emission tomography in 77 older adults: cognitively normal, subjective cognitive decline, and mild cognitive impairment. Tau and amyloid aggregation were related to altered CBF, and some of these relationships were dependent on hypertension or APOEε4 status. Our findings suggest a complex relationship between risk factors, AD pathologies, and CBF that warrants future studies of CBF as a potential early biomarker for AD.Item Association between BrainAGE and Alzheimer's disease biomarkers(Wiley, 2025-02-27) Abughofah, Yousaf; Deardorff, Rachael; Vosmeier, Aaron; Hottle, Savannah; Dage, Jeffrey L.; Dempsey, Desarae; Apostolova, Liana G.; Brosch, Jared; Clark, David; Farlow, Martin; Foroud, Tatiana; Gao, Sujuan; Wang, Sophia; Zetterberg, Henrik; Blennow, Kaj; Saykin, Andrew J.; Risacher, Shannon L.; Radiology and Imaging Sciences, School of MedicineIntroduction: The brain age gap estimation (BrainAGE) method uses a machine learning model to generate an age estimate from structural magnetic resonance imaging (MRI) scans. The goal was to study the association of brain age with Alzheimer's disease (AD) imaging and plasma biomarkers. Methods: One hundred twenty-three individuals from the Indiana Memory and Aging Study underwent structural MRI, amyloid and tau positron emission tomography (PET), and plasma sampling. The MRI scans were processed using the software program BrainAgeR to receive a "brain age" estimate. Plasma biomarker concentrations were measured, and partial Pearson correlation models were used to evaluate their relationship with brain age gap (BAG) estimation (BrainAGE = chronological age - MRI estimated brain age). Results: Significant associations between BAG and amyloid and tau levels on PET and in plasma were observed depending on diagnostic categories. Discussion: These findings suggest that BAG is potentially a biomarker of pathology in AD which can be applied to routine brain imaging. Highlights: Novel research that uses an artificial intelligence learning tool to estimate brain age. Findings suggest that brain age gap is associated with plasma and positron emission tomography Alzheimer's disease (AD) biomarkers. Differential relationships are seen in different stages of disease (preclinical vs. clinical). Results could play a role in early AD diagnosis and treatment.Item Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer’s Disease(IOS Press, 2023) Mathew, Sunu; WuDunn, Darrell; Mackay, Devin D.; Vosmeier, Aaron; Tallman, Eileen F.; Deardorff, Rachael; Harris, Alon; Farlow, Martin R.; Brosch, Jared R.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Risacher, Shannon L.; Radiology and Imaging Sciences, School of MedicineBackground: The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina. Objective: To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. Methods: 75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. Results: Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes. Conclusion: RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.Item BrainAGE Estimation: Influence of Field Strength, Voxel Size, Race, and Ethnicity(medRxiv, 2023-12-05) Dempsey, Desarae A.; Deardorff, Rachael; Wu, Yu-Chien; Yu, Meichen; Apostolova, Liana G.; Brosch, Jared; Clark, David G.; Farlow, Martin R.; Gao, Sujuan; Wang, Sophia; Saykin, Andrew J.; Risacher, Shannon L.; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineThe BrainAGE method is used to estimate biological brain age using structural neuroimaging. However, the stability of the model across different scan parameters and races/ethnicities has not been thoroughly investigated. Estimated brain age was compared within- and across- MRI field strength and across voxel sizes. Estimated brain age gap (BAG) was compared across demographically matched groups of different self-reported races and ethnicities in ADNI and IMAS cohorts. Longitudinal ComBat was used to correct for potential scanner effects. The brain age method was stable within field strength, but less stable across different field strengths. The method was stable across voxel sizes. There was a significant difference in BAG between races, but not ethnicities. Correction procedures are suggested to eliminate variation across scanner field strength while maintaining accurate brain age estimation. Further studies are warranted to determine the factors contributing to racial differences in BAG.Item Comparison of multi-shot and single shot echo-planar diffusion tensor techniques for the optic pathway in patients with neurofibromatosis type 1(Springer, 2019-04) Ho, Chang Y.; Deardorff, Rachael; Kralik, Stephen F.; West, John D.; Wu, Yu-Chien; Shih, Chie-Schin; Radiology and Imaging Sciences, School of MedicinePurpose Diffusion tensor imaging (DTI) may be helpful in assessing optic pathway integrity as a marker for treatment in neurofibromatosis type 1 (NF1) patients with optic gliomas (OG). However, susceptibility artifacts are common in typical single-shot echo planar imaging (ssDTI). A readout-segmented multi-shot EPI technique (rsDTI) was utilized to minimize susceptibility distortions of the skull base and improve quantitative metrics. Methods Healthy controls, children with NF1 without OG, and NF1 with OG ± visual symptoms were included. All subjects were scanned with both rsDTI and ssDTI sequences sequentially. Diffusion metrics and deterministic fiber tracking were calculated. Tract count, volume, and length were also compared by a two-factor mixed ANOVA. Results Five healthy controls, 7 NF1 children without OG, and 12 NF1 children with OG were imaged. Six OG patients had visual symptoms. Four subjects had no detectable optic pathway fibers on ssDTI due to susceptibility, for which rsDTI was able to delineate. Tract count (p < 0.001), tract volume (p < 0.001), and FA (P < 0.001) were significantly higher for rsDTI versus ssDTI for all subjects. MD (p < 0.001) and RD (p < 0.001) were significantly lower for rsDTI vs ssDTI. Finally, MD, AD, and RD had a significantly lower difference in NF1 children with visual symptoms compared to NF1 children without visual symptoms only on ssDTI scans. Conclusion DTI with readout-segmented multi-shot EPI technique can better visualize the optic pathway and allow more confident measurements of anisotropy in NF1 patients. This is shown by a significant increase in FA, tract count, and volume with rsDTI versus ssDTI.Item CYP1B1-RMDN2 Alzheimer's disease endophenotype locus identified for cerebral tau PET(Springer Nature, 2024-09-20) Nho, Kwangsik; Risacher, Shannon L.; Apostolova, Liana G.; Bice, Paula J.; Brosch, Jared R.; Deardorff, Rachael; Faber, Kelley; Farlow, Martin R.; Foroud, Tatiana; Gao, Sujuan; Rosewood, Thea; Kim, Jun Pyo; Nudelman, Kelly; Yu, Meichen; Aisen, Paul; Sperling, Reisa; Hooli, Basavaraj; Shcherbinin, Sergey; Svaldi, Diana; Jack, Clifford R., Jr.; Jagust, William J.; Landau, Susan; Vasanthakumar, Aparna; Waring, Jeffrey F.; Doré, Vincent; Laws, Simon M.; Masters, Colin L.; Porter, Tenielle; Rowe, Christopher C.; Villemagne, Victor L.; Dumitrescu, Logan; Hohman, Timothy J.; Libby, Julia B.; Mormino, Elizabeth; Buckley, Rachel F.; Johnson, Keith; Yang, Hyun-Sik; Petersen, Ronald C.; Ramanan, Vijay K.; Ertekin-Taner, Nilüfer; Vemuri, Prashanthi; Cohen, Ann D.; Fan, Kang-Hsien; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Ali, Muhammad; Benzinger, Tammie; Cruchaga, Carlos; Hobbs, Diana; De Jager, Philip L.; Fujita, Masashi; Jadhav, Vaishnavi; Lamb, Bruce T.; Tsai, Andy P.; Castanho, Isabel; Mill, Jonathan; Weiner, Michael W.; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Department of Defense Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI); Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Study (A4 Study) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN); Australian Imaging, Biomarker & Lifestyle Study (AIBL); Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineDetermining the genetic architecture of Alzheimer's disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. rs2113389 is associated with higher CYP1B1 expression and methylation levels. Mouse model studies provide additional functional evidence for a relationship between CYP1B1 and tau deposition but not amyloid beta. These results provide insight into the genetic basis of cerebral tau deposition and support novel pathways for therapeutic development in AD.Item Head injury is associated with tau deposition on PET in MCI and AD patients(Wiley, 2021-08-24) Risacher, Shannon L.; West, John D.; Deardorff, Rachael; Gao, Sujuan; Farlow, Martin R.; Brosch, Jared R.; Apostolova, Liana G.; McAllister, Thomas W.; Wu, Yu-Chien; Jagust, William J.; Landau, Susan M.; Weiner, Michael W.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineIntroduction: Head injuries (HI) are a risk factor for dementia, but the underlying etiology is not fully known. Understanding whether tau might mediate this relationship is important. Methods: Cognition and tau deposition were compared between 752 individuals with (impaired, n = 302) or without cognitive impairment (CN, n = 450) with amyloid and [18F]flortaucipir positron emission tomography, HI history information, and cognitive testing from the Alzheimer's Disease Neuroimaging Initiative and the Indiana Memory and Aging Study. Results: Sixty-three (38 CN, 25 impaired) reported a history of HI. Higher neuropsychiatric scores and poorer memory were observed in those with a history of HI. Tau was higher in individuals with a history of HI, especially those who experienced a loss of consciousness (LOC). Results were driven by impaired individuals, especially amyloid beta-positive individuals with history of HI with LOC. Discussion: These findings suggest biological changes, such as greater tau, are associated with HI in individuals with cognitive impairment. Small effect sizes were observed; thus, further studies should replicate and extend these results.Item Relationship of retinal vasculature with measures of amyloid, tau, and neurodegeneration across the AD continuum(Wiley, 2025-01-09) Mathew, Sunu; Mackay, Devin; Tallman, Eileen F.; Deardorff, Rachael; Hottle, Savannah; Vosmeier, Aaron; Clark, David G.; Farlow, Martin R.; Brosch, Jared R.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Risacher, Shannon L.; Neurology, School of MedicineBackground: The eye often reflects changes seen in the brain in neurodegenerative diseases. This study sought to examine the relationship of retinal vasculature measured using optical coherence tomography angiography (OCTA) with temporal lobe neurodegeneration, and cerebral amyloid and tau deposition, in older adults along the Alzheimer’s disease (AD) continuum. Method: Participants included 13 cognitively normal subjects, 5 with subjective cognitive decline (SCD), 7 with cognitive impairment (mild cognitive impairment [MCI] and AD) from the Indiana Memory and Aging Study at the Indiana ADRC. Participants were excluded from the study if they had significant eye disease determined to interfere with OCTA, non‐AD dementia, or exclusion for MRI or PET. OCTA scans were obtained from each eye to measure retinal vessel density and perfusion density. MRI scans were processed using Freesurfer v6 to measure medial (MTL) and lateral temporal lobe (LTL) volumes. LTL SUVR values were extracted from [18F]flortaucipir PET scans. Finally, the association between retinal perfusion and vessel density with hippocampal volume, MTL tau, and lateral parietal amyloid was assessed using a partial Pearson correlation, covaried for age, sex, and diagnosis. p<0.05 was considered significant. Result: Retinal vessel and perfusion density were decreased in patients with AD. The right and left hippocampal volume were significantly correlated with retinal vessel density and perfusion density in the right eye and left hippocampal volume was correlated with vessel density in the left eye, but it did not reach significance. The retinal vessel density and perfusion density in the right eye correlated significantly with lateral parietal lobe amyloid and medial temporal lobe tau. Finally, the total gray matter volume correlated significantly with the retinal vessel density and perfusion density in the right eye and inversely with the foveal avascular zone in the right eye. Conclusion: Retinal perfusion and vessel density correlates with hippocampal atrophy, and general atrophy of the gray matter. It is also significantly correlated with the deposition of amyloid and tau in the brain. Imaging the retinal vasculature may represent a useful biomarker to screen patients at risk for AD prior to more invasive and prolonged testing.Item Spatial transcriptomic patterns underlying amyloid-β and tau pathology are associated with cognitive dysfunction in Alzheimer’s disease(Elsevier, 2024) Yu, Meichen; Risacher, Shannon L.; Nho, Kwangsik T.; Wen, Qiuting; Oblak, Adrian L.; Unverzagt, Frederick W.; Apostolova, Liana G.; Farlow, Martin R.; Brosch, Jared R.; Clark, David G.; Wang, Sophia; Deardorff, Rachael; Wu, Yu-Chien; Gao, Sujuan; Sporns, Olaf; Saykin, Andrew J.; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Radiology and Imaging Sciences, School of MedicineAmyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts. We identify AD susceptibility genes and gene modules in a gene co-expression network with expression profiles specifically related to regional vulnerability to Aβ and tau pathologies in AD. In addition, we identify distinct biochemical pathways associated with the gene-to-Aβ and the gene-to-tau associations. These findings may explain the discordance between regional Aβ and tau pathologies. Finally, we propose an analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations.