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Item Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns(Wiley, 2024) Crane, Paul K.; Groot, Colin; Ossenkoppele, Rik; Mukherjee, Shubhabrata; Choi, Seo-Eun; Lee, Michael; Scollard, Phoebe; Gibbons, Laura E.; Sanders, R. Elizabeth; Trittschuh, Emily; Saykin, Andrew J.; Mez, Jesse; Nakano, Connie; Mac Donald, Christine; Sohi, Harkirat; Alzheimer’s Disease Neuroimaging Initiative; Risacher, Shannon; Medicine, School of MedicineIntroduction: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. Methods: We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. Results: There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10-10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. Discussion: MRI findings differ across cognitively defined AD subgroups.Item The human preference for symmetric walking often disappears when one leg is constrained(The Physiological Society, 2021) Browne, Michael G.; Smock, Cameron S.; Roemmich, Ryan T.; Medicine, School of MedicineWe hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained We studied healthy young adults and independently constrained one or both step lengths to be markedly shorter or longer than preferred using visual feedback When one leg was constrained to take a shorter or longer step than preferred, asymmetric walking patterns were less metabolically costly than symmetric walking patterns When one leg was constrained to take a shorter or longer step than preferred and the other leg was allowed to move freely, most participants naturally adopted an asymmetric gait People may prefer to walk asymmetrically to minimize metabolic power when the function of one leg is constrained during fixed-speed treadmill walking ABSTRACT: The bilateral symmetry inherent in healthy human walking is often disrupted in clinical conditions that primarily affect one leg (e.g. stroke). This seems intuitive: with one leg constrained, gait becomes asymmetric. However, the emergence of asymmetry is not inevitable. Consider that symmetric walking could be preserved by matching the movement of the unconstrained leg to that of the constrained leg. While this is theoretically possible, it is rarely observed in clinical populations. Here, we hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained, even when symmetric walking remains possible. We tested this hypothesis by performing two experiments in healthy adults. In Experiment 1, we constrained one step to be markedly shorter or longer than preferred. We observed that participants could significantly reduce metabolic power by adopting an asymmetric gait (one short/long step, one preferred step) rather than maintaining a symmetric gait (bilateral short/long steps). Indeed, when allowed to walk freely in this situation, participants naturally adopted a less effortful asymmetric gait. In Experiment 2, we applied a milder constraint that more closely approximated magnitudes of step length asymmetry that are observed in clinical populations. Responses in this experiment were more heterogeneous, though most participants adopted an asymmetric gait. These findings support two central conclusions: (1) symmetry is not necessarily energetically optimal in constrained human walking, and (2) people may prefer to walk asymmetrically to minimize metabolic power when one leg is constrained during fixed-speed treadmill walking, especially when the constraint is large.Item Intraeye retinal nerve fiber layer and macular thickness asymmetry measurements for the discrimination of primary open-angle glaucoma and normal tension glaucoma(Elsevier, 2016-04) Khanal, Safal; Davey, Pinakin Gunvant; Racette, Lyne; Thapa, Madhu; Department of Ophthalmology, IU School of MedicinePURPOSE: The aim of this study was to evaluate the diagnostic capability of intraeye retinal nerve fiber layer (RNFL) thickness and macular thickness (MT) asymmetry measurements for the discrimination of normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT). METHODS: A total of 90 subjects were enrolled including 30 consecutive healthy subjects, 30 consecutive subjects with POAG, and 30 consecutive subjects with NTG. RNFL thicknesses around the optic disc as well as MT measurements were taken with circular and radial SD-OCT scans. Intraeye retinal and MT asymmetry were calculated as the absolute difference between superior and inferior hemispheres of the eye using posterior pole asymmetry analysis protocol. Analysis of variance was used for comparison and areas under the receiver operating characteristic (AROC) were obtained for different parameters among the three diagnostic groups. RESULTS: There was a significant difference in MT asymmetry for all comparison groups (normal-NTG, p<0.05; normal-POAG, p<0.001; and NTG-POAG, p<0.001). Intraeye retinal nerve fiber thickness asymmetry measurements were not different between the groups (normal-NTG, p<0.187; normal-POAG, p<0.056; and NTG-POAG, p<0.837). The area under ROC curves exceeded 0.800 for all the studied parameters, including the MT asymmetry except for intraeye RNFL thickness asymmetry which had the lowest AROC as well as the least sensitivity for identifying subjects with NTG from normal (AROC=0.626, sensitivity=30%); POAG from normal (AROC=0.644, sensitivity=37%) and NTG from POAG (AROC=0.533, sensitivity=13%). CONCLUSION: The intraeye MT asymmetry holds significant potential as a distinguishing parameter for NTG and POAG.Item A Longitudinal Imaging Genetics Study of Neuroanatomical Asymmetry in Alzheimer's Disease(Elsevier, 2018-10-01) Wachinger, Christian; Nho, Kwangsik; Saykin, Andrew J.; Reuter, Martin; Rieckmann, Anna; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineNeuroanatomical asymmetries have recently been associated with the progression of Alzheimer’s disease (AD) but the biological basis of asymmetric brain changes in disease remains unknown. Methods We investigated genetic influences on brain asymmetry by identifying associations between MRI-derived measures of asymmetry and candidate single-nucleotide polymorphisms (SNPs) that have previously been identified in genome-wide association studies (GWAS) for AD diagnosis and for brain subcortical volumes. For the longitudinal neuroimaging data (1,241 individuals; 6,395 scans), we use a mixed effects model with interaction between genotype and diagnosis. Results We found significant associations between asymmetry of amygdala, hippocampus, and putamen and SNPs in the genes BIN1, CD2AP, ZCWPW1, ABCA7, TNKS, and DLG2. For AD candidate SNPs, we demonstrated an asymmetric effect on subcortical brain structures. Conclusions The associations between SNPs in the genes TNKS and DLG2 and AD-related increases in shape asymmetry are of particular interest; these SNPs have previously been associated with subcortical volumes of amygdala and putamen but have not yet been associated with Alzheimer’s pathology. This provides novel evidence about the biological underpinnings of brain asymmetry as a disease marker. Contralateral brain structures represent a unique, within-patient, reference element for disease and asymmetries can provide a personalized measure of the accumulation of past disease processes.