Browsing by Author "Lad, Eleonora M"

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    Accelerated Brain Atrophy, Microstructural Decline and Connectopathy in Age-Related Macular Degeneration.
    (Biomedicines, 2024-01-10) Stout, Jacques A; Mahzarnia, Ali; Dai, Rui; Anderson, Robert J; Cousins, Scott; Zhuang, Jie; Lad, Eleonora M; Whitaker, Diane B; Madden, David J; Potter, Guy G; Whitson, Heather E; Badea, Alexandra
    Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and dynamics of AMD-related brain changes. Voxel-based analyses at the first visit identified reduced volume in AMD participants in the cuneate gyrus, associated with vision, and the temporal and bilateral cingulate gyrus, linked to higher cognition and memory. The second visit occurred 2 years after the first and revealed that AMD participants had reduced cingulate and superior frontal gyrus volumes, as well as lower fractional anisotropy (FA) for the bilateral occipital lobe, including the visual and the superior frontal cortex. We detected faster rates of volume and FA reduction in AMD participants in the left temporal cortex. We identified inter-lingual and lingual-cerebellar connections as important differentiators in AMD participants. Bundle analyses revealed that the lingual gyrus had a lower streamline length in the AMD participants at the first visit, indicating a connection between retinal and brain health. FA differences in select inter-lingual and lingual cerebellar bundles at the second visit showed downstream effects of vision loss. Our analyses revealed widespread changes in AMD participants, beyond brain networks directly involved in vision processing.
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    Cerebral white matter connectivity, cognition, and age-related macular degeneration.
    (NeuroImage. Clinical, 2021-02-23) Zhuang, Jie; Madden, David J; Cunha, Priscila; Badea, Alexandra; Davis, Simon W; Potter, Guy G; Lad, Eleonora M; Cousins, Scott W; Chen, Nan-Kuei; Allen, Kala; Maciejewski, Abigail J; Fernandez, Xuan Duong; Diaz, Michele T; Whitson, Heather E
    Age-related macular degeneration (AMD) is a common retina disease associated with cognitive impairment in older adults. The mechanism(s) that account for the link between AMD and cognitive decline remain unclear. Here we aim to shed light on this issue by investigating whether relationships between cognition and white matter in the brain differ by AMD status. In a direct group comparison of brain connectometry maps from diffusion weighted images, AMD patients showed significantly weaker quantitative anisotropy (QA) than healthy controls, predominantly in the splenium and left optic radiation. The QA of these tracts, however, did not correlate with the visual acuity measure, indicating that this group effect is not directly driven by visual loss. The AMD and control groups did not differ significantly in cognitive performance.Across all participants, better cognitive performance (e.g. verbal fluency) is associated with stronger connectivity strength in white matter tracts including the splenium and the left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. However, there were significant interactions between group and cognitive performance (verbal fluency, memory), suggesting that the relation between QA and cognitive performance was weaker in AMD patients than in controls.This may be explained by unmeasured determinants of performance that are more common or impactful in AMD or by a recruitment bias whereby the AMD group had higher cognitive reserve. In general, our findings suggest that neural degeneration in the brain might occur in parallel to AMD in the eyes, although the participants studied here do not (yet) exhibit overt cognitive declines per standard assessments.
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    Perioperative Blindness in Spine Surgery: A Scoping Literature Review.
    (Journal of clinical medicine, 2024-02) Sperber, Jacob; Owolo, Edwin; Zachem, Tanner J; Bishop, Brandon; Johnson, Eli; Lad, Eleonora M; Goodwin, C Rory
    Perioperative vision loss (POVL) is a devastating surgical complication that impacts both the recovery from surgery and quality of life, most commonly occurring after spine surgery. With rates of spine surgery dramatically increasing, the prevalence of POVL will increase proportionately. This scoping review aims to aggregate the literature pertinent to POVL in spine surgery and consolidate recommendations and preventative measures to reduce the risk of POVL. There are several causes of POVL, and the main contribution following spine surgery is ischemic optic neuropathy (ION). Vision loss often manifests immediately following surgery and is irreversible and severe. Diffusion weighted imaging has recently surfaced as a diagnostic tool to identify ION. There are no effective treatments; therefore, risk stratification for counseling and prevention are vital. Patients undergoing prone surgery of long duration and/or with significant expected blood loss are at greatest risk. Future research is necessary to develop effective treatments.
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    Phonemic fluency and brain connectivity in age-related macular degeneration: a pilot study.
    (Brain connectivity, 2015-03) Whitson, Heather E; Chou, Ying-Hui; Potter, Guy G; Diaz, Michele T; Chen, Nan-Kuei; Lad, Eleonora M; Johnson, Micah A; Cousins, Scott W; Zhuang, Jie; Madden, David J
    Age-related macular degeneration (AMD), the leading cause of blindness in developed nations, has been associated with poor performance on tests of phonemic fluency. This pilot study sought to (1) characterize the relationship between phonemic fluency and resting-state functional brain connectivity in AMD patients and (2) determine whether regional connections associated with phonemic fluency in AMD patients were similarly linked to phonemic fluency in healthy participants. Behavior-based connectivity analysis was applied to resting-state, functional magnetic resonance imaging data from seven patients (mean age=79.9±7.5 years) with bilateral AMD who completed fluency tasks prior to imaging. Phonemic fluency was inversely related to the strength of functional connectivity (FC) among six pairs of brain regions, representing eight nodes: left opercular portion of inferior frontal gyrus (which includes Broca's area), left superior temporal gyrus (which includes part of Wernicke's area), inferior parietal lobe (bilaterally), right superior parietal lobe, right supramarginal gyrus, right supplementary motor area, and right precentral gyrus. The FC of these reference links was not related to phonemic fluency among 32 healthy individuals (16 younger adults, mean age=23.5±4.6 years and 16 older adults, mean age=68.3±3.4 years). Compared with healthy individuals, AMD patients exhibited higher mean connectivity within the reference links and within the default mode network, possibly reflecting compensatory changes to support performance in the setting of reduced vision. These findings are consistent with the hypothesis that phonemic fluency deficits in AMD reflect underlying brain changes that develop in the context of AMD.
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    Relating Sensory, Cognitive, and Neural Factors to Older Persons' Perceptions about Happiness: An Exploratory Study.
    (Journal of aging research, 2018-01) Horne, Alexandra J; Chiew, Kimberly S; Zhuang, Jie; George, Linda K; Adcock, R Alison; Potter, Guy G; Lad, Eleonora M; Cousins, Scott W; Lin, Frank R; Mamo, Sara K; Chen, Nan-Kuei; Maciejewski, Abigail J; Duong Fernandez, Xuan; Whitson, Heather E
    Despite increased rates of disease, disability, and social losses with aging, seniors consistently report higher levels of subjective well-being (SWB), a construct closely related to happiness, than younger adults. In this exploratory study, we utilized an available dataset to investigate how aspects of health commonly deteriorating with age, including sensory (i.e., vision and hearing) and cognitive status, relate to variability in self-described contributors to happiness. Community-dwelling seniors (n = 114) responded to a single-item prompt: "name things that make people happy." 1731 responses were categorized into 13 domains of SWB via structured content analysis. Sensory health and cognition were assessed by Snellen visual acuity, pure-tone audiometry, and in-person administration of the Brief Test of Adult Cognition by Telephone (BTACT) battery. A subset of eligible participants (n = 57) underwent functional magnetic resonance imaging (fMRI) to assess resting state functional connectivity (FC) within a previously described dopaminergic network associated with reward processing. SWB response patterns were relatively stable across gender, sensory status, and cognitive performance with few exceptions. For example, hearing-impaired participants listed fewer determinants of SWB (13.59 vs. 17.16; p < 0.001) and were less likely to name things in the "special events" category. Participants with a higher proportion of responses in the "accomplishments" domain (e.g., winning, getting good grades) demonstrated increased FC between the ventral tegmental area and nucleus accumbens, regions implicated in reward and motivated behavior. While the framework for determinants of happiness among seniors was largely stable across the factors assessed here, our findings suggest that subtle changes in this construct may be linked to sensory loss. The possibility that perceptions about determinants of happiness might relate to differences in intrinsic connectivity within reward-related brain networks also warrants further investigation.
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    Relationship between neural functional connectivity and memory performance in age-related macular degeneration.
    (Neurobiology of aging, 2020-11) Zuo, Xintong; Zhuang, Jie; Chen, Nan-Kuei; Cousins, Scott; Cunha, Priscila; Lad, Eleonora M; Madden, David J; Potter, Guy; Whitson, Heather E
    Age-related macular degeneration (AMD) has been linked to memory deficits, with no established neural mechanisms. We collected resting-state brain functional magnetic resonance imaging and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysis to quantify the strength of functional connectivity between hubs of the default mode network and a network of medial temporal regions relevant for memory. Our results indicated neither memory performance nor network connectivity differed by AMD status. However, the AMD participants exhibited stronger relationships than the controls between memory performance and connectivity from the memory network hub (left parahippocampal) to 2 other regions: the left temporal pole and the right superior/middle frontal gyri. Also, the connectivity between the medial prefrontal cortex and posterior cingulate cortex of default mode network correlated more strongly with memory performance in AMD compared to control. We concluded that stronger brain-behavior correlation in AMD may suggest a role for region-specific connectivity in supporting memory in the context of AMD.
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    The RUSH2A Study: Best-Corrected Visual Acuity, Full-Field Electroretinography Amplitudes, and Full-Field Stimulus Thresholds at Baseline.
    (Translational vision science & technology, 2020-10-08) Birch, David G; Cheng, Peiyao; Duncan, Jacque L; Ayala, Allison R; Maguire, Maureen G; Audo, Isabelle; Cheetham, Janet K; Durham, Todd A; Fahim, Abigail T; Ferris, Frederick L; Heon, Elise; Huckfeldt, Rachel M; Iannaccone, Alessandro; Khan, Naheed W; Lad, Eleonora M; Michaelides, Michel; Pennesi, Mark E; Stingl, Katarina; Vincent, Ajoy; Weng, Christina Y; Foundation Fighting Blindness Consortium Investigator Group

    Purpose

    The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), full-field stimulus thresholds (FST), and their relationship with baseline demographic and clinical characteristics in the Rate of Progression in Usher syndrome type 2 (USH2A)-related Retinal Degeneration (RUSH2A) multicenter study.

    Methods

    Participants had Usher syndrome type 2 (USH2, N = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, N = 47) associated with biallelic variants in the USH2A gene. Associations of demographic and clinical characteristics with BCVA, ERG, and FST were assessed with regression models.

    Results

    In comparison to ARRP, USH2 had worse BCVA (median 79 vs. 82 letters; P < 0.001 adjusted for age), lower rod-mediated ERG b-wave amplitudes (median 0.0 vs. 6.6 µV; P < 0.001) and 30 Hz flicker cone-mediated ERG amplitudes (median 1.5 vs. 3.1 µV; P = 0.001), and higher (white, blue, and red) FST thresholds (means [-26, -31, -23 dB] vs. [-39, -45, -28 dB]; P < 0.001 for all stimuli). After adjusting for age, gender, and duration of vision loss, the difference in BCVA between diagnosis groups was attenuated (P = 0.09). Only diagnosis was associated with rod- and cone-mediated ERG parameters, whereas both genders (P = 0.04) and duration of visual loss (P < 0.001) also were associated with FST white stimulus.

    Conclusions

    USH2 participants had worse BCVA, ERG, and FST than ARRP participants. FST was strongly associated with duration of disease; it remains to be determined whether it will be a sensitive measure of progression.

    Translational relevance

    Using standardized research protocols in RUSH2A, measures have been identified to monitor disease progression and treatment response and differentiate features of prognostic relevance between USH2 and ARRP participants with USH2A mutations.