Browsing by Author "Whitson, Heather E"
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Item Open Access A Systematic Review of Conceptual Frameworks of Medical Complexity and New Model Development.(J Gen Intern Med, 2016-03) Zullig, Leah L; Whitson, Heather E; Hastings, Susan N; Beadles, Chris; Kravchenko, Julia; Akushevich, Igor; Maciejewski, Matthew LBACKGROUND: Patient complexity is often operationalized by counting multiple chronic conditions (MCC) without considering contextual factors that can affect patient risk for adverse outcomes. OBJECTIVE: Our objective was to develop a conceptual model of complexity addressing gaps identified in a review of published conceptual models. DATA SOURCES: We searched for English-language MEDLINE papers published between 1 January 2004 and 16 January 2014. Two reviewers independently evaluated abstracts and all authors contributed to the development of the conceptual model in an iterative process. RESULTS: From 1606 identified abstracts, six conceptual models were selected. One additional model was identified through reference review. Each model had strengths, but several constructs were not fully considered: 1) contextual factors; 2) dynamics of complexity; 3) patients' preferences; 4) acute health shocks; and 5) resilience. Our Cycle of Complexity model illustrates relationships between acute shocks and medical events, healthcare access and utilization, workload and capacity, and patient preferences in the context of interpersonal, organizational, and community factors. CONCLUSIONS/IMPLICATIONS: This model may inform studies on the etiology of and changes in complexity, the relationship between complexity and patient outcomes, and intervention development to improve modifiable elements of complex patients.Item Open Access 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, AlexandraAge-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.Item Open Access 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 EAge-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.Item Open Access Comorbid visual and cognitive impairment: relationship with disability status and self-rated health among older Singaporeans.(Asia-Pacific journal of public health, 2014-05) Whitson, Heather E; Malhotra, Rahul; Chan, Angelique; Matchar, David B; Østbye, TrulsThe objective of this study was to examine the prevalence and consequences of coexisting vision and cognitive impairments in an Asian population. Data were collected from 4508 community-dwelling Singaporeans aged 60 years and older. Cognition was assessed by the Short Portable Mental Status Questionnaire whereas vision, disability, and self-rated health (SRH) were determined by self-report. Vision impairment was present in 902 (18.5%) participants and cognitive impairment in 835 (13.6%), with 232 (3.5%) participants experiencing both impairments. Persons with the comorbidity experienced higher odds of disability than persons with either single impairment. The association of vision impairment with SRH was stronger among women (odds ratio [OR] = 6.79, 95% confidence interval [CI] = 4.64-9.92) than among men (OR = 1.71, 95% CI = 1.21-2.41). Concurrent cognitive and vision impairment is prevalent in older Singaporeans and is associated with high rates of disability. Gender differences in vision-dependent roles may affect the patient-perceived impact of this comorbidity.Item Open Access Engineering Virtuous health habits using Emotion and Neurocognition: Flexibility for Lifestyle Optimization and Weight management (EVEN FLOW).(Frontiers in aging neuroscience, 2023-01) Smith, Patrick J; Whitson, Heather E; Merwin, Rhonda M; O'Hayer, C Virginia; Strauman, Timothy JInterventions to preserve functional independence in older adults are critically needed to optimize 'successful aging' among the large and increasing population of older adults in the United States. For most aging adults, the management of chronic diseases is the most common and impactful risk factor for loss of functional independence. Chronic disease management inherently involves the learning and adaptation of new behaviors, such as adopting or modifying physical activity habits and managing weight. Despite the importance of chronic disease management in older adults, vanishingly few individuals optimally manage their health behavior in the service of chronic disease stabilization to preserve functional independence. Contemporary conceptual models of chronic disease management and health habit theory suggest that this lack of optimal management may result from an underappreciated distinction within the health behavior literature: the behavioral domains critical for initiation of new behaviors (Initiation Phase) are largely distinct from those that facilitate their maintenance (Maintenance Phase). Psychological factors, particularly experiential acceptance and trait levels of openness are critical to engagement with new health behaviors, willingness to make difficult lifestyle changes, and the ability to tolerate aversive affective responses in the process. Cognitive factors, particularly executive function, are critical to learning new skills, using them effectively across different areas of life and contextual demands, and updating of skills to facilitate behavioral maintenance. Emerging data therefore suggests that individuals with greater executive function are better able to sustain behavior changes, which in turn protects against cognitive decline. In addition, social and structural supports of behavior change serve a critical buffering role across phases of behavior change. The present review attempts to address these gaps by proposing a novel biobehavioral intervention framework that incorporates both individual-level and social support system-level variables for the purpose of treatment tailoring. Our intervention framework triangulates on the central importance of self-regulatory functioning, proposing that both cognitive and psychological mechanisms ultimately influence an individuals' ability to engage in different aspects of self-management (individual level) in the service of maintaining independence. Importantly, the proposed linkages of cognitive and affective functioning align with emerging individual difference frameworks, suggesting that lower levels of cognitive and/or psychological flexibility represent an intermediate phenotype of risk. Individuals exhibiting self-regulatory lapses either due to the inability to regulate their emotional responses or due to the presence of executive functioning impairments are therefore the most likely to require assistance to preserve functional independence. In addition, these vulnerabilities will be more easily observable for individuals requiring greater complexity of self-management behavioral demands (e.g. complexity of medication regimen) and/or with lesser social support. Our proposed framework also intuits several distinct intervention pathways based on the profile of self-regulatory behaviors: we propose that individuals with intact affect regulation and impaired executive function will preferentially respond to 'top-down' training approaches (e.g., strategy and process work). Individuals with intact executive function and impaired affect regulation will respond to 'bottom-up' approaches (e.g., graded exposure). And individuals with impairments in both may require treatments targeting caregiving or structural supports, particularly in the context of elevated behavioral demands.Item Open Access Language processing in age-related macular degeneration associated with unique functional connectivity signatures in the right hemisphere.(Neurobiol Aging, 2017-11-14) Zhuang, Jie; Madden, David J; Duong-Fernandez, Xuan; Chen, Nan-Kuei; Cousins, Scott W; Potter, Guy G; Diaz, Michele T; Whitson, Heather EAge-related macular degeneration (AMD) is a retinal disease associated with significant vision loss among older adults. Previous large-scale behavioral studies indicate that people with AMD are at increased risk of cognitive deficits in language processing, particularly in verbal fluency tasks. The neural underpinnings of any relationship between AMD and higher cognitive functions, such as language processing, remain unclear. This study aims to address this issue using independent component analysis of spontaneous brain activity at rest. In 2 components associated with visual processing, we observed weaker functional connectivity in the primary visual cortex and lateral occipital cortex in AMD patients compared with healthy controls, indicating that AMD might lead to differences in the neural representation of vision. In a component related to language processing, we found that increasing connectivity within the right inferior frontal gyrus was associated with better verbal fluency performance across all older adults, and the verbal fluency effect was greater in AMD patients than controls in both right inferior frontal gyrus and right posterior temporal regions. As the behavioral performance of our patients is as good as that of controls, these findings suggest that preservation of verbal fluency performance in AMD patients might be achieved through higher contribution from right hemisphere regions in bilateral language networks. If that is the case, there may be an opportunity to promote cognitive resilience among seniors with AMD or other forms of late-life vision loss.Item Open Access Maintenance and Representation of Mind Wandering during Resting-State fMRI.(Scientific reports, 2017-01-12) Chou, Ying-Hui; Sundman, Mark; Whitson, Heather E; Gaur, Pooja; Chu, Mei-Lan; Weingarten, Carol P; Madden, David J; Wang, Lihong; Kirste, Imke; Joliot, Marc; Diaz, Michele T; Li, Yi-Ju; Song, Allen W; Chen, Nan-KueiMajor advances in resting-state functional magnetic resonance imaging (fMRI) techniques in the last two decades have provided a tool to better understand the functional organization of the brain both in health and illness. Despite such developments, characterizing regulation and cerebral representation of mind wandering, which occurs unavoidably during resting-state fMRI scans and may induce variability of the acquired data, remains a work in progress. Here, we demonstrate that a decrease or decoupling in functional connectivity involving the caudate nucleus, insula, medial prefrontal cortex and other domain-specific regions was associated with more sustained mind wandering in particular thought domains during resting-state fMRI. Importantly, our findings suggest that temporal and between-subject variations in functional connectivity of above-mentioned regions might be linked with the continuity of mind wandering. Our study not only provides a preliminary framework for characterizing the maintenance and cerebral representation of different types of mind wandering, but also highlights the importance of taking mind wandering into consideration when studying brain organization with resting-state fMRI in the future.Item Open Access Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study(British Journal of Anaesthesia, 2021-09) Browndyke, Jeffrey N; Wright, Mary C; Yang, Rosa; Syed, Ayesha; Park, John; Hall, Ashley; Martucci, Katherine; Devinney, Michael J; Shaw, Leslie; Waligorska, Teresa; Moretti, Eugene W; Whitson, Heather E; Cohen, Harvey J; Mathew, Joseph P; Berger, Miles; MADCO-PC InvestigatorsItem Open Access 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 JAge-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.Item Open Access Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers.(Annals of clinical and translational neurology, 2022-02) Berger, Miles; Browndyke, Jeffrey N; Cooter Wright, Mary; Nobuhara, Chloe; Reese, Melody; Acker, Leah; Bullock, W Michael; Colin, Brian J; Devinney, Michael J; Moretti, Eugene W; Moul, Judd W; Ohlendorf, Brian; Laskowitz, Daniel T; Waligorska, Teresa; Shaw, Leslie M; Whitson, Heather E; Cohen, Harvey J; Mathew, Joseph P; MADCO-PC InvestigatorsObjective
Numerous investigators have theorized that postoperative changes in Alzheimer's disease neuropathology may underlie postoperative neurocognitive disorders. Thus, we determined the relationship between postoperative changes in cognition and cerebrospinal (CSF) tau, p-tau-181p, or Aβ levels after non-cardiac, non-neurologic surgery in older adults.Methods
Participants underwent cognitive testing before and 6 weeks after surgery, and lumbar punctures before, 24 h after, and 6 weeks after surgery. Cognitive scores were combined via factor analysis into an overall cognitive index. In total, 110 patients returned for 6-week postoperative testing and were included in the analysis.Results
There was no significant change from before to 24 h or 6 weeks following surgery in CSF tau (median [median absolute deviation] change before to 24 h: 0.00 [4.36] pg/mL, p = 0.853; change before to 6 weeks: -1.21 [3.98] pg/mL, p = 0.827). There were also no significant changes in CSF p-tau-181p or Aβ over this period. There was no change in cognitive index (mean [95% CI] 0.040 [-0.018, 0.098], p = 0.175) from before to 6 weeks after surgery, although there were postoperative declines in verbal memory (-0.346 [-0.523, -0.170], p = 0.003) and improvements in executive function (0.394, [0.310, 0.479], p < 0.001). There were no significant correlations between preoperative to 6-week postoperative changes in cognition and CSF tau, p-tau-181p, or Aβ42 changes over this interval (p > 0.05 for each).Interpretation
Neurocognitive changes after non-cardiac, non-neurologic surgery in the majority of cognitively healthy, community-dwelling older adults are unlikely to be related to postoperative changes in AD neuropathology (as assessed by CSF Aβ, tau or p-tau-181p levels or the p-tau-181p/Aβ or tau/Aβ ratios).Trial registration
clinicaltrials.gov (NCT01993836).Item Open Access 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 EDespite 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.Item Open Access 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 EAge-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.Item Open Access The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction.(Journal of the American Geriatrics Society, 2019-01-23) Berger, Miles; Oyeyemi, Deborah; Olurinde, Mobolaji O; Whitson, Heather E; Weinhold, Kent J; Woldorff, Marty G; Lipsitz, Lewis A; Moretti, Eugene; Giattino, Charles M; Roberts, Kenneth C; Zhou, Junhong; Bunning, Thomas; Ferrandino, Michael; Scheri, Randall P; Cooter, Mary; Chan, Cliburn; Cabeza, Roberto; Browndyke, Jeffrey N; Murdoch, David M; Devinney, Michael J; Shaw, Leslie M; Cohen, Harvey Jay; Mathew, Joseph P; INTUIT InvestigatorsBACKGROUND/OBJECTIVES:Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. DESIGN:Observational prospective cohort. SETTING:Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. PARTICIPANTS:Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. MEASUREMENTS:Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. CONCLUSION:INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae.Item Open Access Trajectories of functional ability over the life course: a conceptual model of the interaction of stressor-induced functional loss and resilience.(System dynamics review, 2018-10) Matchar, David B; Ansah, John P; Koh, Victoria; Whitson, Heather EUnderstanding the factors that influence functional ability over the life course is integral to identifying clinical and public health policies to facilitate successful aging. The World Health Organization has advocated a conceptual framework to clarify the policy discussion. We have sought to translate this general framework into an explicit system dynamics model of the interaction of physiological loss, stressors and endogenous responses to produce a familiar variety of trajectories of functional ability over the life courses. Simulation experiments were implemented for both a 30-month duration with only one major stressor; and for the life course with an initial major stressor and subsequent stressors determined by the level of functional ability. For both contexts, variations in the few parameters in the scenarios led to a realistic range of trajectories of function over time.Item Open Access Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.(Journal of Alzheimer's disease : JAD, 2022-12) Parker, Daniel C; Kraus, William E; Whitson, Heather E; Kraus, Virginia B; Smith, Patrick J; Cohen, Harvey Jay; Pieper, Carl F; Faldowski, Richard A; Hall, Katherine S; Huebner, Janet L; Ilkayeva, Olga R; Bain, James R; Newby, L Kristin; Huffman, Kim MBackground
The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD).Objective
The objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study.Methods
The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7).Results
Over two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (β= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (β= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (β= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aβ42/Aβ40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers.Conclusion
Our findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis.