Kevin C Cain

University of Washington Seattle, Seattle, Washington, United States

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Publications (163)785.32 Total impact

  • No preview · Article · Nov 2015
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    ABSTRACT: Background/aims: To determine if potential biomarkers can be used to identify subgroups of people with irritable bowel syndrome (IBS) who will benefit the most or the least from a comprehensive self-management (CSM) intervention. Methods: In a two-armed randomized controlled trial a CSM (n = 46) was compared to a usual care (n = 46) group with follow-up at 3 and 6 months post randomization. Biomarkers obtained at baseline included heart rate variability, salivary cortisol, serum interleukin-10, and lactulose/mannitol ratio. Linear mixed models were used to test whether these biomarkers predicted improvements in the primary outcomes including daily abdominal pain, gastrointestinal Symptom Score and IBS-specific quality of life (QOL). Results: The nurse-delivered 8-session CSM intervention is more effective than usal care in reducing abdominal pain, Gastrointestinal symptom score and enhancing QOL. Participants with higher nighttime low frequency heart rate variability (vagal modulation) and increased low frequency/high frequency ratio (sympathovagal balance) had less benefit from CSM on abdominal pain. Salivary cortisol, IL-10, and lactulose/mannitol ratio were not statistically significant in predicting CSM benefit. Baseline symptom severity interacts with treatment, namely the benefit of CSM is greater in those with higher baseline symptoms. Conclusions: Cognitively-focused therapies may be less effective in reducing abdominal pain in IBS patients with higher sympathetic tone. Whether this a centrally-mediated patient characteristic or related to heightened arousal remains to be determined.
    No preview · Article · Oct 2015 · Journal of neurogastroenterology and motility
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    ABSTRACT: Qualitative monitoring of neuromuscular blockade using the train-of-four (TOF) count is widely used to determine the timing and dose of reversal agents for neuromuscular blockade. We compared TOF count measured manually by anesthesia providers with that determined by TOF-Watch(®) SX. This prospective observational cohort study included patients who were American Society of Anesthesiologists physical status III or less and undergoing elective surgery. During recovery from an intubating dose of rocuronium or vecuronium, the TOF count was measured every 15 sec using TOF-Watch SX. Anesthesia providers assessed the TOF count twice at each level of TOF-count, 15 sec after the TOF-Watch SX count increased to the next level and then two to five minutes later. In 75 patients, 687 observations were collected. There was agreement between the TOF-Watch SX and the subjective assessment by the provider in 386 (56%) of these observations. The agreement was 87% at TOF counts of 0 and 4. In the 409 observations at TOF counts 1, 2, and 3, the agreement was 36%. Among the 264 observations with disagreement at these TOF counts, providers assessed a higher TOF count in 254 (96%) observations and a lower count in 10 (4%) observations compared with the TOF-Watch SX. Anesthesia providers report higher values of TOF count compared with the TOF-Watch SX, especially at intermediate levels of neuromuscular blockade. Since the dosing guidelines for the timing and dose of reversal agents are based on the TOF count derived from the TOF-Watch SX, a manually assessed TOF count may lead to inadequate dosing and/or premature administration of reversal agents.
    No preview · Article · Jul 2015 · Canadian Anaesthetists? Society Journal

  • No preview · Article · Apr 2015 · Gastroenterology
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    Full-text · Dataset · Mar 2015
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    ABSTRACT: Introduction¿-Synuclein (¿-syn) is a key protein in Parkinson¿s disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In this study, CSF and clinical data were contributed by >300 subjects from three cohorts (the longitudinal DATATOP cohort, a large cross-sectional cohort, and a cohort of LRRK2 mutation carriers).ResultsConsistent with our previous observation that CSF pS129 positively correlated with Unified Parkinson¿s Disease Rating Scale (UPDRS) scores, CSF pS129 in the DATATOP cohort increased over approximately two years of disease progression (mean change 5.60 pg/ml, p¿=¿0.050). Intriguingly, in the DATATOP cohort, pS129 negatively correlated with UPDRS scores at the baseline (R¿=¿¿0.244, p¿=¿0.017), but not final point, suggesting that this association may depend on disease stage. Reanalysis of our previous cohort with stratification by PD stage, and addition of a cohort of LRRK2 mutation carriers with very early/preclinical PD, supported the idea that the relationship between CSF pS129 and disease severity over a wider range of PD stages might be represented with a U-shaped curve, in which lower pS129 levels correlated with worse clinical condition at early stages, but better condition at later stages.Conclusion The observation of a negative-to-positive transition of correlation of pS129 to disease severity as PD progresses could have profound impact on how pS129 is used as a biomarker clinically as well as in modeling PD experimentally.
    Full-text · Article · Jan 2015
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    ABSTRACT: Background: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-β 1-42 peptide (Aβ42) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis. Objective: To validate the analytical and clinical performance of the MSD t-tau and Aβ42 kits and propose diagnostic cut-off values for the field. Methods: The analytical performance of the CSF t-tau and Aβ42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, Aβ42, and t-tau/Aβ42 in three clinically characterized cohorts. Results: Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/Aβ42 performed the best. Conclusions: Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and Aβ42 assays. Based on a large, multi-center, clinically-diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, Aβ42, and t-tau/Aβ42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories.
    No preview · Article · Jan 2015 · Journal of Alzheimer's disease: JAD
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    ABSTRACT: A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jan 2015 · Parkinsonism & Related Disorders
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    ABSTRACT: Poststroke fatigue (PSF) is common, but the biological basis of this fatigue is unknown. We explored the possibility that PSF is related to systemic inflammation by investigating polymorphisms in 2 genes that affect the immune response. In a substudy of a larger trial that evaluated the role of the immune response on stroke outcome, fatigue was assessed at 30, 90, 180, and 365 days after ischemic stroke using the Fatigue Assessment Scale. Subjects were genotyped for 3 single nucleotide polymorphisms, one in the interleukin-1 receptor antagonist gene (IL1RN; rs4251961, a T/C substitution) and two in the in toll-like receptor-4 (TLR4) gene (1063 A/G [Asp299Gly] rs4986790 and 1363 C/T [Thr399Ile] rs4986791). Of the 39 participants, 22 (56%) endorsed fatigue during the study. The degree of fatigue was remarkably constant over time and independent of stroke outcome. The C allele of the rs4251961 single nucleotide polymorphism (SNP) in IL1RN was associated with self-reported fatigue (P = .03), whereas the cosegregating polymorphisms in TLR4 were associated with lower levels of fatigue (P = .04). SNPs in 2 genes with opposing effects on inflammatory immune responses were significantly, but differentially, associated with PSF. These findings suggest a direct link between immune signaling dysregulation and PSF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2014 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
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    ABSTRACT: Study objectives: Patients with irritable bowel syndrome (IBS) often report sleep disturbances. Previously, we have shown that self-reported sleep difficulties predicted exacerbations of next-day IBS symptoms, mood disturbance, and fatigue. The purpose of this study was to explore whether objectively measured sleep using actigraphy, as well as self-report, predicts next-day symptoms in women with IBS and to explore whether or not symptoms also predict self-report and objective sleep. Methods: Women aged 18-45 years with IBS were community-recruited (n = 24, mean age = 32 ± 8 years). Participants completed sleep and IBS symptom diaries for one menstrual cycle and wore Actiwatch-64 actigraphs for 7 days at home. Statistical analyses used generalized estimating equation (GEE) models. Results: Poorer self-reported sleep quality significantly (p < 0.05) predicted higher next-day abdominal pain, anxiety, and fatigue, but was not significant for gastrointestinal (GI) symptoms or depressed mood. Actigraphic sleep efficiency (SEF) significantly predicted worsening next-day anxiety and fatigue, but not abdominal pain, GI symptoms, or depressed mood. On temporally reversed analyses, none of the symptoms significantly predicted subsequent sleep, except that GI symptoms significantly predicted higher actigraphic sleep efficiency. Conclusion: This small exploratory study supports previous findings that self-reported sleep disturbance predicted exacerbation of next-day symptoms in women with IBS and extends this relationship using an objective sleep measure. The study adds further evidence that sleep quality predicts subsequent IBS symptoms, but not the converse. The findings from this small study support the importance of additional longitudinal research to further understand the relationships between sleep and IBS.
    No preview · Article · Sep 2014 · Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine
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    ABSTRACT: Toll-like receptor-4 (TLR4) is important in neuroinflammation. Single nucleotide polymorphisms (SNPs) in TLR4, including 1063 A/G [Asp299Gly] and 1363 C/T [Thr399Ile], are associated with altered immune responses but their effect on acute ischemic stroke (AIS) outcome is unknown. We collected demographic, clinical, laboratory, radiologic, and genotype data on 113 AIS patients and performed multivariate analyses to assess associations between TLR4 SNP haplotype and either neurological outcome, infection, or inflammatory markers. In adjusted analyses, TLR4 SNPs were associated with worse outcome as well as increases in circulating leukocytes, C-reactive protein, and interleukin-1 receptor antagonist. In AIS, variations in TLR4 may influence neurological outcome (for video abstract, please see Supplemental digital content 1 file,
    No preview · Article · May 2014 · Neuroreport
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    ABSTRACT: Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS-diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025-.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea. © The Author(s) 2015.
    No preview · Article · May 2014 · Gastroenterology
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    ABSTRACT: ProblemKorean American (KA) parents need a culturally tailored parent training that helps them bridge the Korean and American cultures and divergent parenting practices.Methods The Korean Parent Training Program (KPTP) was pilot tested with 48 KA mothers of children between 3 and 8 years old using a partial group-randomized controlled experimental study design. Researchers gathered self-report survey and observation data.FindingsAnalyses, which used generalized estimating equations, indicated the intervention group mothers increased use of effective parenting practices and their children decreased behavioral problems and reported less acculturation conflict with their mothers.Conclusion The KPTP is a promising way to promote effective parenting and increase positive child mental health in KA families.
    No preview · Article · Apr 2014 · Journal of Child and Adolescent Psychiatric Nursing
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    ABSTRACT: Most patients with Parkinson's disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of −0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, −0.12 (P = 0.037); delayed recall, −0.05 (P = 0.002); New Dot Test, −0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation.
    No preview · Article · Apr 2014 · American Journal Of Pathology
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    ABSTRACT: Patients with irritable bowel syndrome (IBS) often report higher levels of psychological distress, specifically anxiety, and depression than non-IBS patients. The management of gastrointestinal symptoms and psychological distress is demonstrably amenable to cognitive-behavioral therapies in a significant number of patients with IBS. The present secondary analysis evaluates the impact of nurse-delivered self-management interventions on anxiety, depression, and urine catecholamine levels in adult IBS patients. Participants in the study were randomized to 2 intervention groups of either comprehensive self-management (CSM) intervention or usual care control. Daily diary ratings of gastrointestinal symptoms, anxiety, and depression were recorded every evening for 28 days during the baseline period and subsequently at 3, 6, and 12 months postrandomization. Catecholamine levels of epinephrine and norepinephrine were measured from 4 weekly 1st morning urine samples at baseline as well as at each follow-up time. The CSM group reported significantly lower levels of anxiety and depression at follow-up than the usual care group (p = .018 and .021, respectively). In contrast, urine catecholamine levels displayed no appreciable change. Thus, although nurse-delivered CSM interventions showed no impact on urinary catecholamine levels, daily psychological distress was measurably reduced.
    No preview · Article · Jan 2014 · Gastroenterology nursing: the official journal of the Society of Gastroenterology Nurses and Associates
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    ABSTRACT: Evidence suggests that patients with irritable bowel syndrome (IBS) are more vigilant to pain-associated stimuli. The aims of this study were to compare women with IBS (n = 20) to healthy control (HC, n = 20) women on pain sensitivity, conditioned pain modulation (CPM) efficiency, and salivary cortisol levels before and after the CPM test and to examine the relationship of CPM efficiency with gastrointestinal pain, somatic pain, psychological distress symptoms, and salivary cortisol levels in each group. Women, aged 20-42 years, gave consent, completed questionnaires, and kept a symptom diary for 2 weeks. CPM efficiency was tested with a heat test stimulus and cold water condition stimulus in a laboratory between 8 and 10 a.m. on a follicular phase day. Salivary cortisol samples were collected just before and after the experimental testing. Compared to the HC group, women with IBS reported more days with gastrointestinal and somatic pain/discomfort, psychological distress, fatigue, and feeling stressed. During the CPM baseline testing, women with IBS reported greater pain sensitivity compared to the HC group. There was no significant group difference in salivary cortisol levels nor in CPM efficiency, though a post-hoc analysis showed a higher prevalence of impaired CPM efficiency among IBS subjects with more severe lower-GI symptoms. In the IBS group, reduced CPM efficiency was associated with daily abdominal pain/discomfort and psychological distress. Overall, women with IBS exhibited an increased sensitivity to thermal stimuli. Impaired CPM was present in a subset of women with IBS.
    No preview · Article · Jan 2014 · Biological Research for Nursing
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    ABSTRACT: Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10) levels, IBS life interference, and GI and psychological distress symptoms. In 88 women and 18 men with IBS, GI permeability was quantitated as percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10 was measured in supernatants from 72-h incubated, unstimulated PBMCs. Participants completed a 4-week daily diary recording IBS life interference on daily activities and work, IBS symptoms, and psychological distress symptoms. They also completed the Brief Symptom Inventory. The L/M ratio but not percent sucrose recovery was significantly correlated with IBS interference with activities and work and retrospectively measured anxiety and depression. Unstimulated PBMC production of IL-10 correlated significantly with IBS interference with daily work, IBS symptom score, and abdominal pain. We identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio who had substantially higher IBS interference and IBS symptom scores. Our findings suggest a distinct subgroup of IBS patients with alterations in gut barrier function. This subgroup is characterized by increased GI permeability and/or increased PBMC production of IL-10. These physiologic alterations reflect more severe IBS as measured by interference of IBS with daily activities and daily IBS symptoms.
    No preview · Article · Jan 2014 · Journal of Gastroenterology
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    ABSTRACT: Peroxiredoxins are endogenous antioxidants that function as peroxide and peroxynitrite scavengers. Extracellular peroxiredoxins, however, are shown to initiate inflammation within the ischemic brain through activation of Toll-like receptors. Based on this observation, we hypothesized that plasma peroxiredoxin concentrations in ischemic stroke would correlate biomarkers of inflammation and predict poor outcome. In a prospective study of patients with ischemic stroke, plasma peroxiredoxin 5 (PRX5) concentrations and inflammatory biomarkers at day 3 after stroke onset were correlated and the association between PRX5 at day 3 and outcome at 3 months assessed. PRX5 concentrations were available for 98 patients and were lower in those with more severe strokes (P=0.001). PRX5 was inversely correlated to biomarkers of inflammation at day 3 after stroke and did not predict 3-month outcome. Plasma PRX5 is decreased in severe stoke and inversely correlated to biomarkers of systemic inflammation. These data suggest that PRX5 is not a proinflammatory mediator in acute stroke. Moreover, the inverse relationship between PRX5 and stroke severity suggests that PRX5 is either consumed or its production is impaired in severe stroke. Further study is needed to define the potential role of PRX5 in stroke.
    No preview · Article · Jan 2014 · Stroke
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    ABSTRACT: Infection is a common phenomenon following stroke, and adversely affects outcome. Previous studies suggest that interleukin-1 receptor antagonist (IL-1ra) and single nucleotide polymorphisms (SNPs) in the IL1RN gene might influence the risk of post-stroke infection and outcome. In this study, we addressed the effects of the rs4251961 SNP in IL1RN on infection risk and outcome. Subjects with acute ischemic stroke were enrolled within 72 h of symptom onset and followed up to 1 year. Plasma IL-1ra was measured at multiple time points and outcome assessed at 1, 3, 6, and 12 months. Active surveillance for infection occurred while subjects were hospitalized. Subjects were genotyped for the IL1RN rs4251961 polymorphism. In the population of 113 subjects for this study, those with the minor C allele of rs4251961 polymorphism in IL1RN were more likely to be Caucasian, hypertensive, and to be afflicted with coronary heart disease. Higher plasma IL-1ra was associated with an increased risk of infection (other than pneumonia), and the minor C allele of rs4251961 was independently associated with a decreased risk of infection (other than pneumonia). Initial plasma IL-1ra was not predictive of long-term outcome, but patients with the minor C allele of rs4251961 were more likely to experience good (modified Rankin Score <2) long-term outcome. These data indicate that IL-1ra and IL1RN may influence the risk of infection after stroke, but this influence seems limited to infections other than pneumonia. Further studies are needed to better understand the complexities of immune regulation on infection and outcome after stroke.
    No preview · Article · Nov 2013 · Neurocritical Care
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    ABSTRACT: Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1–42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total tau or total tau/amyloid beta levels and the change of the Unified Parkinson Disease Rating Scale was observed. Notably, these correlations did not appear to be influenced by APOE genotype. These results are one of the very first pieces of evidence suggesting that tau and amyloid beta are critically involved in early Parkinson disease progression, potentially by a different mechanism than that in Alzheimer disease, although their applications as Parkinson disease progression markers will likely require the addition of other proteins.
    No preview · Article · May 2013 · Acta Neuropathologica

Publication Stats

5k Citations
785.32 Total Impact Points


  • 1988-2015
    • University of Washington Seattle
      • • Department of Biostatistics
      • • Department of Family and Child Nursing
      • • Department of Biobehavioral Nursing and Health Systems
      • • Department of Psychiatry and Behavioral Sciences
      • • School of Nursing
      • • Department of Psychosocial & Community Health
      • • Department of Family Medicine
      • • Department of Health Services
      • • Division of Gerontology and Geriatric Medicine
      • • Department of Medicine
      Seattle, Washington, United States
  • 1990
    • Swedish Medical Center Seattle
      Seattle, Washington, United States