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OBJECTIVE To characterize pulse oxygen saturation (SpO2) trajectories and respiratory interventions after birth for newborns with cyanotic congenital heart disease (CCHD). STUDY DESIGN Retrospective single-site study of newborns ≥32 weeks gestation with CCHD: single ventricle with critical aortic obstruction (SV-CAO), critical pulmonic obstruction (CPO), transposition of the great arteries (TGA). Minute-to-minute SpO2 values and respiratory interventions were summarized and compared. RESULTS Two hundred infants were enrolled. SpO2 at each minute differed across groups (p

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

Aim To assess visual attention of neonatal team leaders during delivery room resuscitation of preterm infants using eye tracking glasses. Methods Prospective observational eye tracking study. Gaze fixations and sequences were captured, categorized, and mapped during the first 5 min of the resuscitations. Gaze fixation metrics of total gaze duration, visit count, and visit duration were summarized and compared based on interventions performed and provider training level. Fixation sequences were compared between attending neonatologists and fellows. Results During 18 eye tracking recordings, practitioners focused most of their cumulative visual attention on the infant (median total gaze duration 57%, interquartile range [IQR] 38–61%), followed by monitors (24%, IQR 13–46%), clinical staff (5%, IQR 1–8%), other physical objects (4%, IQR 3–6%), T-piece resuscitator (2%, IQR 0–4%) and the Apgar timer (1%, IQR 0–2%). Visual attention parameters varied according to intervention, with higher visit counts on the infant during corrective ventilation steps than during Continuous Positive Airway Pressure (CPAP) or Positive Pressure Ventilation (PPV), and longer visit durations on monitors during PPV. Time and frequency-based measures of visual attention did not significantly differ by provider training level, but patterned fixation sequences were identified among attending neonatologists that were not observed in fellows. Conclusion Team leaders predominantly gazed upon the infant and monitors during resuscitation, and visual attention parameters varied depending on the respiratory interventions performed. Attending neonatologists exhibited patterned fixation sequences that were not observed in fellows. Study results may have implications for optimizing delivery room design and training novice providers.

OBJECTIVES To characterize neonatal-perinatal medicine fellows’ progression toward neonatal intubation procedural competence during fellowship training. METHODS Multi-center cohort study of neonatal intubation encounters performed by neonatal-perinatal medicine fellows between 2014 through 2018 at North American academic centers in the National Emergency Airway Registry for Neonates. Cumulative sum analysis was used to characterize progression of individual fellows’ intubation competence, defined by an 80% overall success rate within 2 intubation attempts. We employed multivariable analysis to assess the independent impact of advancing quarter of fellowship training on intubation success. RESULTS There were 2297 intubation encounters performed by 92 fellows in 8 hospitals. Of these, 1766 (77%) were successful within 2 attempts. Of the 40 fellows assessed from the start of training, 18 (45%) achieved procedural competence, and 12 (30%) exceeded the deficiency threshold. Among fellows who achieved competence, the number of intubations to meet this threshold was variable, with an absolute range of 8 to 46 procedures. After adjusting for patient and practice characteristics, advancing quarter of training was independently associated with an increased odds of successful intubation (adjusted odds ratio: 1.10; 95% confidence interval 1.07–1.14). CONCLUSIONS The number of neonatal intubations required to achieve procedural competence is variable, and overall intubation competence rates are modest. Although repetition leads to skill acquisition for many trainees, some learners may require adjunctive educational strategies. An individualized approach to assess trainees’ progression toward intubation competence is warranted.

BackgroundA respiratory function monitor (RFM) provides real-time positive pressure ventilation feedback. Whether providers use RFM during neonatal resuscitation is unknown.MethodsAncillary study to the MONITOR(NCT03256578) randomised controlled trial. Neonatal resuscitation leaders at two centres wore eye-tracking glasses, and visual attention (VA) patterns were compared between RFM-visible and RFM-masked groups.Results14 resuscitations (6 RFM-visible, 8 RFM-masked) were analysed. The median total gaze duration on the RFM was significantly higher with a visible RFM (29% vs 1%, pConclusionProviders’ VA patterns differed during neonatal resuscitation when the RFM was visible, emphasising the importance of studying the impact of additional delivery room technology on providers’ behaviour.

Objective Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. Method 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. Results Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. Conclusions This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

Childhood adversity, such as physical, sexual, and verbal abuse, as well as neglect and family conflict, is a risk factor for schizophrenia. Such adversity can lead to disruptions of cognitive function during development, undermining intellectual capabilities and academic achievement. Schizophrenia is a neurodevelopmental disorder that is associated with cognitive impairments that may become evident during childhood. The Australian Schizophrenia Research Bank database comprises a large community cohort (N = 1169) in which we previously identified 3 distinct cognitive groups among people with schizophrenia: (1) Compromised, current, and estimated premorbid cognitive impairment; (2) Deteriorated, substantial decline from estimated premorbid function; and (3) Preserved, performing in the normal cognitive range without decline. The compromised group displayed the worst functional and symptom outcomes. Here, we extend our previous work by assessing the relationship among these categories of cognitive abilities and reported childhood adversity in 836 patients and healthy controls. Exploratory factor analysis of the Childhood Adversity Questionnaire revealed 3 factors (lack of parental involvement; overt abuse; family breakdown and hardship). People with schizophrenia reported significantly more childhood adversity than healthy controls on all items and factors. People with schizophrenia in the compromised group reported significantly more lack of parental involvement and family breakdown and hardship and lower socioeconomic status than those in the deteriorated group. The cognitive groups were not related to family history of psychosis. These findings identify specific social and family factors that impact cognition, highlighting the important role of these factors in the development of cognitive and functional abilities in schizophrenia.

BACKGROUND: Schizophrenia is characterized by positive and negative symptoms and cognitive deficits related to functional disability. Approved treatments targeting small molecule neurotransmitter receptors are limited in their effectiveness and often leave residual symptoms and debilitating side effects. Psychotic symptoms, cognitive deficits, and treatment response are variable in schizophrenia, highlighting heterogeneity in the etiology and presentation of the illness. There is a critical need for novel treatments targeting subgroups related to underlying biology that can be identified by biomarkers. A substantial subgroup (40%) of people with schizophrenia can be distinguished by cytokines in both peripheral blood and in brain. The cytokine interleukin 1-beta (IL-1β) mRNA and protein levels are significantly increased in serum, plasma, white blood cells, cerebrospinal fluid and brain in chronically ill patients and in first episode psychosis. Canakinumab is an approved human anti-IL-1β monoclonal antibody that interferes with the bioactivity of IL-1β and interrupts excessive immune response. However, the extent to which IL-1β blockade by canakinumab can reduce peripheral markers of an overactive immune system (e.g., high sensitivity C-reactive protein: hsCRP) and reduce psychotic symptom severity in schizophrenia is unknown. METHODS: We conducted a randomized, placebo-controlled, double-blind, parallel group trial of the monoclonal antibody canakinumab to block IL-1β in schizophrenia. Twenty-seven chronically ill patients with schizophrenia or schizoaffective disorder who had elevated peripheral inflammation markers (IL-1β, IL-6, hsCRP and/or neutrophil to lymphocyte ratio) at baseline were randomized to a one-time subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive treatment to antipsychotics. Peripheral hsCRP levels were measured at baseline (prior to injection) and at 1, 4- and 8-weeks post treatment. Positive and Negative Syndrome Scale scores were assessed at baseline and at 4- and 8-weeks post treatment. RESULTS: Separate t-tests comparing canakinumab or placebo at weeks 1, 4, and 8 to baseline showed significant reductions in peripheral hsCRP levels at all time points (all p’s < .02) for canakinumab only. Separate t-tests also showed a significant reduction in positive symptom severity scores at week 8 (p = 0.05) for canakinumab and at week 4 (p = 0.02) for placebo. There was a trend for low peripheral hsCRP levels to be strongly correlated with low positive symptom severity scores (r = .57, p = .07) only at week 8 in the canakinumab group. There were no significant reductions in negative or general psychopathology symptom severity scores in either group. DISCUSSION: Blockade of the cytokine IL-1β by the monoclonal antibody canakinumab significantly reduces peripheral hsCRP serum levels and these reductions may be related to a reduction in positive symptom severity in chronically ill patients with schizophrenia. Importantly, only those patients who initially displayed elevated peripheral markers of inflammation were recruited. The effects of canakinumab on the reduction of peripheral hsCRP is potentially beneficial to general health. The relatively strong relationship between the effects of canakinumab on the biological marker hsCRP and positive symptom severity after 8 weeks of treatment supports the effect of canakinumab on positive symptom severity. Given that treatment with a monoclonal antibody is a novel and substantial advance in the potential treatment of psychotic symptom severity in schizophrenia, future studies should consider increased or top-up doses with longer follow-up to confirm the benefit of adjunctive canakinumab treatment in schizophrenia.

ObjectiveTo assess the accuracy of real-time delivery room resuscitation documentation.DesignRetrospective observational study.SettingLevel 3 academic neonatal intensive care unit.ParticipantsFifty infants with video recording of neonatal resuscitation.Main outcome measuresVital sign assessments and interventions performed during resuscitation. The accuracy of written documentation was compared with video gold standard.ResultsTiming of initial heart rate assessment agreed with video in 44/50 (88%) records; the documented heart rate was correct in 34/44 (77%) of these. Heart rate and oxygen saturation were documented at 5 min of life in 90% of resuscitations. Of these, 100% of heart rate and 93% of oxygen saturation values were correctly recorded. Written records accurately reflected the mode(s) of respiratory support for 89%–100%, procedures for 91%–100% and medications for 100% of events.ConclusionReal-time documentation correctly reflects interventions performed during delivery room resuscitation but is less accurate for early vital sign assessments.

The rs1076560 polymorphism of DRD2 (encoding dopamine receptor D2) is associated with alternative splicing and cognitive functioning; however, a mechanistic relationship to schizophrenia has not been shown. Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture. Collectively, this work implicates rs1076560(T) as one possible risk factor for schizophrenia in the Han Chinese population, and suggests molecular mechanisms by which it may exert such influence.

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

ObjectiveA respiratory function monitor (RFM) may improve positive pressure ventilation (PPV) technique, but many providers do not use RFM data appropriately during delivery room resuscitation. We sought to use eye-tracking technology to identify RFM parameters that neonatal providers view most commonly during simulated PPV.DesignMixed methods study. Neonatal providers performed RFM-guided PPV on a neonatal manikin while wearing eye-tracking glasses to quantify visual attention on displayed RFM parameters (ie, exhaled tidal volume, flow, leak). Participants subsequently provided qualitative feedback on the eye-tracking glasses.SettingLevel 3 academic neonatal intensive care unit.ParticipantsTwenty neonatal resuscitation providers.Main outcome measuresVisual attention: overall gaze sample percentage; total gaze duration, visit count and average visit duration for each displayed RFM parameter. Qualitative feedback: willingness to wear eye-tracking glasses during clinical resuscitation.ResultsTwenty providers participated in this study. The mean gaze sample captured wa s 93% (SD 4%). Exhaled tidal volume waveform was the RFM parameter with the highest total gaze duration (median 23%, IQR 13–51%), highest visit count (median 5.17 per 10 s, IQR 2.82–6.16) and longest visit duration (median 0.48 s, IQR 0.38–0.81 s). All participants were willing to wear the glasses during clinical resuscitation.ConclusionWearable eye-tracking technology is feasible to identify gaze fixation on the RFM display and is well accepted by providers. Neonatal providers look at exhaled tidal volume more than any other RFM parameter. Future applications of eye-tracking technology include use during clinical resuscitation.

Plasma sphingolipids have been shown to predict cognitive impairment and hippocampal volume loss, but there is little research in patients with Alzheimer's disease (AD). In this study we sought to determine whether plasma ceramides, dihydroceramides (DHCer), sphingomyelins (SM), or dihydrosphingomyelin (DHSM) levels and ratios of SM/ceramide or DHSM/DHCer were predictive of progression in AD. Probable AD patients (n = 120) were enrolled in the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine. Plasma sphingolipids were assessed using ESI/MS/MS. Linear mixed effects models were used to examine the relation between baseline plasma sphingolipid levels and cross-sectional and longitudinal performance on the Mini-Mental State Exam (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating-Sum of Boxes (CDR-Sum). Participants were followed a mean of 4.2 visits and 2.3 years. There were no cross-sectional associations. In longitudinal analyses, high levels of DHCer and ceramide were associated with greater progression, but findings did not reach significance (p > 0.05). In contrast, higher plasma levels of SM, DHSM, SM/ceramide, and DHSM/DHCer ratios were associated with less progression on the MMSE and ADAS-Cog; the ratios were the strongest predictors of clinical progression. Compared to the lowest tertiles, the highest tertiles of DHSM/DHCer and SM/ceramide ratios declined 1.35 points (p = 0.001) and 1.19 (p = 0.004) points less per year on the MMSE and increased 3.18 (p = 0.001) and 2.42 (p = 0.016) points less per year on the ADAS-Cog. These results suggest that increased SM/ceramide and DHSM/DHCer ratios dose-dependently predict slower progression among AD patients and may be sensitive blood-based biomarkers for clinical progression.

Cognitive heterogeneity among people with schizophrenia has been defined on the basis of premorbid and current intelligence quotient (IQ) estimates. In a relatively large, community cohort, we aimed to independently replicate and extend cognitive subtyping work by determining the extent of symptom severity and functional deficits in each group. A total of 635 healthy controls and 534 patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited through the Australian Schizophrenia Research Bank. Patients were classified into cognitive subgroups on the basis of the Wechsler Test of Adult Reading (a premorbid IQ estimate) and current overall cognitive abilities into preserved, deteriorated, and compromised groups using both clinical and empirical (k-means clustering) methods. Additional cognitive, functional, and symptom outcomes were compared among the resulting groups. A total of 157 patients (29%) classified as ‘preserved’ performed within one s.d. of control means in all cognitive domains. Patients classified as ‘deteriorated’ (n=239, 44%) performed more than one s.d. below control means in all cognitive domains except estimated premorbid IQ and current visuospatial abilities. A separate 138 patients (26%), classified as ‘compromised,’ performed more than one s.d. below control means in all cognitive domains and displayed greater impairment than other groups on symptom and functional measures. In the present study, we independently replicated our previous cognitive classifications of people with schizophrenia. In addition, we extended previous work by demonstrating worse functional outcomes and symptom severity in the compromised group. Patients with schizophrenia can be categorized into distinct groups according to their cognitive functioning abilities, say scientists. Cognitive impairment and intellect changes following the onset of schizophrenia are well documented, but recent research suggests that patients are affected in many different ways. Thomas Weickert at the University of New South Wales, Sydney, and co-workers across Australia conducted a large-scale study involving 635 healthy controls and 534 patients with schizophrenic symptoms to verify the presence of three distinct cognitive phenotypes in schizophrenia. Utilizing a test to determine pre-illness intelligence, the team classified patients into three categories: 29% were deemed to have 'preserved' relatively high levels of cognitive function, 44% had 'deteriorated' cognition, and 26% displayed 'compromised' cognitive abilities prior to illness onset which persisted and were related to disability. Such classification could help doctors provide tailored treatments and inform understanding of disease progression.

A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=-0.40, P=0.002) between serum VEGF and total frontal pole volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia.

Patients with the semantic variant of primary progressive aphasia, also known as semantic dementia, and Alzheimer's disease have deficits in semantic memory. However, few comparative studies have been performed to determine whether these patient groups have distinct semantic memory impairments. We asked 15 patients with semantic variant primary progressive aphasia and 57 patients with Alzheimer's disease to judge semantic category membership of coloured photos and printed words that are members of familiar natural and manufactured categories, and we related performance to grey matter atrophy. We found that both semantic variant primary progressive aphasia and Alzheimer's disease are significantly impaired on this task. Moreover, patients with semantic variant primary progressive aphasia had a significantly more prominent deficit for natural objects than their own deficit judging manufactured objects. Both semantic variant primary progressive aphasia and Alzheimer's disease had atrophy that included portions of the left temporal lobe. Regression analyses related performance in semantic variant primary progressive aphasia to ventral and medial portions of the left temporal lobe, while regression analyses in Alzheimer's disease related performance to these ventral and medial temporal areas as well as lateral temporal-parietal regions in the left hemisphere. We conclude that both semantic variant primary progressive aphasia and Alzheimer's disease are significantly impaired in a simple category membership judgement task and the selective impairment for natural kinds in semantic variant primary progressive aphasia is related in part to disease in visual association cortex in ventral-medial portions of the left temporal lobe. We discuss factors that may contribute to the semantic memory deficit in semantic variant primary progressive aphasia.

Objective: A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA. Methods: We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality. We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits. Results: We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant. Conclusions: These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics.

Plasma sphingolipids have been shown to predict cognitive impairment and hippocampal volume loss, but there is little research in patients with Alzheimer’s disease dementia (AD). In this study we sought to determine whether plasma ceramides, dihydroceramides (DHCer), sphingomyelins (SM), or dihydrosphingomyelin (DHSM) levels and ratios of SM/ceramide or DHSM/DHCer were predictive of progression in AD. Probable AD patients (n=120) were enrolled in the Alzheimer’s Disease and Memory Disorders Center at Baylor College of Medicine. Plasma sphingolipids were assessed using ESI/MS/MS. Linear mixed effects models were used to examine the relation between baseline plasma sphingolipid levels and cross-sectional and longitudinal performance on the Mini-Mental State Exam (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating-Sum of Boxes (CDR-Sum). Participants were followed a mean of 4.2 visits and 2.3 years. There were no crosssectional associations. In longitudinal analyses, high levels of DHCer and ceramide were associated with greater progression, but findings did not reach significance (p>0.05). In contrast, higher plasma levels of SM, DHSM, SM/ceramide and DHSM/DHCer ratios were associated with less progression on the MMSE and ADAS-Cog; the ratios were the strongest predictors of clinical progression. Compared to the lowest tertiles, the highest tertiles of DHSM/DHCer and SM/ ceramide ratios declined 1.35 points (p=0.001) and 1.19 (p=0.004) less per year on the MMSE and increased 3.18 points (p=0.001) and 2.42 (p=0.016) less per year on the ADAS-Cog. These results suggest that increased SM/ceramide and DHSM/DHCer ratios dose-dependently predict slower progression among AD patients and may be sensitive blood-based biomarkers for clinical progression.