Melody Reese

All Publications

• Biomarkers. Alzheimer's & dementia : the journal of the Alzheimer's Association Reese, M., Cooter, M., Roberts, K. C., Woldorff, M. G., Browndyke, J. N., Shaw, L. M., Waligorska, T., Zetterberg, H., Blennow, K., Berger, M. 2024; 20 Suppl 2: e089088

  Abstract

  Postoperative delirium (POD) is characterized by fluctuating attention after surgery and is associated with increased risk of developing Alzheimer's Disease (AD). While the neurophysiological changes that underlie POD and increased risk of AD are unclear, recent data has raised the possibility that an exaggerated brain response to anesthetics may be a biomarker for POD risk and preclinical AD-like pathology. Thus, we examined whether anesthetic-dose-adjusted intraoperative brain activity is associated with POD or preoperative brain vulnerabilities (preclinical AD-like pathology, preoperative inattention) that may contribute to risk of POD (and later AD).82 patients from 3 prospective cohort studies of non-cardiac, non-neurologic surgical patients age ≥60 who had sufficient 32-channel intraoperative electroencephalographic (EEG) data and received a gas anesthetic for ≥80% of their surgery were included. Other data included preoperative cerebrospinal fluid (CSF) samples, preoperative cognitive testing, and delirium scores (before surgery and twice daily for ≤5 days after surgery). Univariable associations were evaluated between 8-12Hz anesthetic-dose-adjusted frontoparietal EEG alpha power and 1) preoperative CSF AD biomarkers (pTau181p, Aβ42, pTau181p/Aβ42), 2) preoperative attention function, and 3) POD incidence and severity. To account for the brain's response to anesthetics, alpha power was dose-adjusted as follows: (alpha power at each minute of surgery) / (2.5 - age-adjusted minimum alveolar concentration at each minute of surgery) and summarized by patient across minutes as the mean of median-filtered alpha.Lower dose-adjusted intraoperative frontoparietal alpha power was found among patients 1) with (vs. without) preoperative pTau/Aβ pathology (Table 1), and 2) among those who scored worse on timed preoperative attention tasks (Table 2). Low dose-adjusted alpha power was also associated with increased odds of POD and moderate-to-severe delirium symptomology (Table 3). The conclusions were similar for unadjusted alpha power, though only dose-adjusted values were associated with POD severity. Overall, the results suggest that, regardless of our anesthetic-dose-adjustment, low intraoperative frontoparietal alpha power is associated with CSF pTau/Aβ pathology, attention function, and POD.Future studies are needed to determine whether there are causal pathways between preoperative brain vulnerabilities, intraoperative frontoparietal alpha power, and POD. Understanding these pathways will improve our ability to identify at-risk patients for targeted interventions.

  View details for DOI 10.1002/alz.089088

  View details for PubMedID 39784456

• Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome MOLECULAR AUTISM Norris, J. E., Berry-Kravis, E. M., Harnett, M. D., Reines, S. A., Reese, M. A., Outterson, A. H., Michalak, C., Furman, J., Gurney, M. E., Ethridge, L. E. 2024; 15 (1): 47

  Abstract

  Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS.

  View details for DOI 10.1186/s13229-024-00626-0

  View details for Web of Science ID 001346179600001

  View details for PubMedID 39488698

  View details for PubMedCentralID PMC11531107

• Corrigendum to "A real-time neurophysiologic stress test for the aging brain: Novel perioperative and ICU applications of EEG in older surgical patients" Neurotherapeutics 20 (4) (2023) 975-1000. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics Berger, M., Ryu, D., Reese, M., McGuigan, S., Evered, L. A., Price, C. C., Scott, D. A., Westover, M. B., Eckenhoff, R., Bonanni, L., Sweeney, A., Babiloni, C. 2024: e00473

  View details for DOI 10.1016/j.neurot.2024.e00473

  View details for PubMedID 39482181

• Prediction of Post-Operative Delirium in Older Adults from Preoperative Cognition and Alpha Power from Resting-State EEG. medRxiv : the preprint server for health sciences Ning, M., Rodionov, A., Ross, J. M., Ozdemir, R. A., Burch, M., Lian, S. J., Alsop, D., Cavallari, M., Dickerson, B. C., Fong, T. G., Jones, R. N., Libermann, T. A., Marcantonio, E. R., Santarnecchi, E., Schmitt, E. M., Touroutoglou, A., Travison, T. G., Acker, L., Reese, M., Sun, H., Westover, B., Berger, M., Pascual-Leone, A., Inouye, S. K., Shafi, M. M., SAGES II Study Group and the INTUIT/PRIME Study Groups 2024

  Abstract

  Postoperative Delirium (POD) is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. The development of new tools to identify individuals at high risk for POD could guide clinical decision-making and enable targeted interventions to potentially decrease delirium incidence and POD-related complications. In this study, we used machine learning techniques to evaluate whether baseline (pre-operative) cognitive function and resting-state electroencephalography could be used to identify patients at risk for POD. Pre-operative resting-state EEGs and the Montreal Cognitive Assessment (MoCA) were collected from 85 patients (age = 73 ± 6.4 years) undergoing elective surgery, 12 of whom subsequently developed POD. The model with the highest f1-score for predicting delirium, a linear-discriminant analysis (LDA) model incorporating MoCA scores and occipital alpha-band EEG features, was subsequently validated in an independent, prospective cohort of 51 older adults (age ≥ 60) undergoing elective surgery, 6 of whom developed POD. The LDA-based model, with a total of 7 features, was able to predict POD with area under the receiver operating characteristic curve, specificity and accuracy all >90%, and sensitivity > 80%, in the validation cohort. Notably, models incorporating both resting-state EEG and MoCA scores outperformed those including either EEG or MoCA alone. While requiring prospective validation in larger cohorts, these results suggest that prediction of POD with high accuracy may be feasible in clinical settings using simple and widely available clinical tools.

  View details for DOI 10.1101/2024.08.15.24312053

  View details for PubMedID 39185530

• Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile x syndrome. Research square Norris, J. E., Berry-Kravis, E. M., Harnett, M. D., Reines, S. A., Reese, M. A., Outterson, A. H., Michalak, C., Furman, J., Gurney, M. E., Ethridge, L. E. 2024

  Abstract

  Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics (PK) and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding in period 1 of the study, participants who received BPN14770 in the period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS.

  View details for DOI 10.21203/rs.3.rs-4474353/v1

  View details for PubMedID 38946987

• Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls ANESTHESIOLOGY Reese, M., Wong, M. K., Cheong, V., Ha, C. I., Wright, M., Browndyke, J., Moretti, E., Devinney, M. J., Habib, A. S., Moul, J. W., Shaw, L. M., Waligorska, T., Whitson, H. E., Cohen, H. J., Welsh-Bohmer, K. A., Plassman, B. L., Mathew, J. P., Berger, M., Markers Alzheimers Dis 2024; 140 (5): 963-978

  Abstract

  Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults.The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid β (Aβ) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls.The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aβ, tau, or p-tau levels, or tau/Aβ or p-tau/Aβ ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (β, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up.During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aβ) changes or greater cognitive decline.

  View details for DOI 10.1097/ALN.0000000000004924

  View details for Web of Science ID 001235375000022

  View details for PubMedID 38324729

  View details for PubMedCentralID PMC11003848

• Preoperative electroencephalographic alpha-power changes with eyes opening are associated with postoperative attention impairment and inattention-related delirium severity BRITISH JOURNAL OF ANAESTHESIA Acker, L., Wong, M. K., Wright, M. C., Reese, M., Giattino, C. M., Roberts, K. C., Au, S., Colon-Emeric, C., Lipsitz, L. A., Devinney, M. J., Browndyke, J., Eleswarpu, S., Moretti, E., Whitson, H. E., Berger, M., Woldorff, M. G., , I. 2024; 132 (1): 154-163

  Abstract

  In the eyes-closed, awake condition, EEG oscillatory power in the alpha band (7-13 Hz) dominates human spectral activity. With eyes open, however, EEG alpha power substantially decreases. Less alpha attenuation with eyes opening has been associated with inattention; thus, we analysed whether reduced preoperative alpha attenuation with eyes opening is associated with postoperative inattention, a delirium-defining feature.Preoperative awake 32-channel EEG was recorded with eyes open and eyes closed in 71 non-neurological, noncardiac surgery patients aged ≥ 60 years. Inattention and other delirium features were assessed before surgery and twice daily after surgery until discharge. Eyes-opening EEG alpha-attenuation magnitude was analysed for associations with postoperative inattention, primarily, and with delirium severity, secondarily, using multivariate age- and Mini-Mental Status Examination (MMSE)-adjusted logistic and proportional-odds regression analyses.Preoperative alpha attenuation with eyes opening was inversely associated with postoperative inattention (odds ratio [OR] 0.73, 95% confidence interval [CI]: 0.57, 0.94; P=0.038). Sensitivity analyses showed an inverse relationship between alpha-attenuation magnitude and inattention chronicity, defined as 'never', 'newly', or 'chronically' inattentive (OR 0.76, 95% CI: 0.62, 0.93; P=0.019). In addition, preoperative alpha-attenuation magnitude was inversely associated with postoperative delirium severity (OR 0.79, 95% CI: 0.65, 0.95; P=0.040), predominantly as a result of the inattention feature.Preoperative awake, resting, EEG alpha attenuation with eyes opening might represent a neural biomarker for risk of postoperative attentional impairment. Further, eyes-opening alpha attenuation could provide insight into the neural mechanisms underlying postoperative inattention risk.

  View details for DOI 10.1016/j.bja.2023.10.037

  View details for Web of Science ID 001165348000001

  View details for PubMedID 38087743

  View details for PubMedCentralID PMC10797508

• Changes in Brain Activity Immediately Post-Exercise Indicate a Role for Central Fatigue in the Volitional Termination of Exercise. International journal of exercise science Chesbro, G. A., Owens, C., Reese, M., DE Stefano, L., Kellawan, J. M., Larson, D. J., Wenger, M. J., Larson, R. D. 2024; 17 (1): 220-234

  Abstract

  Electroencephalography (EEG) allows for the evaluation of real time changes in brain (electrocortical) activity during exercise. A few studies have examined changes in electrocortical activity using stationary cycling, but the findings have been mixed. Some of these studies have found increases in brain activity following exercise, while others have found decreases in brain activity following exercise. Hence, it is of importance to identify post-exercise changes in brain activity. Sixteen healthy, untrained subjects (8 males; 8 females) participated in the study. All 16 participants performed a graded exercise test (GXT) to volitional exhaustion on an upright cycle ergometer. Continuous EEG recordings were sampled before (PRE) and immediately following (IP) the GXT. Regions of interest were primarily the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and left and right motor cortex (MC). In the DLPFC, a frontal asymmetry index was also identified. There was a statistically significant increase in theta power in the DLPFC, VLPFC, and left and right MC from PRE to IP (all p < 0.05). There was also a shift towards right hemisphere asymmetry at the IP time point in the DLPFC (p < 0.05). Finally, there was an increase in alpha power from PRE to IP in the right MC (p < 0.05). EEG could prove to be an important way to measure the effects of central fatigue on brain activity before and immediately following exercise.

  View details for PubMedID 38665161

• EEG pre-burst suppression: characterization and inverse association with preoperative cognitive function in older adults FRONTIERS IN AGING NEUROSCIENCE Reese, M., Christensen, S., Anolick, H., Roberts, K. C., Wong, M. K., Wright, M., Acker, L., Browndyke, J. N., Woldorff, M. G., Berger, M., MADCO-PC & INTUIT Investigators 2023; 15: 1229081

  Abstract

  The most common complication in older surgical patients is postoperative delirium (POD). POD is associated with preoperative cognitive impairment and longer durations of intraoperative burst suppression (BSup) - electroencephalography (EEG) with repeated periods of suppression (very low-voltage brain activity). However, BSup has modest sensitivity for predicting POD. We hypothesized that a brain state of lowered EEG power immediately precedes BSup, which we have termed "pre-burst suppression" (preBSup). Further, we hypothesized that even patients without BSup experience these preBSup transient reductions in EEG power, and that preBSup (like BSup) would be associated with preoperative cognitive function and delirium risk. Data included 83 32-channel intraoperative EEG recordings of the first hour of surgery from 2 prospective cohort studies of patients ≥age 60 scheduled for ≥2-h non-cardiac, non-neurologic surgery under general anesthesia (maintained with a potent inhaled anesthetic or a propofol infusion). Among patients with BSup, we defined preBSup as the difference in 3-35 Hz power (dB) during the 1-s preceding BSup relative to the average 3-35 Hz power of their intraoperative EEG recording. We then recorded the percentage of time that each patient spent in preBSup, including those without BSup. Next, we characterized the association between percentage of time in preBSup and (1) percentage of time in BSup, (2) preoperative cognitive function, and (3) POD incidence. The percentage of time in preBSup and BSup were correlated (Spearman's ρ [95% CI]: 0.52 [0.34, 0.66], p < 0.001). The percentage of time in BSup, preBSup, or their combination were each inversely associated with preoperative cognitive function (β [95% CI]: -0.10 [-0.19, -0.01], p = 0.024; -0.04 [-0.06, -0.01], p = 0.009; -0.04 [-0.06, -0.01], p = 0.003, respectively). Consistent with prior literature, BSup was significantly associated with POD (odds ratio [95% CI]: 1.34 [1.01, 1.78], p = 0.043), though this association did not hold for preBSup (odds ratio [95% CI]: 1.04 [0.95, 1.14], p = 0.421). While all patients had ≥1 preBSup instance, only 20.5% of patients had ≥1 BSup instance. These exploratory findings suggest that future studies are warranted to further study the extent to which preBSup, even in the absence of BSup, can identify patients with impaired preoperative cognition and/or POD risk.

  View details for DOI 10.3389/fnagi.2023.1229081

  View details for Web of Science ID 001066341900001

  View details for PubMedID 37711992

  View details for PubMedCentralID PMC10499509

• Perioperative changes in neurocognitive and Alzheimer's disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance BRITISH JOURNAL OF ANAESTHESIA Villalobos, D., Reese, M., Wright, M., Wong, M., Syed, A., Park, J., Hall, A., Browndyke, J. N., Martucci, K. T., Devinney, M. J., Acker, L., Moretti, E. W., Talbot, L., Colin, B., Ohlendorf, B., Waligorska, T., Shaw, L. M., Whitson, H. E., Cohen, H. J., Mathew, J. P., Berger, M. 2023; 131 (2): 328-337

  Abstract

  Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans.This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively.There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aβ), tau, or phospho-tau181p levels, or on the tau/Aβ or p-tau181p/Aβ ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses.Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults.NCT01993836.

  View details for DOI 10.1016/j.bja.2023.04.019

  View details for Web of Science ID 001148259700001

  View details for PubMedID 37271721

  View details for PubMedCentralID PMC10375507

• A Real-Time Neurophysiologic Stress Test for the Aging Brain: Novel Perioperative and ICU Applications of EEG in Older Surgical Patients NEUROTHERAPEUTICS Berger, M., Ryu, D., Reese, M., McGuigan, S., Evered, L. A., Price, C. C., Scott, D. A., Westover, M., Eckenhoff, R., Bonanni, L., Sweeney, A., Babiloni, C. 2023; 20 (4): 975-1000

  Abstract

  As of 2022, individuals age 65 and older represent approximately 10% of the global population [1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [2, 3]. With approximately > 234 million major surgical procedures performed annually worldwide [4], this suggests that > 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [5], greater economic burden [6, 7], and greater risk for developing long-term cognitive decline [8] such as Alzheimer's disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological "stress test" for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline (see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient "passed" or "failed" this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a "predictor" of delirium and perioperative cognitive decline in older surgical patients.

  View details for DOI 10.1007/s13311-023-01401-4

  View details for Web of Science ID 001028417900002

  View details for PubMedID 37436580

  View details for PubMedCentralID PMC10457272

• Intraoperative Anesthetic Probes of Brain Health: Ketamine as a Canary in the Coal Mine? Anesthesia and analgesia Reese, M., Heifets, B. D., Berger, M. 2022; 135 (4): 679-682

  View details for DOI 10.1213/ANE.0000000000005965

  View details for PubMedID 36108180

• Machine learning XGBoost classification of postoperative delirium by intraoperative EEG metrics Reese, M., Roberts, K., Woldorff, M. G., Cooter, M., Acker, L., Wu, S., Whitson, H. E., Berger, M. LIPPINCOTT WILLIAMS & WILKINS. 2022: 609-611

  View details for Web of Science ID 000840283000244

• Cognitive and cerebrospinal fluid Alzheimer's Disease biomarker changes over time in older surgical patients and matched nonsurgical controls Wong, M., Reese, M., Cooter, M., Browndyke, J. N., Mathew, J. P., Cohen, H. J., Whitson, H. E., Berger, M. LIPPINCOTT WILLIAMS & WILKINS. 2022: 954-956

  View details for Web of Science ID 000840283001065

• Preoperative EEG Inattention Signatures and Postoperative Delirium Acker, L., Au, S., Roberts, K., Giattino, C., Moretti, E., Devinney, M., Reese, M., Cohen, H. J., Mathew, J. P., Woldorff, M. G., Whitson, H. E., Berger, M. LIPPINCOTT WILLIAMS & WILKINS. 2022: 496

  View details for Web of Science ID 000840283000190

• Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY Berger, M., Browndyke, J. N., Wright, M., Nobuhara, C., Reese, M., Acker, L., Bullock, W., Colin, B. J., Devinney, M. J., Moretti, E. W., Moul, J. W., Ohlendorf, B., Laskowitz, D. T., Waligorska, T., Shaw, L. M., Whitson, H. E., Cohen, H. J., Mathew, J. P., MADCO-PC Investigators 2022; 9 (2): 155-170

  Abstract

  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.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.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).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).clinicaltrials.gov (NCT01993836).

  View details for DOI 10.1002/acn3.51499

  View details for Web of Science ID 000749251400001

  View details for PubMedID 35104057

  View details for PubMedCentralID PMC8862419