Dynamic contrast-enhanced magnetic resonance imaging perfusion characteristics in meningiomas treated with resection and adjuvant radiosurgery.

OBJECTIVEThere is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.METHODSA retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (vp), extracellular volume (ve), volume transfer constant (Ktrans), rate constant (kep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.RESULTSThe mean patient age was 64 years (range 49-86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21-27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median vp (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec-1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between ve and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between Ktrans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).CONCLUSIONSThis study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.

Intraoperative augmented reality fiber tractography complements cortical and subcortical mapping.

Augmented reality (AR) has been found to be advantageous in enhancing visualization of complex neuroanatomy intraoperatively and in neurosurgical education. Another key tool that allows neurosurgeons to have enhanced visualization, namely of white matter tracts, is diffusion tensor imaging (DTI) that is processed with high-definition fiber tractography (HDFT). There remains an enduring challenge in the structural-functional correlation of white matter tracts that centers on the difficulty in clearly assigning function to any given fiber tract when evaluating them through separated as opposed to integrated modalities. Combining the technologies of AR with fiber tractography shows promise in helping to fill in this gap between structural-functional correlation of white matter tracts. This novel study demonstrates through a series of three cases of awake craniotomies for glioma resections a technique that allows the first and most direct evidence of fiber tract stimulation and assignment of function or deficit in vivo through the intraoperative, real-time fusion of electrical cortical stimulation, AR, and HDFT. This novel technique has qualitatively shown to be helpful in guiding intraoperative decision making on extent of resection of gliomas. Future studies could focus on larger, prospective cohorts of glioma patients who undergo this methodology and further correlate the post-operative imaging results to patient functional outcomes.

The use of mixed reality for the treatment planning of unruptured intracranial aneurysms.

BACKGROUND: A thorough comprehension of topographic neuroanatomy is paramount in neurosurgery. In recent years, great attention has been raised towards extended reality, which comprises virtual, augmented, and mixed reality (MR) as an aid for surgery. In this paper, we describe our preliminary experience with the use of a new MR platform, aiming to assess its reliability and usefulness in the planning of surgical treatment of unruptured intracranial aneurysms. METHODS: We prospectively enrolled 5 patients, harboring a total of 8 intracranial unruptured aneurysms, undergoing elective surgical clipping. A wearable mixed-reality device (HoloLens; Microsoft Corp., Redmond, WA, USA) was used to display and interact with a holographic model during surgical planning. Afterward, a total of 10 among surgeons and residents filled in a 5-point Likert-Scale evaluation questionnaire. RESULTS: According to the participants' feedback, the main MR platform advantages were considered the educational value, its utility during patients positioning and craniotomy planning, as well as the anatomical and imaging interpretation during surgery. The graphic performance was also deemed very satisfactory. On the other hand, the device was evaluated as not easy to use and pretty uncomfortable when worn for a long time. CONCLUSIONS: We demonstrated that MR could play important role in planning the surgical treatment of intracranial aneurysms by enhancing the visualization and understanding of the patient-specific anatomy.

Dr. Thanjavur Santhanakrishna Kanaka-A Pioneer and Neurosurgical Innovator.

BACKGROUND: Thanjavur Santhanakrishna Kanaka, M.B.B.S., M.S. (General Surgery), M.S. (Neurosurgery), Ph.D., and former Captain, Indian Army Medical Corps, was born on March 31, 1932. She became the first woman neurosurgeon in India and all of Asia. METHODS: This manuscript was compiled through a combination of interviews and references to other articles and some of the published manuscripts of Dr. Kanaka and her colleagues. RESULTS: Dr. Kanaka was a trailblazer for women in neurosurgery and a pioneer in functional and stereotactic neurosurgery. During her long and productive career, she authored dozens of articles reported in prestigious neurosurgical journals worldwide and helped inspire and train the next generations of neurosurgeons in India and abroad. Even after retirement, Dr. Kanaka continued to focus on serving the medical community through her Sri Santhanakrishna Padmavathi Health Care and Research Foundation in Chennai with the mission of serving underprivileged and senior citizens in the local community. In addition to her accomplishments as a practicing neurosurgeon, Dr. Kanaka's career was notable for her successful collaborations with biomedical engineers on medical device development using locally sourced materials and talent in India. CONCLUSIONS: Through her innovative thinking, compassion for her patients, and unwavering resilience, Dr. Kanaka has continued to serve as an inspiration to all pursuing a career in academic medicine and neurosurgery.

Elastic Image Fusion Software to Coregister Preoperatively Planned Pedicle Screws With Intraoperative Computed Tomography Data for Image-Guided Spinal Surgery.

BACKGROUND: For complex spinal cases, especially when robotic guidance is used, preoperative planning of pedicle screws can be helpful. Transfer of these preoperatively planned pedicle screws to intraoperative 3-dimensional imaging is challenging because of changes in anatomic alignment between preoperative supine and intraoperative prone imaging, especially when multiple levels are involved. In the spine, where each individual vertebra is subject to independent movement from adjacent level, rigid image fusion is confined to a single vertebra and can display fusion inaccuracies on adjacent levels. A novel elastic fusion algorithm is introduced to overcome these disadvantages. This study aimed to investigate image registration accuracy of preoperatively planned pedicle screws with an elastic fusion algorithm vs. rigid fusion for intraoperative placement with image-guided surgery. METHODS: A total of 12 patients, were selected depending on the availability of a preoperative spinal computed tomography (CT) and an intraoperative AIRO CT scan (BrainLAB AG, Munich, Germany) of the same spinal region. To verify accuracy differences between rigid fusion and elastic fusion 76 bilateral screw trajectories were virtually defined in the preoperative CT image, and they were transferred via either rigid fusion or elastic fusion to the intraoperative CT scan. Accuracy of the transferred screws in the rigid and elastic fusion group was determined by measuring pedicle breaches on the intraoperative CT. RESULTS: In the rigid fusion group 1.3% of screws showed a breach of less than 2 mm, 9.2% showed breaches between 2 and 4 mm, and 18.4% of the screws showed an error above 4 mm. The elastic fusion group showed no breaches and provided high accuracy between preoperative and intraoperative screw placement. CONCLUSION: Elastic fusion provides high registration accuracy and represents a considerable step towards efficiency and safety in CT-based image-guided surgery. LEVEL OF EVIDENCE: 3.

Evidence-based practice of stereotactic radiosurgery: Outcomes from an educational course for neurosurgery and radiation oncology residents.

BACKGROUND: As the field of brain and spine stereotactic radiosurgery (SRS) continues to grow, so will the need for a comprehensive evidence base. However, it is unclear to what degree trainees feel properly equipped to use SRS. We assess the perceptions and comfort level reported by neurosurgery and radiation oncology residents concerning the evidence-based practice of SRS. METHODS: A continuing medical education (CME) course provided peer-reviewed updates regarding treatment with intracranial and spinal SRS. Presentations were given by neurosurgery and radiation oncology residents with mentorship by senior faculty. To gauge perceptions regarding SRS, attendees were surveyed. Responses before and after the course were analyzed using the Fisher's exact test in R statistical software. RESULTS: Participants reported the greatest knowledge improvements concerning data registries (P < 0.001) and clinical trials (P = 0.026). About 82% of all (n = 17) radiation oncology and neurosurgery residents either agreed or strongly agreed that a brain and spine SRS rotation would be beneficial in their training. However, only 47% agreed or strongly agreed that one was currently part of their training. In addition, knowledge gains in SRS indications (P = 0.084) and ability to seek collaboration with colleagues (P = 0.084) showed notable trends. CONCLUSION: There are clear knowledge gaps shared by potential future practitioners of SRS. Specifically, knowledge regarding SRS data registries, indications, and clinical trials offer potential areas for increased educational focus. Furthermore, the gap between enthusiasm for increased SRS training and the current availability of such training at medical institutions must be addressed.

Applications of augmented reality in the neurosurgical operating room: A systematic review of the literature.

Advancements in imaging techniques are key forces of progress in neurosurgery. The importance of accurate visualization of intraoperative anatomy cannot be overemphasized and is commonly delivered through traditional neuronavigation. Augmented Reality (AR) technology has been tested and applied widely in various neurosurgical subspecialties in intraoperative, clinical use and shows promise for the future. This systematic review of the literature explores the ways in which AR technology has been successfully brought into the operating room (OR) and incorporated into clinical practice. A comprehensive literature search was performed in the following databases from inception-April 2020: Ovid MEDLINE, Ovid EMBASE, and The Cochrane Library. Studies retrieved were then screened for eligibility against predefined inclusion/exclusion criteria. A total of 54 articles were included in this systematic review. The studies were sub- grouped into brain and spine subspecialties and analyzed for their incorporation of AR in the neurosurgical clinical setting. AR technology has the potential to greatly enhance intraoperative visualization and guidance in neurosurgery beyond the traditional neuronavigation systems. However, there are several key challenges to scaling the use of this technology and bringing it into standard operative practice including accurate and efficient brain segmentation of magnetic resonance imaging (MRI) scans, accounting for brain shift, reducing coregistration errors, and improving the AR device hardware. There is also an exciting potential for future work combining AR with multimodal imaging techniques and artificial intelligence to further enhance its impact in neurosurgery.

Assessing the long-term safety and efficacy of gamma knife and linear accelerator radiosurgery for vestibular schwannoma: A systematic review and meta-analysis.

BACKGROUND: Differences in long-term outcomes of single-fraction stereotactic radiosurgery (SRS) between gamma knife (GK) and linear accelerator (LINAC) systems for vestibular schwannoma (VS) management remain unclear. To investigate differences in safety and efficacy between modalities, we conducted a meta-analysis of studies over the past decade. METHODS: MEDLINE, EMBASE, and Cochrane databases were queried for studies with the following inclusion criteria: English language, published between January 2010 and April 2020, cohort size ≥30, and mean/median follow-up ≥5 years. Odds ratios (OR) compared rates of tumor control, hearing preservation, and cranial nerve toxicities before and after SRS. RESULTS: Thirty-nine studies were included (29 GK, 10 LINAC) with 6516 total patients. Tumor control rates were 93% (95% CI 91-94%) and 94% (95% CI 91-97%) for GK and LINAC, respectively. Both GK (OR 0.06, 95% CI 0.02-0.13) and LINAC (OR 0.47, 95% CI 0.29-0.76) reduced odds of serviceable hearing. Neither GK (OR 0.71, 95% CI 0.41-1.22) nor LINAC (OR 1.13, 95% CI 0.64-2.00) impacted facial nerve function. GK decreased odds of trigeminal nerve (TN) impairment (OR 0.55, 95% CI 0.32-0.94) while LINAC did not impact TN function (OR 1.45, 95% CI 0.81-2.61). Lastly, LINAC offered decreased odds of tinnitus (OR 0.15, 95% CI 0.03-0.87) not observed with GK (OR 0.70, 95% CI 0.48-1.01). CONCLUSIONS: VS tumor control and hearing preservation rates are comparable between GK and LINAC SRS. GK may better preserve TN function, while LINAC decreases tinnitus rates. Future studies are warranted to investigate the efficacy of GK and LINAC SRS more directly.

The World of Neurosurgery Reimagined Post COVID-19: Crisis ↔ Opportunities.

The COVID-19 pandemic has impacted neurosurgery in unforeseeable ways. Neurosurgical patient care, research, and education have undergone extraordinary modifications as medicine and mankind have adapted to overcome the challenges posed by this pandemic. Some changes will disappear as the situation slowly recovers to a prepandemic status quo. Others will remain: This pandemic has sparked some long-overdue systemic transformations across all levels of medicine, including in neurosurgery, that will be beneficial in the future. In this paper, we present some of the challenges faced across different levels of neurosurgical clinical care, research, and education, the changes that followed, and how some of these modifications have transformed into opportunities for improvement and growth in the future.

Alopecia following cranial stereotactic radiosurgery: A comprehensive review of the literature.

Alopecia is often an undesirable side effect for patients undergoing radiation treatment. Although prophylaxis has been studied for alopecia following radiotherapy and chemotherapy, little research has been done in preventing radiosurgery induced alopecia. Past studies have found that increasing the dose of radiation delivered increases the degree of alopecia by generating a late regenerative response by the hair follicles (HFs). Various studies showed that using hair sparing techniques such as IMRT, VMAT, and HS-WBRT decreases the amount of dose to the scalp, thereby reducing hair loss. It has also been found that the location of the scalp with the highest degree of alopecia is that which is closest to area of greatest dose overlap. Accordingly, preventing dose overlap with arcs or cerrobend blocks has been shown to decrease alopecia. It has also been reported that hair loss is found in the area closer to the contour arcs where the dose is highest. We have reviewed the existing data on the prevention and treatment of radiation-induced alopecia and have presented here a comprehensive review of the reported data and relevant clinical considerations relating to dose, location, and scalp surface area (SSA).

Pseudohypoxic Brain Swelling After Uncomplicated Lumbar Decompression and Fusion for Spondylolisthesis.

BACKGROUND: Pseudohypoxic brain swelling (PHBS), also known as postoperative intracranial hypotension-associated venous congestion, is a rare complication after neurosurgery characterized by rapid and often severe postoperative deterioration in consciousness and distinct imaging findings on brain magnetic resonance imaging. Imaging findings associated with PHBS include computed tomography and magnetic resonance imaging findings that resemble hypoxic changes and intracranial hypotensive changes in basal ganglia and thalamus, telencephalic, and infratentorial regions without notable changes in intracranial vasculature. CASE DESCRIPTION: This report describes the case of an L4-5 microdiskectomy with posterior decompression and fusion complicated by clinical and radiographic findings resembling PHBS without a known intraoperative durotomy. CONCLUSIONS: Spine surgeons should be alerted to the possibility that PHBS may occur in patients even after an operation without known durotomy or cerebrospinal fluid leakage and with spontaneous clinical resolution unrelated to suction drainage changes or epidural blood patches.

Clinical Considerations in Neurosurgical Radiosurgery in the Time of COVID-19.

The COVID-19 pandemic is affecting all aspects of the healthcare ecosystem, including administration of stereotactic radiosurgery (SRS). The clinical and logistical challenges created by the COVID-19 public health crisis are clear, but the solutions to these issues are less readily apparent. The goal of this work is to use our experience at a large, academic medical center as a lens for interpreting the many looming issues specific to radiosurgery and its role in the treatment of brain and spine disorders. While the full impact of the pandemic remains to be seen, the aim of this paper is to provide a structural framework to optimize delivery of neurosurgically oriented radiosurgery with proposed clinical workflow strategies. Innovative solutions to the current pandemic crisis affecting the healthcare ecosystem will be driven by increased interdisciplinary and global dialogue.

Reirradiation of Recurrent Brain Metastases: Where Do We Stand?

Brain metastases occur in a large portion of patients with cancer. Although advances in radiotherapy have helped to improve survival, they have also raised questions regarding the best modality for retreatment in the context of recurrent disease. The spectrum of treatment options for recurrent intracranial metastatic disease after previous radiotherapy includes salvage stereotactic radiosurgery, whole brain radiotherapy, and brachytherapy. We have comprehensively reviewed the existing data on the efficacy and toxicity of the various reirradiation treatment modalities. We examined the key clinical considerations that guide patient selection, such as dose, tumor size, interval to retreatment, and local control and survival rates.

A Multidisciplinary Team Approach to Brain and Spine Stereotactic Radiosurgery Conferences: A Unique Institutional Model.

OBJECTIVE: The use of multidisciplinary teams (MDTs) comprised of all members of the patient care team is becoming increasingly popular in the field of oncology. We present a single-center experience exploring the utility and uniqueness of an MDT in the care of patients undergoing brain and spine stereotactic radiosurgery (SRS). METHODS: The weekly SRS conference brought together neurosurgeons, radiation oncologists, neuroradiologists, physicists, dosimetrists, therapists, advanced practice providers, and trainees in these fields as well as researchers from a variety of disciplines with a goal of optimizing patient care. A survey of 20 conference attendees from 7 different facets of the MDT was conducted for feedback. RESULTS: The survey results revealed that most respondents believed the SRS conference increased educational opportunities, provided opportunities for research and collaborations, helped streamline patient care, and was beneficial to their practice. CONCLUSIONS: We present our institutional MDT model, a framework and workflow that can be incorporated at other large academic centers. We believe that the SRS conference has educational, academic, and patient care value.

Worldwide Access to Stereotactic Radiosurgery.

Stereotactic radiosurgery is a safe and effective technology that can address a variety of neurosurgical conditions, but in many parts of the world, access remains an issue. Although the technology is increasingly available in the United States, Canada, Europe, and parts of Asia, poor access to central nervous system (CNS) imaging and inadequate treatment equipment in other parts of the world limit the availability of radiosurgery as a treatment option. In addition, epidemiologic data about cancer and CNS metastases in low-income countries are sparse and much less complete than in more developed countries, and the need for radiosurgery may be underestimated as a result. Current radiosurgical platforms can be expensive to install and require a substantial amount of personnel training for safe operation. Socioeconomic and political forces are relevant to limitations to and opportunities for improving access to care. Here we examine the current barriers to access and propose areas for future efforts to improve global availability of radiosurgery for neurosurgical conditions.

Impact of Operating Room Environment on Postoperative Central Nervous System Infection in a Resource-Limited Neurosurgical Center in South Asia.

BACKGROUND: Postoperative central nervous system infections (PCNSIs) are serious complications following neurosurgical intervention. We previously investigated the incidence and causative pathogens of PCNSIs at a resource-limited, neurosurgical center in south Asia. This follow-up study was conducted to analyze differences in PCNSIs at the same institution following only one apparent change: the operating room air filtration system. METHODS: This was a retrospective study of all neurosurgical cases performed between December 1, 2013, and March 31, 2016 at our center. Providers, patient demographic data, case types, perioperative care, rate of PCNSI, and rates of other complications were reviewed. These results were then compared with the findings of our previous study of neurosurgical cases between June 1, 2012, and June 30, 2013. RESULTS: All 623 neurosurgical operative cases over the study period were reviewed. Four patients (0.6%) had a PCNSI, and no patients had a positive cerebrospinal fluid (CSF) culture. In the previous study, among 363 cases, 71 patients (19.6%) had a PCNSI and 7 (1.9%) had a positive CSF culture (all Gram-negative organisms). The differences in both parameters are statistically significant (P < 0.001). Between the 2 studies, there was no change in treatment providers, case types, case durations, antibiotic administration practices, and patient demographics. CONCLUSIONS: The rates of PCNSI and positive CSF culture were significantly lower in our present cohort compared with the cohort in our previous study. The sole apparent change involves the air filtration system inside the neurosurgical operating rooms; this environmental change occurred during the 5 months between the 2 studies. This study demonstrates the impact of environmental factors in reducing infections.

Vertebral-venous fistula: an unusual cause for ocular symptoms mimicking a carotid cavernous fistula.

Vertebral-venous fistulas (VVF), or vertebral-vertebral arteriovenous fistulas, are an uncommon clinical entity. Typically, they present as a result of a direct vascular connection between an extracranial branch of the vertebral artery or its radicular components and the epidural venous plexus. These may manifest with signs and symptoms referable to cervical myelopathy secondary to compression or steal phenomenon. To our knowledge, this is the first case to identify a patient who presented with classic ocular symptoms attributable to a carotid cavernous fistula but secondary to a VVF. We present its treatment and clinical outcome. In addition, we present a brief literature review surrounding this uncommon disease.

Postoperative Central Nervous System Infection After Neurosurgery in a Modernized, Resource-Limited Tertiary Neurosurgical Center in South Asia.

OBJECTIVE: Postoperative central nervous system infections (PCNSIs) are rare but serious complications after neurosurgery. The purpose of this study was to examine the prevalence and causative pathogens of PCNSIs at a modernized, resource-limited neurosurgical center in South Asia. METHODS: A retrospective analysis was conducted of the medical records of all 363 neurosurgical cases performed between June 1, 2012, and June 30, 2013, at a neurosurgical center in South Asia. Data from all operative neurosurgical cases during the 13-month period were included. RESULTS: Cerebrospinal fluid (CSF) analysis indicated that 71 of the 363 surgical cases had low CSF glucose or CSF leukocytosis. These 71 cases were categorized as PCNSIs. The PCNSIs with positive CSF cultures (9.86%) all had gram-negative bacteria with Pseudomonas aeruginosa (n = 5), Escherichia coli (n = 1), or Klebsiella pneumoniae (n = 1). The data suggest a higher rate of death (P = 0.031), a higher rate of CSF leak (P < 0.001), and a higher rate of cranial procedures (P < 0.001) among the infected patients and a higher rate of CSF leak among the patients with culture-positive infections (P = 0.038). CONCLUSIONS: This study summarizes the prevalence, causative organism of PCNSI, and antibiotic usage for all of the neurosurgical cases over a 13-month period in a modernized yet resource-limited neurosurgical center located in South Asia. The results from this study highlight the PCNSI landscape in an area of the world that is often underreported in the neurosurgical literature because of the paucity of clinical neurosurgical research undertaken there. This study shows an increasing prevalence of gram-negative organisms in CSF cultures from PCNSIs, which supports a trend in the recent literature of increasing gram-negative bacillary meningitis.

Vertebral-venous fistula: an unusual cause for ocular symptoms mimicking a carotid cavernous fistula.

Vertebral-venous fistulas (VVF), or vertebral-vertebral arteriovenous fistulas, are an uncommon clinical entity. Typically, they present as a result of a direct vascular connection between an extracranial branch of the vertebral artery or its radicular components and the epidural venous plexus. These may manifest with signs and symptoms referable to cervical myelopathy secondary to compression or steal phenomenon. To our knowledge, this is the first case to identify a patient who presented with classic ocular symptoms attributable to a carotid cavernous fistula but secondary to a VVF. We present its treatment and clinical outcome. In addition, we present a brief literature review surrounding this uncommon disease.

Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer's Disease.

We recently documented plasma lipid dysregulation in preclinical late-onset Alzheimer's disease (LOAD). A 10 plasma lipid panel, predicted phenoconversion and provided 90% sensitivity and 85% specificity in differentiating an at-risk group from those that would remain cognitively intact. Despite these encouraging results, low positive predictive values limit the clinical usefulness of this panel as a screening tool in subjects aged 70-80 years or younger. In this report, we re-examine our metabolomic data, analyzing baseline plasma specimens from our group of phenoconverters (n = 28) and a matched set of cognitively normal subjects (n = 73), and discover and internally validate a panel of 24 plasma metabolites. The new panel provides a classifier with receiver operating characteristic area under the curve for the discovery and internal validation cohort of 1.0 and 0.995 (95% confidence intervals of 1.0-1.0, and 0.981-1.0), respectively. Twenty-two of the 24 metabolites were significantly dysregulated lipids. While positive and negative predictive values were improved compared to our 10-lipid panel, low positive predictive values provide a reality check on the utility of such biomarkers in this age group (or younger). Through inclusion of additional significantly dysregulated analyte species, our new biomarker panel provides greater accuracy in our cohort but remains limited by predictive power. Unfortunately, the novel metabolite panel alone may not provide improvement in counseling and management of at-risk individuals but may further improve selection of subjects for LOAD secondary prevention trials. We expect that external validation will remain challenging due to our stringent study design, especially compared with more diverse subject cohorts. We do anticipate, however, external validation of reduced plasma lipid species as a predictor of phenoconversion to either prodromal or manifest LOAD.