Intracranial meningioma: A review of recent and emerging data on the utility of preoperative imaging for management.

Meningiomas are the most common neoplasms of the central nervous system, accounting for approximately 40% of all brain tumors. Surgical resection represents the mainstay of management for symptomatic lesions. Preoperative planning is largely informed by neuroimaging, which allows for evaluation of anatomy, degree of parenchymal invasion, and extent of peritumoral edema. Recent advances in imaging technology have expanded the purview of neuroradiologists, who play an increasingly important role in meningioma diagnosis and management. Tumor vascularity can now be determined using arterial spin labeling and dynamic susceptibility contrast-enhanced sequences, allowing the neurosurgeon or neurointerventionalist to assess patient candidacy for preoperative embolization. Meningioma consistency can be inferred based on signal intensity; emerging machine learning technologies may soon allow radiologists to predict consistency long before the patient enters the operating room. Perfusion imaging coupled with magnetic resonance spectroscopy can be used to distinguish meningiomas from malignant meningioma mimics. In this comprehensive review, we describe key features of meningiomas that can be established through neuroimaging, including size, location, vascularity, consistency, and, in some cases, histologic grade. We also summarize the role of advanced imaging techniques, including magnetic resonance perfusion and spectroscopy, for the preoperative evaluation of meningiomas. In addition, we describe the potential impact of emerging technologies, such as artificial intelligence and machine learning, on meningioma diagnosis and management. A strong foundation of knowledge in the latest meningioma imaging techniques will allow the neuroradiologist to help optimize preoperative planning and improve patient outcomes.

Contrast-enhanced ultrasound (CEUS) for the characterization of intra-scrotal lesions.

Contrast-enhanced ultrasound (CEUS) has emerged as a promising imaging modality for the characterization of hepatic and renal lesions. However, there is a paucity of data describing the use of CEUS for the evaluation of intra-scrotal pathology. In the following review, we describe the clinical utility of CEUS for the characterization and differentiation of common and uncommon intra-scrotal conditions, including testicular torsion, infection, trauma, and benign and malignant intratesticular and extratesticular neoplasms. In addition, we outline key principles of CEUS and provide case examples from our institution.

Current Trends and Applications of PET/MRI Hybrid Imaging in Neurodegenerative Diseases and Normal Aging.

Dementia is a significant global health issue that is exacerbated by an aging population. Imaging plays an established role in the evaluation of patients with neurocognitive disorders such as dementia. In current clinical practice, magnetic resonance imaging (MRI) and positron emission tomography (PET) are primary imaging modalities used separately but in concert to help diagnose and classify dementia. The clinical applications of PET/MRI hybrid imaging in dementia are an active area of research, particularly given the continued emergence of functional MRI (fMRI) and amyloid PET tracers. This narrative review provides a comprehensive overview of the rationale and current evidence for PET/MRI hybrid dementia imaging from 2018 to 2023. Hybrid imaging offers advantages in the accuracy of characterizing neurodegenerative disorders, and future research will need to address the cost of integrated PET/MRI systems compared to stand-alone scanners, the development of new biomarkers, and image correction techniques.

Clinical Applications of PET in Evaluating the Aging Spine.

Back pain is a common health complaint that contributes globally to medical burden and costs, particularly in elderly populations. Nuclear medicine techniques using PET tracers offer diagnostic information about various spine disorders, including malignant, degenerative, inflammatory, and infectious diseases. Herein, the authors briefly review applications of PET in the evaluation of spine disorders in elderly patients.

Safety and feasibility of urological procedures in Jehovah's Witness patients.

OBJECTIVES: To describe the safety and feasibility of urological transfusion-free surgeries in Jehovah's Witness patients. METHODS: An institutional review board-approved, retrospective review of Jehovah's Witness patients who underwent urological transfusion-free surgeries between 2003 and 2019 was carried out. Surgeries were stratified into low, intermediate and high risk based on complexity, invasiveness and bleeding potential. Patient demographics, perioperative data and clinical outcomes are reported. RESULTS: A total of 161 Jehovah's Witness patients (median age 63.4 years) underwent 171 transfusion-free surgeries, including 57 (33.3%) in low-, 82 (47.9%) in intermediate- and 32 (18.8%) in high-risk categories. The mean estimated blood loss increased with risk category at 48 mL (range 10-50 mL), 150 mL (range 50-200 mL) and 388 mL (range 137-500 mL), respectively (P < 0.001). Implementing blood augmentation and conservation techniques increased with each risk category (3.5% vs 29% vs 69%, respectively; P < 0.001). Average length of stay increased concordantly at 1.6 days (range 0-12 days), 2.9 days (range 1-13 days) and 5.6 days (range 2-12 days), respectively (P ≤ 0.001). However, there was no increase in complication rates and readmission rates attributed to bleeding among the risk categories at 30 days (P = 0.9 and 0.4, respectively) and 90 days (P = 0.7 and 0.7, respectively). CONCLUSIONS: Transfusion free urological surgery can be safely carried out on Jehovah's Witness patients using contemporary perioperative optimization. Additionally, these techniques can be expanded for use in the general patient population to avoid short- and long-term consequences of perioperative blood transfusion.

Surgical approach as a determinant factor of clinical outcome following radical cystectomy: Does Enhanced Recovery After Surgery (ERAS) level the playing field?

PURPOSE: To determine whether surgical approach is a determinant of clinical outcomes following radical cystectomy (RC) and urinary diversion when using an Enhanced Recovery After Surgery (ERAS) protocol. MATERIALS AND METHODS: We studied all patients undergoing both open radical cystectomy (ORC) and robotic-assisted radical cystectomy (RARC) and urinary diversion with ERAS for bladder urothelial carcinoma from May 2012 to December 2016. Surgical and clinical outcomes within 90 days after surgery were compared between ORC and RARC, including readmission and major complication rates (Clavien-Dindo grade ≥III). Multivariable logistic regression modeling was used to determine factors that predict readmission and major complications. RESULTS: A total of 345 and 143 patients underwent ORC and RARC, respectively. The ORC group had a greater proportion of continent urinary diversion (71.9 vs. 40.6%, P< 0.001), shorter operative time (5.4 vs. 7.3 hours, P< 0.001), higher estimated blood loss (500 vs. 200 ml, P< 0.001), and higher intraoperative and postoperative transfusion rates (20.9 vs. 9.1%, P= 0.002 and 20 vs. 11.9%, P= 0.04, respectively). Median length of stay was 4 days for ORC (interquartile range 4-6 days) and 6 days for RARC (interquartile range 4-7 days; P< 0.001). There was no significant difference between ORC and RARC groups in major complication rates (20 vs. 23.8%, P= 0.51) or readmission rates (32.2 vs. 36.4%, P= 0.4) within 90 days after surgery. Multivariable logistic regression analysis showed that surgical approach was not an independent factor predictive of readmission (P= 0.33) or major complications (P= 0.76). CONCLUSIONS: Surgical approach is not a determinant of readmission or major complications following RC in the context of an ERAS protocol.

Long term oncologic outcome in patients with bladder cancer after radical cystectomy: Impact of carcinoma in situ in the era of neoadjuvant chemotherapy.

PURPOSE: To assess the impact of carcinoma in situ (CIS) on oncologic outcomes in patients who underwent radical cystectomy, with a focus on those who received neoadjuvant chemotherapy (NAC) including patients with down-staging to ≤ pT1cancer after chemotherapy. MATERIALS AND METHODS: All patients who underwent radical cystectomy for urothelial cancer with curative intent from 1985 to 2011 were included. The impact of CIS on recurrence free and overall survival (OS) was assessed in the whole cohort and a subgroup who received NAC as well as those with response to chemotherapy and down-staging to ≤ pT1. RESULTS: A total of 2518 patients with a median follow-up period of 9 years were included. Among all, 1397 (55.5%) had concomitant CIS on final pathology. CIS was associated with high risk pathologic features including high-grade disease, multifocality, and nodal involvement as well as worse recurrence free survival (RFS) with no impact on OS. We did not find a significant association between CIS and oncologic outcomes in a subset of patients who received NAC including those with down-staging to ≤ pT1 disease. In multivariate analysis, CIS had no association with either recurrence free or OS. CONCLUSIONS: Concomitant CIS in radical cystectomy specimens is associated with decreased RFS; however, in multivariate analysis, it was not an independent predicting factor of oncologic outcomes. Moreover, the impact of CIS on oncologic outcomes in a subset of patients who received NAC was insignificant.

Association between precystectomy epithelial tumor marker response to neoadjuvant chemotherapy and oncological outcomes in urothelial bladder cancer.

INTRODUCTION AND OBJECTIVES: We previously reported that elevated precystectomy serum levels of epithelial tumor markers predict worse oncological outcome in patients with invasive bladder cancer (BC). Herein, we evaluated the effect of neoadjuvant chemotherapy (NAC) on elevated tumor marker levels and their association with oncological outcomes. METHODS: Under IRB approval, serum levels of Carbohydrate Antigen 125 (CA-125), Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) were prospectively measured in 480 patients with invasive BC from August 2011 through December 2016. In the subgroup undergoing NAC, markers were measured prior to the first and after the last cycle of chemotherapy (prior to cystectomy). RESULTS: Three hundred and thirty-seven patients were eligible for the study, with a median age was 71 years (range 34-93) and 81% (272) male. Elevated precystectomy level of any tumor markers (31% of patients) was independently associated with worse recurrence-free survival (hazard ratio [HR] = 2.81; P < 0.001) and overall survival (HR = 3.97; P < 0.001). One hundred and twenty-five (37%) patients underwent NAC, of whom 59 had a complete tumor marker profile and 30 (51%) had an elevated pre-NAC tumor marker. Following completion of chemotherapy, 10/30 (33%) patients normalized their tumor markers, while 20/30 (67%) had one or more persistently elevated markers. There was no difference in clinical or pathological stage between groups (P = 0.54 and P = 0.09, respectively). Further analysis showed a significantly lower rate and longer median time to recurrence/progression in the responder group (50% in responders vs. 90% in nonresponders at a median time of 22 vs. 4.8 months, respectively; P = 0.015). There was also significant difference in mortality rates and median overall survival between the study groups (30% in responders vs. 70% in nonresponders at a median time of 27.3 vs. 11.6 months respectively; P = 0.037). Two of the three patients that died in the normalized tumor marker group had tumor marker relapse at recurrence prior to their death. CONCLUSIONS: To our knowledge, this is the first study showing tumor marker response to NAC. Patients with persistently elevated markers following NAC have a very poor prognosis following cystectomy, which may help identifying chemotherapy-resistant tumors. A larger, controlled study with longer follow up is needed to determine their role in predicting survival.

Frailty as a predictor of complications after radical cystectomy: A prospective study of various preoperative assessments.

PURPOSE: Frailty has been correlated with worse postoperative outcomes. Prospective studies examining frailty and bladder cancer are lacking. We aimed to determine whether a prospective frailty assessment or traditional risk indices can identify patients undergoing radical cystectomy (RC) at risk for complications. MATERIALS AND METHODS: Patients ≥65 years undergoing RC were preoperatively assessed using Fried Frailty Criteria (FFC; grip strength, gait speed, exhaustion, physical activity, shrinking), Charlson Comorbidity Index, American Society of Anesthesiologists score, Katz Index of Independence in Activities of Daily Living, Karnofsky Performance Scale, Eastern Cooperative Oncology Group performance status, and Center for Epidemiological Studies Depression scale. Thirty-day and 90-day postoperative complications were recorded. Univariate and multivariate analyses were performed. RESULTS: One hundred and twenty three patients were assessed with median age of 74 years. Fifty-nine patients (48.0%) had ≥1 complication within 30 days and 72 (58.5%) within 90 days. Center for Epidemiological Studies Depression scale (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01-1.17, P = 0.027) and shrinking (OR 3.79, 95% CI 1.64-9.26, P = 0.0024) were significant for any 30-day complication, while physical activity was protective (OR 0.84, 95% CI 0.69-1.00, P = 0.072) for any 90-day complication. Being intermediately frail or frail was associated with high-grade 30-day (OR 4.87, 95% CI 1.39-22.77, P = 0.022) and 90-day complications (OR 3.01, 95% CI 1.05-9.37, P = 0.045), along with Eastern Cooperative Oncology Group score ≥3 (OR 45.00, 95% CI 6.92-437.69, P = 0.0010 and OR 17.85, 95% CI 3.21-143.26, P = 0.0079, respectively). CONCLUSIONS: Fried Frailty Criteria were predictive of high-grade complications, while individual components were predictive of having any complication. Elderly patients should be routinely assessed prior to RC to guide postoperative care.

Urinary tract infections following radical cystectomy and urinary diversion: a review of 1133 patients.

OBJECTIVE: To investigate the incidence and microbiology of urinary tract infection (UTI) within 90 days following radical cystectomy (RC) and urinary diversion. METHODS: We reviewed 1133 patients who underwent RC for bladder cancer at our institution between 2003 and 2013; 815 patients (72%) underwent orthotopic diversion, 274 (24%) ileal conduit, and 44 (4%) continent cutaneous diversion. 90-day postoperative UTI incidence, culture results, antibiotic sensitivity/resistance and treatment were recorded through retrospective review. Fisher's exact test, Kruskal-Wallis test, and multivariable analysis were performed. RESULTS: A total of 151 urinary tract infections were recorded in 123 patients (11%) during the first 90 days postoperatively. 21/123 (17%) had multiple infections and 25 (20%) had urosepsis in this time span. Gram-negative rods were the most common etiology (54% of positive cultures). 52% of UTI episodes led to readmission. There was no significant difference in UTI rate, etiologic microbiology (Gram-negative rods, Gram-positive cocci, fungi), or antibiotic sensitivity and resistance patterns between diversion groups. Resistance to quinolones was evident in 87.5% of Gram-positive and 35% of Gram-negative bacteria. In multivariable analysis, Charlson Comorbidity Index > 2 was associated with higher 90-day UTI rate (OR = 1.8, 95% CI 1.1-2.9, p = 0.05) and Candida UTI (OR 5.6, 95% CI 1.6-26.5, p = 0.04). CONCLUSIONS: UTI is a common complication and cause of readmission following radical cystectomy and urinary diversion. These infections are commonly caused by Gram-negative rods. High comorbidity index is an independent risk factor for postoperative UTI, but diversion type is not.

Satisfaction With Testicular Prosthesis After Radical Orchiectomy.

OBJECTIVES: To determine patient satisfaction with testicular prostheses (TP) for testicular cancer. Reconstruction represents an important part of surgical oncology, yet placement of TP following orchiectomy is infrequently performed. Improved data on patient satisfaction with TP would help in counseling patients with testicular cancer. MATERIALS AND METHODS: Forty patients who underwent orchiectomy and TP placement for testicular cancer participated in a survey that was blinded to the providers in an outpatient clinic (2012-2014) to evaluate TP satisfaction. Categorical variables associated with satisfaction were compared using the Fisher's exact test. RESULTS: Median age at TP placement was 31 years (17-59). Most patients had their prosthesis in place for >1 year (81%) at the time of the survey. No patient reported complications from the TP and none underwent explantation. All patients felt that being offered an implant before orchiectomy was important. Overall, 33 patients (82.5%) rated the TP as good or excellent, and 35 men (87.5%) would have the prosthesis implanted again. Thirty-seven patients (92.5%) found the TP to be comfortable or very comfortable. However, 44% considered the TP too firm and 20% felt the position was not appropriate. Appropriate size, appropriate position, and TP comfort were significantly associated with good or excellent overall TP satisfaction (P < .05). CONCLUSION: Overall satisfaction with testicular implants after orchiectomy for testicular cancer is high. Patients should be offered a testicular prosthesis, especially at the time of orchiectomy. Efforts should be made to optimize implant firmness, and care should be given to proper size selection and positioning.

Impact of body mass index on robot-assisted radical cystectomy with intracorporeal urinary diversion.

OBJECTIVES: To determine the impact of body mass index (BMI) on peri-operative and oncological outcomes after robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion. PATIENTS AND METHODS: A total of 216 patients undergoing RARC, extended lymphadenectomy and intracorporeal urinary diversion, between July 2010 and December 2015, were categorized into four BMI groups according to the 2004 World Health Organization obesity classification groups: <25 kg/m2 (normal); 25-29.9 kg/m2 (pre-obese); 30-34.9 kg/m2 (obese class I); and ≥35 kg/m2 (obese class II). Pre-, intra- and postoperative characteristics, oncological outcomes, and 90-day complications were compared using sas statistical software. RESULTS: All 216 patients underwent intracorporeal urinary diversion, with 68 (32%) undergoing orthotopic neobladder construction. Demographics were similar among the BMI groups with regard to median (range) age (71.8 [35- 95] years), gender (80.6% men), Charlson comorbidity index (CCI) score (66.2% with CCI score 0-1), pathological stage (carcinoma in situ to T2: 55.1%, T3-T4/N0: 18.5%, Tx/N+: 26.4%), median (interquartile range) node count [41 (28, 53)] and positive soft tissue margin rate (4.2%). Obese patients had greater blood loss and longer operating time (P = 0.02 and P = 0.04, respectively). There were no significant differences in length of hospital stay, transfusion rates, readmission or 90-day overall and high-grade complication rates (P = 0.16, P = 0.96, P = 0.89, P = 0.22 and P = 0.51, respectively). At a median (range) follow-up of 13 months (15 days to 4.8 years), recurrence-free survival (P = 0.92) and overall survival (P = 0.68) were similar among the groups. CONCLUSION: The results of the present study show that RARC with intracorporeal urinary diversion is safe and feasible in obese patients with bladder cancer. BMI was not associated with significant differences in peri-operative, pathological or early oncological outcomes.

Midline Extraperitoneal Approach to Retroperitoneal Lymph Node Dissection in Testicular Cancer: Minimizing Surgical Morbidity.

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant surgical morbidity. OBJECTIVE: To describe our experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT. DESIGN, SETTING, AND PARTICIPANTS: From 2010 to 2015, 122 consecutive patients underwent RPLND from a prospective database. Patients requiring aortic resection or retrocrural dissection or with intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. SURGICAL PROCEDURE: Open midline EP-RPLND was performed using a standardized technique. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative and long-term outcomes were analyzed. Complications were graded using the Clavien-Dindo classification. A descriptive analysis using SAS software was performed. RESULTS AND LIMITATIONS: A total of 68 patients underwent midline EP-RPLND successfully (98.6%). The median age was 28 yr (range 17-55). On preoperative imaging the size of the retroperitoneal mass or lymphadenopathy was <2cm in 29 patients, 2-4.9cm in 15 patients, and >5cm in 24 patients, of which 19 were >10cm. The median estimated blood loss was 325ml (interquartile range [IQR] 200-612.5). The median number of lymph nodes resected was 36 (IQR 24.5-49); the median number of positive nodes was one (IQR 0-4). The median time for return of bowel function was 2 d (IQR 1-2) and hospital stay 3 d (IQR 3-4). There were no cases of ileus. Eleven patients had 12 (17.6%) 90-d complications. Of these, six (55%) were Clavien grade 1, five (45%) were grade 2, and one was grade 3b (1.5%). Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the post-chemotherapy group. CONCLUSIONS: Midline EP-RPLND can be performed safely without compromising the completeness of the resection. This approach is associated with rapid return of bowel function, minimal rates of ileus, and short hospital stay. PATIENT SUMMARY: A midline extraperitoneal approach for retroperitoneal lymph node dissection in testicular cancer is safe and effective and leads to faster return of bowel function and earlier discharge.

Structured learning for robotic surgery utilizing a proficiency score: a pilot study.

PURPOSE: We evaluated feasibility and benefit of implementing structured learning in a robotics program. Furthermore, we assessed validity of a proficiency assessment tool for stepwise graduation. METHODS: Teaching cases included robotic radical prostatectomy and partial nephrectomy. Procedure steps were categorized: basic, intermediate, and advanced. An assessment tool ["proficiency score" (PS)] was developed to evaluate ability to safely and autonomously complete a step. Graduation required a passing PS (PS ≥ 3) on three consecutive attempts. PS and validated global evaluative assessment of robotic skills (GEARS) were evaluated for completed steps. Linear regression was utilized to determine postgraduate year/PS relationship (construct validity). Spearman's rank correlation coefficient measured correlation between PS and GEARS evaluations (concurrent validity). Intraclass correlation (ICC) evaluated PS agreement between evaluator classes. RESULTS: Twenty-one robotic trainees participated within the pilot program, completing a median of 14 (2-69) cases each. Twenty-three study evaluators scored 14 (1-60) cases. Over 4 months, 229/294 (78 %) cases were designated "teaching" cases. Residents completed 91 % of possible evaluations; faculty completed 78 %. Verbal and quantitative feedback received by trainees increased significantly (p = 0.002, p < 0.001, respectively). Average PS increased with PGY (post-graduate year) for basic and intermediate steps (regression slopes: 0.402 (p < 0.0001), 0.323 (p < 0.0001), respectively) (construct validation). Overall, PS correlated highly with GEARS (ρ = 0.81, p < 0.0001) (concurrent validity). ICC was 0.77 (95 % CI 0.61-0.88) for resident evaluations. CONCLUSION: Structured learning can be implemented in an academic robotic program with high levels of trainee and evaluator participation, encouraging both quantitative and verbal feedback. A proficiency assessment tool developed for step-specific proficiency has construct and concurrent validity.

Prospective Evaluation of Continence Following Radical Cystectomy and Orthotopic Urinary Diversion Using a Validated Questionnaire.

PURPOSE: We evaluated continence outcomes in male patients undergoing orthotopic neobladder diversion after radical cystectomy using a validated questionnaire. MATERIALS AND METHODS: Using our institutional review board approved bladder cancer database we identified 1,269 patients who underwent open radical cystectomy from 2002 to 2015. Orthotopic neobladder was constructed in 935 (74%) patients, of whom 798 (85%) were male. Beginning in 2012 the patients completed a validated pictorial pad use questionnaire at each followup visit. The questionnaire assessed pad number, size and wetness as well as catheter use. Continence was defined as use of no pads or pads that are almost dry. Questionnaires were stratified into distinct postoperative intervals for analysis. Female patients, or patients with artificial urinary sphincters or prior radiotherapy were excluded from the study. RESULTS: A total of 188 male patients with available questionnaires were followed from September 2012 to August 2015. Overall 447 questionnaires were collected, with 351 interval distinct questionnaires separated into intervals of less than 3, 3 to 6, more than 6 to 12, more than 12 to 18, more than 18 to 36 and more than 36 months after surgery (64, 61, 58, 49, 61 and 58 questionnaires, respectively). Daytime continence increased from 59% at less than 3 months postoperatively to 92% by more than 12 to 18 months. Nighttime continence increased from 28% at less than 3 months postoperatively to 51% by more than 18 to 36 months. Nearly 50% of patients reported daytime and nighttime continence by 18 to 36 months. CONCLUSIONS: After orthotopic neobladder diversion in male patients, continence improves significantly by 6 months and subsequently plateaus with 92% daytime continence by more than 12 to 18 months. Orthotopic neobladder represents an excellent functional option for urinary diversion.

Fyn knock-down increases Aß, decreases phospho-tau, and worsens spatial learning in 3×Tg-AD mice.

Fyn kinase phosphorylates tau and exacerbates amyloid beta (Aß)-mediated synaptic dysfunction. However, Fyn also increases the nonpathological cleavage of amyloid precursor protein (APP), suggesting opposing roles for Fyn in the pathogenesis of Alzheimer's disease (AD). To determine the effect of Fyn on both Aß and tau pathologies, we crossed homozygous Alzheimer's disease triple transgenic (3×Tg) mice harboring mutations in amyloid precursor protein, presenilin-1, and tau with wild-type or Fyn knockout mice to generate Fyn(+/+)3×Tg(+/-) or Fyn(+/-)3×Tg(+/-) mice. We found that Fyn(+/-)3×Tg(+/-) mice had increased soluble and intracellular Aß, and these changes were accompanied by impaired performance on the Morris water maze at 18 months. Fyn(+/-)3×Tg(+/-) mice had decreased phosphorylated tau at 15-18 months (as did Fyn knockout mice), but Fyn(+/-)3×Tg(+/-) mice had increased phosphorylated tau by 24 months. In addition, we observed that Fyn(+/-)3×Tg(+/-) males were delayed in developing Aß pathology compared with females, and displayed better spatial learning performance at 18 months. Overall, these findings suggest that loss of Fyn at early stages of disease increases soluble Aß accumulation and worsens spatial learning in the absence of changes in tau phosphorylation.