Clinton E. Hagen

Detection of Recurrent Prostate Cancer After Radical Prostatectomy: Comparison of 11C-Choline PET/CT with Pelvic Multiparametric MR Imaging with Endorectal Coil

The aim of this study was to compare 11C-choline PET/CT with pelvic multiparametric MR imaging for detection of recurrent prostate carcinoma in patients with suspected recurrence after radical prostatectomy and to identify an optimal imaging method to restage these patients. Methods: This was a retrospective, single-institution study of 115 prostatectomy patients with suspected tumor recurrence who underwent both 11C-choline PET/CT and multiparametric MR imaging with endorectal coil. The reference standard included histopathology, treatment change, and imaging follow-up for determination of locally recurrent tumor, lymph node (LN) metastases, and skeletal metastases. Two nuclear medicine and 2 genitourinary radiologists independently and in a masked manner reviewed PET/CT and multiparametric MR imaging, respectively. The reviewers assessed for local recurrence in the prostatectomy bed as well as LN and bone metastases, rating their diagnostic confidence with a 5-point scoring system for each location. Receiver-operating-characteristic analysis was used to compare the 2 modalities. Results: The standard of reference (either positive or negative) for the diagnosis of local recurrence and pelvic LN and bone metastases was met in 87, 70, and 95 patients, respectively. Documented local recurrence and pelvic LN and bone metastases was present in 61 of 87 (70.1%), 50 of 70 (71.4%), and 16 of 95 (16.8%) patients, respectively. Patient-based area under the receiver-operating-characteristic curves of multiparametric MR imaging versus PET/CT for the diagnosis of local recurrence and pelvic LN and bone metastases were 0.909 versus 0.761 (P = 0.0079), 0.812 versus 0.952 (P = 0.0064), and 0.927 versus 0.898 (P = 0.69), respectively. Among 61 patients with local recurrence, 32 patients (52.4%) were correctly diagnosed as having local recurrence by both multiparametric MR imaging and PET/CT, 22 (36.1%) were correctly diagnosed by multiparametric MR imaging only, 6 (9.8%) could not be diagnosed by either modality, and 1 (1.6%) was correctly diagnosed by PET/CT only. The patient-based sensitivity, specificity, and accuracy of multiparametric MR imaging for diagnosing local recurrence were 88.5% (54/61), 84.6% (22/26), and 87.4% (76/87) whereas those of PET/CT for detecting body LN or bone metastases were 92.3% (72/78), 100% (18/18), and 93.8% (90/96), respectively. Conclusion: Multiparametric MR imaging with endorectal coil is superior for the detection of local recurrence, PET/CT is superior for pelvic LN metastasis, and both were equally excellent for pelvic bone metastasis. 11C-choline PET/CT and pelvic multiparametric MR imaging are complementary for restaging prostatectomy patients with suspected recurrent disease.

Idiopathic subglottic stenosis: an evolving therapeutic algorithm.

Idiopathic subglottic stenosis (ISS) is a rare type of airway stenosis of unclear etiology. Open resection, while effective, remains a complex surgery and requires a hospital stay. Endoscopic management is often preferred but has historically been associated with a high recurrence rate. We aimed to analyze our experience, consisting of a standardized endoscopic approach combined with an empiric medical treatment.

Detection of Local Recurrence of Prostate Cancer After Radical Prostatectomy Using Endorectal Coil MRI at 3 T: Addition of DWI and Dynamic Contrast Enhancement to T2-Weighted MRI

OBJECTIVE The purpose of this study was to assess the utility of DWI and dynamic contrast enhancement (DCE) in MRI at 3 T with an endorectal coil in identifying local prostate cancer recurrence after radical prostatectomy. MATERIALS AND METHODS Eighty men underwent MRI for suspected local recurrence. The reference standards were histopathologic result, decrease in prostate-specific antigen level after salvage radiation therapy, and follow-up findings. Using a 5-point scoring system, two reviewers independently interpreted T2-weighted images alone (protocol A), a combination of T2-weighted and DW images (protocol B), a combination of T2-weighted and DCE images (protocol C), and a combination of T2-weighted, DW, and DCE images (protocol D). ROC analysis was used to compare the four protocols. RESULTS Local recurrence was found in 57 of the 80 patients (71.3%). The ROC AUCs for protocols A, B, C, and D were 0.71, 0.72, 0.90, and 0.89 for reader 1 and 0.65, 0.62, 0.84, and 0.83 for reader 2. Protocols C and D had statistically better performance than protocols A and B for both readers (p < 0.001). For local recurrence lesions with a long-axis diameter less than 10 mm visualized with protocol C, protocol B had detection rates of 25.0-29.4% and for lesions measuring 10 mm or greater, 67.9-69.0%. The rates of detection of local recurrence with protocol C or D were 76.5-82.4% for prostate-specific antigen levels less than 0.4 ng/mL, 60-73.3% for 0.4-1.0 ng/mL, and 80-88.0% for greater than 1.0 ng/mL. CONCLUSION Addition of DCE to T2-weighted imaging in 3-T MRI with an endorectal coil improves the accuracy of detection of local cancer recurrence after radical prostatectomy. The addition of DWI is of limited incremental value for detection, especially of small lesions.

LEVELS OF TAU PROTEIN IN PLASMA ARE ASSOCIATED WITH NEURODEGENERATION AND COGNITIVE FUNCTION IN A POPULATION-BASED ELDERLY COHORT

Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimers disease (AD)–related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals.

Comparison of Gait Parameters for Predicting Cognitive Decline: The Mayo Clinic Study of Aging

BACKGROUND Previous studies reported that slower gait speed might predict cognitive impairment and dementing illnesses, supporting the role of gait speed as a possible subclinical marker of cognitive impairment. However, the predictive value of other gait parameters for cognitive decline is unclear. OBJECTIVE To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample. METHODS The analysis included 3,426 cognitively normal participants enrolled in the Mayo Clinic Study of Aging. At baseline and every 15 months (mean follow-up = 1.93 years), participants had a study coordinator evaluation, neurological examination, and a neuropsychological assessment using nine tests that covered four domains. Gait parameters were assessed with the GAITRite® instrument. General linear mixed effects models were used to compute the annualized rate of change in cognitive domain z-scores, controlling for age, sex, education, depression, comorbidities, body mass index, APOE ɛ4 allele, and visit number, and excluding individuals with a history of stroke, alcoholism, Parkinsons disease, subdural hematoma, and normal pressure hydrocephalus. RESULTS Spatial (stride length), temporal (ambulatory time, gait speed, step count, cadence, double support time), and spatiotemporal (cadence) gait parameters, and greater intraindividual variability in stride length, swing time, and stance time were associated with a significant decline in global cognition and in specific domains including memory, executive function, visuospatial, and language. CONCLUSIONS Spatial, temporal, and spatiotemporal measures of gait and greater variability of gait parameters were associated with and predictive of both global- and domain-specific cognitive decline.

Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging.

To determine the cross‐sectional association between cerebral amyloid‐beta (Aβ) deposition and gait.

Influence of amyloid and APOE on cognitive performance in a late middle-aged cohort

Few studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle‐aged individuals.

Performance of the CogState computerized battery in the Mayo Clinic Study on Aging

The feasibility and validity of brief computerized cognitive batteries at the population‐level are unknown.

Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging

Importance The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood. Objectives To determine (1) the association between plasma total tau level, cognitive decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid &bgr; (A&bgr;); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months. Design, Setting, and Participants The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013. All included participants had available plasma total tau levels, A&bgr; positron emission tomography imaging, and a complete neuropsychological examine at the same visit, as well as at least 1 follow-up visit. Exposures Concentration of plasma total tau. Main Outcomes and Measures Risk of MCI and dementia; global and domain-specific cognitive decline. Results Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6) years. Among cognitively normal (CN) participants oversampled for elevated brain A&bgr;, both the middle (hazard ratio [HR], 2.43; 95% CI, 1.25-4.72) and highest (HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with the lowest, were associated with an increased risk of MCI. Among participants with MCI, higher plasma total tau levels were not significantly associated with risk of dementia (all-cause dementia or Alzheimer disease). Among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant (P < .05) declines in global cognition, memory, attention, and visuospatial ability over a median follow-up of 3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow-up to 15 months, plasma total tau did not predict decline among CN participants. However, among participants with MCI, higher plasma total tau levels were associated with greater decline in both visuospatial ability (regression coefficient [b] = −0.50 [0.15], P < .001) and global cognition (b = −0.27 [0.10], P = .009) at 15 months. Adjusting for elevated brain A&bgr; did not attenuate any association. There was no interaction between plasma total tau level and brain A&bgr; for prognosis with any outcome. Conclusions and Relevance These results suggest that elevated plasma total tau levels are associated with cognitive decline, but the results differ based on cognitive status and the duration of follow-up. The association between plasma total tau levels and cognition is independent of elevated brain A&bgr;.

Serum Adiponectin Levels, Neuroimaging, and Cognition in the Mayo Clinic Study of Aging

BACKGROUND Adiponectin, a protein involved in inflammatory pathways, may impact the development and progression of Alzheimers disease (AD). Adiponectin levels have been associated with mild cognitive impairment (MCI) and AD; however, its association with Alzheimer-associated neuroimaging and cognitive outcomes is unknown. OBJECTIVE Determine the cross-sectional association between plasma adiponectin and neuroimaging and cognitive outcomes in an older population-based sample. METHODS Multivariable adjusted regression models were used to investigate the association between plasma adiponectin and hippocampal volume (HVa), PiB-PET, FDG PET, cortical thickness, MCI diagnosis, and neuropsychological test performance. Analyses included 535 non-demented participants aged 70 and older enrolled in the Mayo Clinic Study of Aging. RESULTS Women had higher adiponectin than men (12,631 ng/mL versus 8,908 ng/mL, p < 0.001). Among women, higher adiponectin was associated with smaller HVa (B = -0.595; 95% CI -1.19, -0.005), poorer performance in language (B = -0.676; 95% CI -1.23, -0.121), and global cognition (B = -0.459; 95% CI -0.915, -0.002), and greater odds of a MCI diagnosis (OR = 6.23; 95% CI 1.20, 32.43). In analyses stratified by sex and elevated amyloid (PiB-PET SUVR >1.4), among women with elevated amyloid, higher adiponectin was associated with smaller HVa (B = -0.723; 95% CI -1.43, -0.014), poorer performance in memory (B = -1.02; 95% CI -1.73, -0.312), language (B = -0.896; 95% CI -1.58, -0.212), global cognition (B = -0.650; 95% CI -1.18, -0.116), and greater odds of MCI (OR = 19.34; 95% CI 2.72, 137.34). CONCLUSION Higher plasma adiponectin was associated with neuroimaging and cognitive outcomes among women. Longitudinal analyses are necessary to determine whether higher adiponectin predicts neurodegeneration and cognitive decline.