Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ.

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Prognostic value of SCD for incident MCI improves when both consistency of SCD and associated worry are evaluated.

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 β (Aβ); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months. DESIGN, SETTING, AND PARTICIPANTSThe 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, Aβ 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. RESULTSOf 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 Aβ, 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 Aβ did not attenuate any association. There was no interaction between plasma total tau level and brain Aβ for prognosis with any outcome. CONCLUSIONS AND RELEVANCEThese 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 Aβ.

The aim of this study was to compare 11 C-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 11 C-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-operatingcharacteristic 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-operatingcharacteristic 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 5 0.0079), 0.812 versus 0.952 (P 5 0.0064), and 0.927 versus 0.898 (P 5 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. 11 C-choline PET/CT and pelvic multiparametric MR imaging are complementary for restaging prostatectomy patients with suspected recurrent disease.

INTRODUCTION Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimer's Disease (AD)-related MRI and PET neuroimaging measures among non-demented individuals. METHODS Participants included 378 cognitively normal (CN) and 161 Mild Cognitive Impairment (MCI) individuals enrolled in the Mayo Clinic Study of Aging with concurrent neuropsychological measures and amyloid PET, FDG-PET, and MRI imaging. Baseline plasma tau levels were measured using the Quanterix Simoa-HD1 tau assay. RESULTS Plasma tau levels were higher in MCI compared to CN (4.34 vs. 4.14 pg/mL, P=0.078). In regression models adjusted for age, sex, education, and APOE, higher plasma tau was associated with worse memory performance (b=−0.30, P=0.02) and abnormal cortical thickness in an AD signature region (OR=1.80, P=0.018). DISCUSSION Plasma tau is associated with cortical thickness and memory performance. Longitudinal studies will better elucidate the associations between plasma tau, neurodegeneration, and cognition.

Background The feasibility and validity of brief computerized cognitive batteries at the population-level are unknown. Methods Non-demented participants (n = 1660, age 50–97) in the Mayo Clinic Study on Aging completed the computerized CogState battery and standard neuropsychological battery. The correlation between tests was examined and comparisons between CogState performance on the personal computer (PC) and iPad (n = 331), and in the Clinic vs. at home (n = 194), were assessed. Results We obtained valid data on >97% of participants on each test. Correlations between the CogState and neuropsychological tests ranged from −0.462 to 0.531. While absolute differences between the PC and iPad were small and participants preferred the iPad, performance on the PC was faster. Participants performed faster on Detection, One Card Learning, and One Back at home compared to the Clinic. Conclusions The computerized CogState battery, especially the iPad, was feasible, acceptable, and valid in the population.

Objective To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample. 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. 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 ε4 allele, and visit number, and excluding individuals with a history of stroke, alcoholism, Parkinson’s 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.