Distribution and predictive value of all self-perceived SCD and iSCD measures for incident MCI in the MCSA

Table 1: Distribution and predictive value of SCD scores. Table 2: Distribution and predictive value of iSCD scores

In-Hospital Versus Out-of-Hospital Stroke Onset Comparison of Process Metrics in a Community Primary Stroke Center

Objective: To examine in-hospital stroke onset metrics and outcomes, quality of care, and mortality compared with out-of-hospital stroke in a single community-based primary stroke center. Patients and Methods: Medical records of in-hospital stroke onset were compared with out-of-hospital stroke onset alert data between January 1, 2013 and December 31, 2019. Time-sensitive stroke process metric data were collected for each incident stroke alert. The primary focus of interest was the time-sensitive stroke quality metrics. Secondary focus pertained to thrombolysis treatment or complications, and mortality. Descriptive and univariable statistical analyses were applied. Kruskal-Wallis and χ2 tests were used to compare median values and categorical data between prespecified groups. The statistical significance was set at α=0.05. Results: The out-of-hospital group reported a more favorable response to time-sensitive stroke process metrics than the in-hospital group, as measured by median stroke team response time (15.0 vs 26.0 minutes; P≤.0001) and median head computed tomography scan completion time (12.0 vs 41.0 minutes; P=.0001). There was no difference in the stroke alert time between the 2 groups (14.0 vs 8.0 minutes; P=.089). Longer hospital length of stay (4 vs 3 days; P=.004) and increased hospital mortality (19.3% vs 7.4%; P=.0032) were observed for the in-hospital group. Conclusions: The key findings in this study were that time-sensitive stroke process metrics and stroke outcome measures were superior for the out-of-hospital groups compared with the in-hospital groups. Focusing on improving time-sensitive stroke process metrics may improve outcomes in the in-hospital stroke cohort

Subjective cognitive decline and risk of MCI: The Mayo Clinic Study of Aging

© 2018 American Academy of Neurology. OBJECTIVE: We investigated different dimensions of subjective cognitive decline (SCD) to determine which was the best prognostic risk factor for incident mild cognitive impairment (MCI) among cognitively unimpaired participants. METHODS: We included 1,167 cognitively unimpaired participants, aged 70 to 95 years, from the Mayo Clinic Study of Aging based on 2 concurrent SCD scales (part of the Blessed memory test and the 39-item Everyday Cognition [ECog] scale, which included a validated 12-item derivative) and a single question assessing worry about cognitive decline. We evaluated multiple ways to dichotomize scores. In continuous models, we compared average scores on 4 ECog domains and multidomain (39- and 12-item) ECog scores. Cox proportional hazards models were used to assess the association between each measure and risk of MCI in models adjusted for objective memory performance, depression, anxiety, sex, APOE ε4 carriership, and medical comorbidities. RESULTS: It was possible to select a substantial group of participants (14%) at increased risk of incident MCI based on combined baseline endorsement of any consistent SCD on the ECog (any item scored ≥3; 12-item ECog hazard ratio [HR] 2.17 [95% confidence interval 1.51-3.13]) and worry (HR 1.79 [1.24-2.58]) in an adjusted model combining these dimensions. In continuous models, all ECog domains and the multidomain scores were associated with risk of MCI with a small advantage for multidomain SCD (12-item ECog HR 2.13 [1.36-3.35] per point increase in average score). Information provided by the informant performed comparable to self-perceived SCD. CONCLUSION: Prognostic value of SCD for incident MCI improves when both consistency of SCD and associated worry are evaluated

Subjective cognitive decline and risk of MCI: The Mayo Clinic Study of Aging

© 2018 American Academy of Neurology. OBJECTIVE: We investigated different dimensions of subjective cognitive decline (SCD) to determine which was the best prognostic risk factor for incident mild cognitive impairment (MCI) among cognitively unimpaired participants. METHODS: We included 1,167 cognitively unimpaired participants, aged 70 to 95 years, from the Mayo Clinic Study of Aging based on 2 concurrent SCD scales (part of the Blessed memory test and the 39-item Everyday Cognition [ECog] scale, which included a validated 12-item derivative) and a single question assessing worry about cognitive decline. We evaluated multiple ways to dichotomize scores. In continuous models, we compared average scores on 4 ECog domains and multidomain (39- and 12-item) ECog scores. Cox proportional hazards models were used to assess the association between each measure and risk of MCI in models adjusted for objective memory performance, depression, anxiety, sex, APOE ε4 carriership, and medical comorbidities. RESULTS: It was possible to select a substantial group of participants (14%) at increased risk of incident MCI based on combined baseline endorsement of any consistent SCD on the ECog (any item scored ≥3; 12-item ECog hazard ratio [HR] 2.17 [95% confidence interval 1.51-3.13]) and worry (HR 1.79 [1.24-2.58]) in an adjusted model combining these dimensions. In continuous models, all ECog domains and the multidomain scores were associated with risk of MCI with a small advantage for multidomain SCD (12-item ECog HR 2.13 [1.36-3.35] per point increase in average score). Information provided by the informant performed comparable to self-perceived SCD. CONCLUSION: Prognostic value of SCD for incident MCI improves when both consistency of SCD and associated worry are evaluated

Synthesis and Preliminary Evaluation of <i>N</i>‑(16‑¹⁸F-Fluorohexadecanoyl)ethanolamine (¹⁸F‑FHEA) as a PET Probe of <i>N</i>‑Acylethanolamine Metabolism in Mouse Brain

<i>N</i>-Acylethanolamines are lipid signaling molecules found throughout the plant and animal kingdoms. The best-known mammalian compound of this class is anandamide, <i>N</i>-arachidonoylethanolamine, one of the endogenous ligands of cannabinoid CB1 and CB2 receptors. Signaling by <i>N</i>-acylethanolamines is terminated by release of the ethanolamine moiety by hydrolyzing enzymes such as fatty acid amide hydrolase (FAAH) and <i>N</i>-acylethanolamine-hydrolyzing amidase (NAAA). Herein, we report the design and synthesis of <i>N</i>-(16-¹⁸F-fluorohexadecanoyl)­ethanolamine (¹⁸F-FHEA) as a positron emission tomography (PET) probe for imaging the activity of <i>N</i>-acylethanolamine hydrolyzing enzymes in the brain. Following intravenous administration of ¹⁸F-FHEA in Swiss Webster mice, ¹⁸F-FHEA was extracted from blood by the brain and underwent hydrolysis at the amide bond and incorporation of the resultant ¹⁸F-fluorofatty acid into complex lipid pools. Pretreatment of mice with the FAAH inhibitor URB-597 (1 mg/kg IP) resulted in significantly slower ¹⁸F-FHEA incorporation into lipid pools, but overall ¹⁸F concentrations in brain regions were not altered. Likewise, pretreatment with a NAAA inhibitor, (<i>S</i>)-<i>N</i>-(2-oxo-3-oxytanyl)­biphenyl-4-carboxamide (30 mg/kg IV), did not significantly affect the uptake of ¹⁸F-FHEA in the brain. Although evidence was found that ¹⁸F-FHEA behaves as a substrate of FAAH in the brain, the lack of sensitivity of brain uptake kinetics to FAAH inhibition discourages its use as a metabolically trapped PET probe of <i>N</i>-acylethanolamine hydrolyzing enzyme activity

Association of Cerebrospinal Fluid Neurofilament Light Protein with Risk of Mild Cognitive Impairment among Individuals Without Cognitive Impairment

Importance: Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau). Objective: To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations. Design, Setting and Participants: The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid. Main Outcomes and Measures: Risk of MCI. Results: At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI. Conclusions and Relevance: Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid