Mielke, Michelle M.

BACKGROUND: We evaluated the hypothesis that the rate of postoperative decline in global cognition is greater in older adults exposed to general anesthesia with nitrous oxide (N 2 O) compared to general anesthesia without N 2 O. METHODS: Longitudinal measures of cognitive function were analyzed in nondemented adults, 70–91 years of age, enrolled in the Mayo Clinic Study of Aging. Linear mixed-effects models with time-varying covariates assessed the relationship between exposure to surgery with general anesthesia (surgery/GA) with or without N 2 O and the rate of long-term cognitive changes. Global cognition and domain-specific cognitive outcomes were defined using z scores, which measure how far an observation is, in standard deviations, from the unimpaired population mean. RESULTS: The analysis included 1819 participants: 280 exposed to GA without N 2 O following enrollment and before censoring during follow-up (median [interquartile range {IQR}] follow-up of 5.4 [3.9–7.9] years); 256 exposed to GA with N 2 O (follow-up 5.6 [4.0–7.9] years); and 1283 not exposed to surgery/GA (follow-up 4.1 [2.5–6.4] years). The slope of the global cognitive z score was significantly more negative following exposure to surgery/GA after enrollment (change in slope of −0.062 [95% confidence interval {CI}, −0.085 to −0.039] for GA without N 2 O, and −0.058 [95% CI, −0.080 to −0.035] for GA with N 2 O, both P < .001). The change in slope following exposure to surgery/GA did not differ between those exposed to anesthesia without versus with N 2 O (estimated difference −0.004 [95% CI, −0.035 to 0.026], P = .783). CONCLUSIONS: Exposure to surgery/GA is associated with a small, but statistically significant decline in cognitive z scores. Cognitive decline did not differ between anesthetics with and without N 2 O. This finding provides evidence that the use of N 2 O in older adults does not need to be avoided because of concerns related to decline in cognition.

Abstract Introduction Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total‐tau [T‐tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging–Alzheimer's Association Research Framework. Methods We examined, in a community‐based population (N = 777, aged 50–95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T‐tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in‐house enzyme‐linked immunosorbent assays. Results Multiple variables were differentially associated with CSF NfL and T‐tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T‐tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status. Discussion Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.

AbstractIntroductionPractical algorithms predicting the probability of amyloid pathology among patients with subjective cognitive decline or mild cognitive impairment may help clinical decisions regarding confirmatory biomarker testing for Alzheimer's disease.MethodsAlgorithm feature selection was conducted with Alzheimer's Disease Neuroimaging Initiative and Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing data. Probability algorithms were developed in Alzheimer's Disease Neuroimaging Initiative using nested cross‐validation accompanied by stratified subsampling to obtain 1000 internally validated decision trees. Semi‐independent validation was conducted using Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Independent external validation was conducted in the population‐based Mayo Clinic Study of Aging.ResultsTwo algorithms were developed using age and normalized immediate recall z‐scores, with or without apolipoprotein E ε4 carrier status. Both algorithms had robust performance across data sets and when substituting different recall memory tests.DiscussionThe statistical framework resulted in robust probability estimation. Application of these algorithms may assist in clinical decision‐making for further testing to diagnose amyloid pathology.