Use of a Shear Reduction Surface for Prehospital Transport: A Randomized Crossover Study.

OBJECTIVE: To compare the effectiveness of an antishear mattress overlay (ASMO) with a standard ambulance stretcher surface in reducing pressure and shear and increasing patient comfort. METHODS: In this randomized, crossover design, adults in three body mass index categories served as their own controls. Pressure/shear sensors were applied to the sacrum, ischial tuberosity, and heel. The stretcher was placed in sequential 0°, 15°, and 30° head-of-bed elevations with and without an ASMO. The ambulance traveled a closed course, achieving 30 mph, with five stops at each head-of-bed elevation. Participants rated discomfort after each series of five runs. RESULTS: Thirty individuals participated. Each participant had 30 runs (15 with an ASMO, 15 without), for a total of 900 trial runs. The peak-to-peak shear difference between support surfaces was -0.03 N, indicating that after adjustment for elevation, sensor location, and body mass index, peak shear levels at baseline (starting pause) were 0.03 N lower for the ASMO than for the standard surface ( P = .02). The peak-to-peak pressure difference between surfaces was -0.16 mm Hg, indicating that prerun peak-to-peak pressure was 0.16 mm Hg lower with the ASMO versus standard surface ( P = .002). The heel received the most pressure and shear. Discomfort score distributions differed between surfaces at 0° ( P = .004) and 30° ( P = .01); the overall score across all elevations was significantly higher with the standard surface than with the ASMO ( P = .046). CONCLUSIONS: The ASMO reduced shear, pressure, and discomfort. During transport, the ambulance team should provide additional heel offloading.

Androgen Deprivation Therapy Use and Risk of Mild Cognitive Impairment in Prostate Cancer Patients.

INTRODUCTION: We examined the association between androgen deprivation therapy (ADT) use and the risk of mild cognitive impairment (MCI) among prostate cancer patients. METHODS: We included 241 cognitively unimpaired men, aged 70 to 90, with a history of prostate cancer before enrollment in the population-based Mayo Clinic Study of Aging. Using the Rochester Epidemiology Project medical records-linkage system, ADT use and length of exposure were abstracted. Follow-up visits occurred every 15 months and MCI diagnoses were made based on clinical consensus. Cox proportional hazards models, with age as the timescale, were used to examine the association between ADT use (yes/no) and length of exposure with the risk of MCI adjusting for education, apolipoprotein E, depression, and the Charlson Index score. RESULTS: There was no association between any ADT use (27.8% of participants) and the risk of MCI in the multivariable model [hazard ratio (HR), 1.25; 95% confidence interval (CI), 0.75-2.10]. Although not significant, there was an ADT dose-response relationship for risk of MCI: <5 years versus no use (HR, 1.08; 95% CI, 0.60-1.96) and ≥5 years versus not use (HR, 1.89; 95% CI, 0.83-4.27). CONCLUSION: ADT use among prostate cancer patients was not associated with an increased risk of developing MCI.

Limited diagnostic impact of duplications <1 Mb of uncertain clinical significance: a 10-year retrospective analysis of reporting practices at the Mayo Clinic.

PURPOSE: Copy-number variants (CNVs) of uncertain clinical significance are routinely reported in a clinical setting only when exceeding predetermined reporting thresholds, typically based on CNV size. Given that very few genes are associated with triplosensitive phenotypes, it is not surprising that many interstitial duplications <1 Mb are found to be inherited and anticipated to be of limited or no clinical significance. METHODS: In an effort to further refine our reporting criteria to maximize diagnostic yield while minimizing the return of uncertain variants, we performed a retrospective analysis of all clinical microarray cases reported in a 10-year window. A total of 1112 reported duplications had parental follow-up, and these were compared by size, RefSeq gene content, and inheritance pattern. De novo origin was used as a rough proxy for pathogenicity. RESULTS: Approximately 6% of duplications 500 kb-1 Mb were de novo observations, compared with approximately 14% for 1-2 Mb duplications (p = 0.0005). On average, de novo duplications had higher gene counts than inherited duplications. CONCLUSION: Our data reveal limited diagnostic utility for duplications of uncertain significance <1 Mb. Considerations for revised reporting criteria are discussed and are applicable to CNVs detected by any genome-wide exploratory methodology, including exome/genome sequencing.

The Cross-sectional and Longitudinal Associations Between IL-6, IL-10, and TNFα and Cognitive Outcomes in the Mayo Clinic Study of Aging.

BACKGROUND: Chronic inflammation has been linked with geriatric-related conditions, including dementia. Inflammatory cytokine levels, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) α, in the blood have been associated with cognitive impairment and decline. However, evidence has been mixed. METHODS: We examined the cross-sectional and longitudinal associations between baseline-measured IL-6, IL-10, and TNFα levels and the ratio of IL-6/IL-10 with cognitive test performance and mild cognitive impairment (MCI) among 1,602 community-dwelling older adults (median age = 72.8) enrolled in the Mayo Clinic Study of Aging. Approximately half (46.5%) of participants were female and 98.6% were white. At baseline and follow-up visits (occurring at 15-month intervals), participants completed neuropsychological testing, blood draws, and had a clinical consensus diagnosis. RESULTS: In multivariable cross-sectional analyses, we did not observe an association between inflammatory cytokine levels and global or domain-specific cognitive z scores; however, higher IL-6 and IL-10 levels were associated with greater odds of a MCI diagnosis. Longitudinally, we did not observe any association between inflammatory cytokine levels and cognitive test performance or risk of MCI. Sex, age, cognitive status, APOE ε4 genotype, diabetes, depression, and cerebral amyloid-beta deposition were not effect modifiers. CONCLUSIONS: These results suggest that plasma inflammatory markers may not be useful to ascertain risk for cognitive decline and MCI in the general population.

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-ß (Aß42) 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 Aß42, 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, Aß42, 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 Aß42 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 Aß42 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.

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

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.

Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging.

OBJECTIVE: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. METHODS: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. RESULTS: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P < .001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P = .009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P = .014) use were also associated with risk of MCI diagnosis. CONCLUSIONS: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

INTRODUCTION: We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid ß (Aß) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aß. METHODS: Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aß PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. RESULTS: Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aß and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aß than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). DISCUSSION: Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aß.

The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging.

Levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, and their ratio in the blood may be useful for monitoring those at risk of cognitive and functional decline. However, the association between IGF measures and functional and cognitive outcomes has been mixed, and the associations may vary by sex. The present study investigated the cross-sectional, sex-specific associations between serum measures total IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio, gait speed, and cognition in 1320 cognitively unimpaired participants aged 50-95 years enrolled in the Mayo Clinic Study of Aging. We used multivariable linear regression models to determine the association between IGF measures and gait speed or cognitive test performance by sex. IGF measures were not associated with cognitive or functional performance among men. Among women, higher levels of log total IGF-1 and IGFBP-3 were associated with better performance in attention, visuospatial, and global cognitive domains, independent of the gait speed. These findings suggest that among women, IGF measures are associated with cognition, and these associations are independent of function.

Trajectories of plasma IGF-1, IGFBP-3, and their ratio in the Mayo Clinic Study of Aging.

Insulin-like growth factor 1 (IGF-1) has been associated with osteoporosis, cardiovascular disease, cancer, neurodegenerative diseases, and mortality in middle and older aged adults. Cross-sectionally, IGF-1 decreases with age and levels of IGF-1 are markedly different between individuals. However, little is known about intra-individual trajectories of IGF-1. We examined baseline and serial measures of plasma total IGF-1, IGF binding protein (IGFBP)-3, and their ratio, which is a proxy for bioavailable IGF-1, among 1618 adults, aged 50-95, enrolled in the Mayo Clinic Study of Aging. At baseline, IGF-1 and IGFBP-3 were strongly correlated (r = 0.62, p < 0.001). Total IGF-1 and IGFBP-3 decreased across age, while the ratio of IGF-1/IGFBP-3 increased across age. This pattern was consistent across ages at baseline and intra-individually over an average 2.3 years follow-up (range = 10 months-5.6 years). In age-adjusted linear regression models, baseline levels of total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 varied by participant characteristics (sex, BMI, gait speed), medical comorbidities (Charlson comorbidity index score, hypertension, diabetes, and cardiovascular disease), and hormone replacement therapy use in women. High interclass correlation coefficients (ICCs) suggest little intra-individual variability in levels of total IGF-1 (ICC = 0.84), IGFBP-3 (ICC = 0.88), and IGF-1/IGFBP-3 (ICC = 0.81) over time. In mixed effects models that specified age as a time scale, men showed greater decreases in total IGF-1 and IGFBP-3 with age, while more comorbidities and decreasing gait speed were associated with increasing IGFBP-3. In sex-stratified models, trajectories of total IGF-1, IGFBP-3, and IGF-1/IGFBP-3, as a function of participant demographics, health characteristics, and medical conditions, differed between men and women. These results suggest that change in levels of plasma total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 are associated with demographics, health characteristics, and medical conditions, and that the trajectories of change differ by sex. Future research should consider how IGF-1 and IGFBP-3 might be useful in research or clinic, paying particular attention to how sex may impact levels as a function of demographics, health characteristics, and medical conditions.

Plasma Sphingolipids are Associated With Gait Parameters in the Mayo Clinic Study of Aging.

Background: Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function. Methods: We examined the cross-sectional association between plasma ceramides, sphingosine-1-phosphate (S1P), and ceramide/S1P ratios and gait, a robust measure of physical function, in 340 clinically normal participants aged 70 years and older enrolled in the Mayo Clinic Study of Aging. GAITRite® instrumentation was used to measure gait speed, cadence, step width, double support time, and intra-individual stride time variability. Based on previous studies, we hypothesized that higher plasma levels of ceramide C16:0 would be associated with worse gait. Results: Multivariable adjusted linear regression models revealed that higher levels of ceramide C16:0 were associated with slower gait speed, decreased cadence, and increased double support time. Conclusions: These results suggest an association between plasma ceramide C16:0 and physical function. Longitudinal studies are needed to determine whether elevated ceramide C16:0 can be utilized as a prognostic marker for functional decline.

Longitudinal Association Between Brain Amyloid-Beta and Gait in the Mayo Clinic Study of Aging.

Background: The longitudinal association between cerebral amyloid-beta (Aß) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined. Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aß, cortical thickness, and gait measurements. Cerebral Aß deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor). Cortical thickness was assessed on 3T MRI in corresponding ROIs. Gait parameters (gait speed, cadence, stride length, double support time, and covariance of stance time) were measured with GAITRite. Multivariate-adjusted two level structural equation models were used to examine the longitudinal association between PiB-PET, cortical thickness, and change in gait over a median 15.6 months. Results: Higher PiB-PET in all ROIs was associated with decreasing cadence and increasing double support time, and in the temporal ROI was associated with declining gait speed. In sex-stratified analyses, higher PiB-PET in all ROIs was associated with declining performance on all gait parameters among women. In contrast, among men, the only association was with higher orbitofrontal ROI PiB-PET and declining cadence. None of the associations were mediated by cortical thickness or attenuated after adjustment of baseline cognition. Conclusion: Higher PiB-PET was associated with declining gait, particularly among women in this middle-aged CN cohort, independent of cortical thickness and baseline cognitive. Elevated brain Aß may play a critical role in age-related mobility decline.

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 ß (Aß); 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, Aß 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 Aß, 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 Aß did not attenuate any association. There was no interaction between plasma total tau level and brain Aß 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 Aß.

The impact of postpartum hemorrhage on hospital length of stay and inpatient mortality: a National Inpatient Sample-based analysis.

BACKGROUND: Postpartum hemorrhage is a major cause of maternal morbidity and mortality, but the association between postpartum hemorrhage and hospital length of stay has not been rigorously investigated. OBJECTIVE: We explored the impact of postpartum hemorrhage on hospital length of stay and inpatient mortality, as these outcomes have both clinical and economic significance. STUDY DESIGN: We performed a retrospective analysis using data from the National Inpatient Sample database during the 2012 through 2013 time period. Deliveries were classified as postpartum hemorrhage due to uterine atony, nonatonic postpartum hemorrhage, or not complicated by postpartum hemorrhage (nonpostpartum hemorrhage). Average length of stay and inpatient mortality rates were compared between groups. RESULTS: Over the study interval, postpartum hemorrhage occurred in 3% of deliveries. Among deliveries complicated by postpartum hemorrhage, 76.6% were attributed to uterine atony and 23.4% were nonatonic. Women with nonatonic postpartum hemorrhage had the highest average length of stay (3.67 days) followed by atonic postpartum hemorrhage (2.98 days) and nonpostpartum hemorrhage (2.63 days); P < .001, all comparisons. Inpatient mortality rate of nonatonic postpartum hemorrhage over the entire study period was 104 per 100,000 compared to 019 per 100,000 for atonic postpartum hemorrhage and 3 per 100,000 for nonpostpartum hemorrhage deliveries (P < .001). CONCLUSION: From 2012 through 2013, women with postpartum hemorrhage experienced significantly longer length of stay and higher inpatient mortality rates than women without postpartum hemorrhage, largely attributable to nonatonic causes of postpartum hemorrhage. As hospital length of stay and inpatient mortality are important outcomes from both clinical and societal perspectives, interventions to reduce morbidity and mortality related to postpartum hemorrhage may simultaneously facilitate delivery of more cost-effective care and improve both maternal and population health.

Longitudinal association between diabetes and cognitive decline: The National Health and Aging Trends Study.

Type II diabetes mellitus (DM) is associated with increased risk of dementia; however, few studies have examined the longitudinal association between DM and cognitive outcomes in large nationally representative cohorts. We investigated these associations in 7605 participants enrolled in the National Health and Aging Trends Study, a nationally representative prospective study of Medicare beneficiaries ≥65, from 2011 to 2015. Participants or proxy respondents reported DM and dementia diagnosis, and participants completed immediate and delayed recall word list learning tests and the Clock Drawing Test. In multivariable-adjusted generalized linear mixed models, baseline DM diagnosis was associated with decline on immediate and delayed word recall and the Clock Drawing Test. In Cox proportional hazards models, DM also predicted incident dementia in older age groups at baseline. These findings further support the notion that DM is associated with cognitive outcomes, suggesting that treatment and prevention of DM may reduce the risk of these outcomes. However, more studies are needed to better understand whether DM treatments affect this relationship.

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

OBJECTIVES: To determine the cross-sectional association between cerebral amyloid-beta (Aß) deposition and gait. DESIGN: Cross-sectional. SETTING: Population-based cohort study in Olmsted County, MN. PARTICIPANTS: Cognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB-PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. MEASUREMENTS: PiB-PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor-specific regions of interest (ROIs). Gait parameters (speed, cadence, stride length, double support time, and intra-individual stance time variability) were measured using GAITRite® instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE ε4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR, and cortical thickness) in AD-associated regions. RESULTS: In fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB-PET SUVR across all ROIs was associated with slower gait speed (P < .05 except for the parietal ROI), lower cadence and longer double support time (P ≤ .05 except for the motor ROI), and greater stance time variability (P < .05). In sex-stratified analyses, the association between higher PiB-PET SUVR across all ROIs and measures of gait was only present among women. CONCLUSION: PiB-PET SUVR across ROIs, independent of general measures of AD-associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether Aß predicts gait decline in both women and men.

Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort.

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 magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented 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, fluorodeoxyglucose PET, and MRI. Baseline plasma tau levels were measured using the Quanterix Simoa-HD1 tau assay. RESULTS: Plasma tau levels were higher in MCI compared with CN (4.34 vs. 4.14 pg/mL, P = .078). In regression models adjusted for age, gender, education, and APOE, higher plasma tau was associated with worse memory performance (b = -0.30, P = .02) and abnormal cortical thickness in an AD signature region (odds ratio = 1.80, P = .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.

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 Alzheimer's 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.

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

INTRODUCTION: Few studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle-aged individuals. METHODS: We included 464 cognitively normal, test-naïve, participants with Pittsburgh compound B positron emission tomography amyloid imaging, mean age of 62.7 (range, 51-71 years), enrolled in the Mayo Clinic Study of Aging. Participants completed multiple cognitive assessments, including a standard neuropsychological battery and the CogState computerized battery, over 30 months of follow-up. Linear mixed models were used to examine the effects of amyloid and APOE genotype on baseline cognition and cognitive decline. RESULTS: Elevated amyloid was not associated with tests of episodic memory but did predict declines on tests of executive function. APOE genotype was not associated with cognition. Among APOE ɛ4 noncarriers, higher amyloid was predictive of decline on tests of executive function and on one episodic memory test. DISCUSSION: Elevated amyloidosis and APOE genotype do not appear to exert a dramatic influence on cognition in middle age.

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.