Estimation of Survival Rates from a Jolly-Seber Model with Tag Loss

22 pages, 1 article*Estimation of Survival Rates from a Jolly-Seber Model with Tag Loss* (Kremers, Walter K.) 22 page

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging

Objective Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain‐specific cognitive trajectories. Methods In this longitudinal study conducted in the setting of the population‐based Mayo Clinic Study of Aging, 5081 community‐dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI‐Q), and Beck Depression and Anxiety Inventories (BDI‐II, BAI). Global and domain‐specific (memory, language, attention, and visuospatial skills) cognitive performance was assessed through neuropsychological testing every 15 months. Associations between baseline NPS and trajectories for individual yearly change in cognitive z‐scores were calculated using linear mixed‐effect models. Results Cognition declined regardless of NPS status over the median follow‐up of 4.5 years. Presence of NPS was associated with increased cognitive decline. Differences in annualized change in global cognition z‐scores for participants with NPS compared to without NPS ranged from −0.018 (95% CI −0.032, −0.004; p = 0.011) for irritability to −0.159 (−0.254, −0.065; p = 0.001) for hallucinations. Associations between NPS and annual decline in global cognition were significant for most NPI‐Q‐assessed NPS and clinical depression (BDI‐II≥13). Participants with NPI‐Q‐assessed depression, apathy, nighttime behavior, and clinical depression had greater decline in all domain‐specific z‐scores; presence of delusions and anxiety was associated with more pronounced decline in language, attention and visuospatial skills. Conclusion NPS were associated with a more accelerated cognitive decline. Clinical assessment and potential treatment of NPS is warranted even in a community setting as NPS may impact cognitive decline in nondemented individuals

Clinical and kidney structural characteristics of living kidney donors with nephrolithiasis and their long-term outcomes

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function. Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (\u3e5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including review of metabolic evaluations in stone formers. Long-term risks of renal complications (low eGFR and hypertension) by stone former status were evaluated. Results: There were 12 symptomatic and 76 asymptomatic stone formers among 866 donors. Overall, baseline clinical characteristics and implantation biopsy findings were similar between stone formers and non-stone formers. After a median follow-up of 10 y, stone former status was not associated with eGFR \u3c60 mL/min/1.73 m2, eGFR \u3c45 mL/min/1.73 m Conclusions: Both asymptomatic and symptomatic SF have favorable histology findings at baseline. Long-term kidney outcomes were favorable in select stone formers with no evident increased long-term risk for decreased kidney function or hypertension after donation

Association between CSF biomarkers of Alzheimer\u27s disease and neuropsychiatric symptoms: Mayo Clinic Study of Aging

INTRODUCTION: We examined the association between cerebrospinal fluid (CSF)-derived biomarkers of Alzheimer\u27s disease and neuropsychiatric symptoms (NPS) in older non-demented adults. METHODS: We included 784 persons (699 cognitively unimpaired, 85 with mild cognitive impairment) aged ≥ 50 years who underwent CSF amyloid beta (Aβ42), hyperphosphorylated tau 181 (p-tau), and total tau (t-tau) as well as NPS assessment using Beck Depression and Anxiety Inventories (BDI-II, BAI), and Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: Lower CSF Aβ42, and higher t-tau/Aβ42 and p-tau/Aβ42 ratios were associated with BDI-II and BAI total scores, clinical depression (BDI-II ≥ 13), and clinical anxiety (BAI ≥ 10), as well as NPI-Q-assessed anxiety, apathy, and nighttime behavior. DISCUSSION: CSF Aβ42, t-tau/Aβ42, and p-tau/Aβ42 ratios were associated with NPS in community-dwelling individuals free of dementia. If confirmed by a longitudinal cohort study, the findings have clinical relevance of taking into account the NPS status of individuals with abnormal CSF biomarkers

Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival

ObjectivesTransplantation is limited by a lack of human organ donors. Organs derived from animals, most likely the pig, represent a potential solution to this problem. For the heart, 90-day median graft survival of life-supporting pig hearts transplanted to nonhuman primates has been considered a reasonable standard for entry into the clinical arena. Overcoming the immune barrier to successful cardiac xenotransplantation is most appropriately first explored with the non–life-supporting heterotopic model.MethodsWe performed a series of 7 heterotopic heart transplantations from CD46 transgenic pigs to baboons using a combination of therapeutic agents largely targeted at controlling the synthesis of anti-pig antibodies. Rituximab (anti-CD20) and Thymoglobulin (rabbit antithymocyte globulin [ATG]; SangStat Medical Corp, Fremont, Calif) were used as induction therapy. Baseline immunosuppression consisted of splenectomy, tacrolimus, sirolimus, steroids, and TPC (an anti-Gal antibody therapeutic). Rejection events were not treated.ResultsBy using Kaplan-Meier analysis, median graft survival was 96 days (range, 15–137 days; 95% confidence interval, 38–99 days). Only 2 grafts were lost as a result of rejection, as defined by cessation of graft palpation. There was no evidence of a consumptive coagulopathy, infectious complications were treatable, and no posttransplantation lymphoproliferative disorders occurred. No cellular infiltration was observed.ConclusionsThis study reports the longest median survival to date (96 days) of pig hearts transplanted heterotopically into baboons. Duplication of these results in the orthotopic life-supporting position could bring cardiac xenotransplantation to the threshold of clinical application

Physical Activity and Trajectory of Cognitive Change in Older Persons: Mayo Clinic Study of Aging

Background: Little is known about the association between physical activity (PA) and cognitive trajectories in older adults. Objective: To examine the association between PA and change in memory, language, attention, visuospatial skills, and global cognition, and a potential impact of sex or Apolipoprotein E (APOE) epsilon 4 status. Methods: Longitudinal study derived from the population-based Mayo Clinic Study of Aging, including 2,060 cognitively unimpaired males and females aged >= 70 years. Engagement in midlife (ages 50-65) and late-life (last year) PA was assessed using a questionnaire. Neuropsychological testing was done every 15 months (mean follow-up 5.8 years). We ran linear mixed-effect models to examine whether mid- or late-life PA at three intensities (mild, moderate, vigorous) was associated with cognitive z-scores. Results: Light intensity midlife PA was associated with less decline in memory function compared to the no-PA reference group (time x light PA; estimate [standard error] 0.047 [0.016], p = 0.004). Vigorous late-life PA was associated with less decline in language (0.033 [0.015], p = 0.030), attention (0.032 [0.017], p = 0.050), and global cognition (0.039 [0.016], p = 0.012). Females who were physically inactive in midlife experienced more pronounced cognitive decline than females physically active in midlife and males regardless of PA (p-values for time interaction terms with midlife PA levels and sex were all p < 0.05 for global cognition). APOE epsilon 4 carriership did not moderate the association between PA and cognition. Conclusion: Engaging in PA, particularly of vigorous intensity in late-life, was associated with less pronounced decline in global and domain-specific cognition. This association may differ by sex

Plasma‐derived biomarkers of Alzheimer\u27s disease and neuropsychiatric symptoms: A community‐based study

INTRODUCTION: We examined associations between plasma-derived biomarkers of Alzheimer\u27s disease (AD) and neuropsychiatric symptoms (NPS) in community-dwelling older adults. METHODS: Cross-sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma-derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p-tau181], p-tau217, total tau [t-tau], neurofilament light [NfL]), and NPS assessment. RESULTS: P-tau181 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.41–3.00, p < 0.001), p-tau217 (OR 1.70, 95% CI 1.10–2.61, p = 0.016), and t-tau (OR 1.44, 95% CI 1.08–1.92, p = 0.012) were associated with appetite change. We also found that p-tau181 and p-tau217 were associated with increased symptoms of agitation (OR 1.93, 95% CI 1.20–3.11, p = 0.007 and OR 2.04, 95% CI 1.21–3.42, p = 0.007, respectively), and disinhibition (OR 2.39, 95% CI 1.45–3.93, p = 0.001 and OR 2.30, 95% CI 1.33–3.98, p = 0.003, respectively). Aβ42/Aβ40 and NfL were not associated with NPS. CONCLUSION: Higher plasma-derived p-tau181 and p-tau217 levels are associated with increased symptoms of appetite change, agitation, and disinhibition. These findings may support the validity of plasma tau biomarkers for predicting behavioral symptoms that often accompany cognitive impairment. HIGHLIGHTS - We studied 1005 community-dwelling persons aged ≥ 50 years - Higher plasma tau levels are associated with increased neuropsychiatric symptoms - Aβ42/Aβ40 and NfL are not associated with neuropsychiatric symptoms - Clinicians should treat neuropsychiatric symptoms in persons with high plasma-derived ta