Causes and Rates of 30-day Readmissions after Percutaneous Transhepatic Biliary Drainage Procedure.

Purpose To investigate rates and causes of 30-day readmission for patients who undergo percutaneous transhepatic biliary drainage (PTBD) procedures. Materials and Methods In this retrospective study, PTBD procedures performed at a tertiary care institution (June 2008 to May 2013) were reviewed. For each patient, the first 30-day readmission was used to determine cause of readmission. Two interventional radiologists independently categorized causes for readmission as planned or unplanned, and unplanned causes as related to or unrelated to interventional radiology. Interventional radiology-related readmissions were categorized as potentially preventable or unpreventable. Factors associated with higher odds for 30-day readmission were identified with univariable and multivariable analysis. Results There were 266 procedures in 266 patients (mean age, 67 years; interquartile range, 57-76 years; 53.4% men). The cause of obstruction was malignant in 50.0% of patients (133 of 266). There were 122 of 266 patients (45.9%) readmitted within 30 days. Of these readmissions, 44 of 122 (36.1%) were planned and 78 of 122 (63.9%) were unplanned. A majority of unplanned readmissions (57 of 78; 73%) were related to interventional radiology. Of unplanned interventional radiology-related readmissions, 16% (nine of 57) were related to periprocedural complications and 51% (29 of 57) were considered preventable. At multivariable analysis, Medicaid insurance (odds ratio, 3.68; 95% confidence interval: 1.52, 9.99; P = .009) and bilateral PTBDs (odds ratio, 5.81; 95% confidence interval: 1.79, 18.90; P = .003) were associated with 30-day readmission. Conclusion Thirty-day readmissions after primary biliary drainage are common and a majority of unplanned readmissions are drain-related. Nearly half of unplanned interventional radiology-related readmissions are potentially preventable. © RSNA, 2018 See also the editorial by Nikolic in this issue.

Brain atrophy rates in first degree relatives at risk for Alzheimer's.

A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p < 0.01), entorhinal cortex (p < 0.01), hippocampus (p < 0.053) and cortical gray matter (p < 0.009). However, when E4 genotype was added as a covariate, none of the FH effects remained significant. Analyses by ApoE genotype showed that the effect of FH on amygdala atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH- subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.

Educational attainment and hippocampal atrophy in the Alzheimer's disease neuroimaging initiative cohort.

INTRODUCTION: Subjects with higher cognitive reserve (CR) may be at a lower risk for Alzheimer's disease (AD), but the neural mechanisms underlying this are not known. Hippocampal volume loss is an early event in AD that triggers cognitive decline. MATERIALS AND METHODS: Regression analyses of the effects of education on MRI-measured baseline HV in 675 subjects (201 normal, 329 with mild cognitive impairment (MCI), and 146 subjects with mild AD), adjusting for age, gender, APOE ɛ4 status and intracranial volume (ICV). Subjects were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large US national biomarker study. RESULTS: The association between higher education and larger HV was significant in AD (P=0.014) but not in cognitively normal or MCI subjects. In AD, HV was about 8% larger in a person with 20 years of education relative to someone with 6 years of education. There was also a trend for the interaction between education and APOE ɛ4 to be significant in AD (P=0.056). CONCLUSION: A potential protective association between higher education and lower hippocampal atrophy in patients with AD appears consistent with prior epidemiologic data linking higher education levels with lower rates of incident dementia. Longitudinal studies are warranted to confirm these findings.

Mapping the effect of the apolipoprotein E genotype on 4-year atrophy rates in an Alzheimer disease-related brain network.

PURPOSE: To determine the effect of the apolipoprotein E (APOE) genotype on atrophy rates of specific brain gray matter regions hypothesized to be key components of cognitive networks disrupted in Alzheimer disease. MATERIALS AND METHODS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All subjects and their legal representatives gave written informed consent prior to data collection. The authors analyzed data from 237 subjects (mean age, 79.9 years; 40% female) with mild cognitive impairment (MCI) in the ADNI database and assessed the effect of the APOE ε4 and ε2 alleles on regional brain atrophy rates over a 12-48-month period. Brain regions were selected a priori: 15 experimental and five control regions were included. Regional atrophy rates were derived by using a fully automated algorithm applied to T1-weighted magnetic resonance (MR) imaging data. Analysis consisted of mixed-effects linear regression with repeated measures; results were adjusted for multiple testing with Bonferroni correction. RESULTS: Thirteen of 15 experimental regions showed a significant effect of ε4 for higher atrophy rates (P < .001 for all). Cohen d values ranged from 0.26 to 0.42, with the largest effects seen in the amygdalae and hippocampi. The transverse temporal cortex showed a trend (P = .02, but did not survive Bonferroni correction) for a protective effect (Cohen d value = 0.15) of ε2. No control region showed an APOE effect. CONCLUSION: The APOE ε4 allele is associated with accelerated rates of atrophy in 13 distinct brain regions in limbic and neocortical areas. This suggests the possibility of a genotype-specific network of related brain regions that undergo faster atrophy in MCI and potentially contribute to cognitive decline. Online supplemental material is available for this article.

Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.

OBJECTIVE: A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum. DESIGN: Cross-sectional analyses of data from a national biomarker study. SETTING: The Alzheimer's Disease Neuroimaging Initiative national study. PATIENTS: 257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data. OUTCOME MEASURES: Cerebrospinal fluid (CSF) Aß42, tau, and tau/Aß42 ratio, MRI-measured hippocampal volumes. STATISTICS: Univariate and multivariate analyses. RESULTS: In MCI, CSF Aß42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aß42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aß42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group. CONCLUSIONS: A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.

Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth.

BACKGROUND: Although it is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis. METHODS: We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55-94 years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD). FINDINGS: In a model incorporating multiple predictive factors, the effect of apolipoprotein E ε4 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p<0.0001). The effect of apolipoprotein E ε4 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p<0.0001). Surprisingly, ApoE ε4+ normal controls had greater mean plaque density across all cortical regions than ε4- EMCI and ε4- LMCI (p<0.0001, p=0.0009) and showed higher, though non-significant, mean value than ε4- AD patients (p<0.27). ApoE ε4+ EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than ε4- AD patients (p<0.027, p<0.0001). INTERPRETATION: Neuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data also provides additional evidence for a temporal offset between amyloid deposition and clinically relevant symptoms.

Dissecting the gene dose-effects of the APOE ε4 and ε2 alleles on hippocampal volumes in aging and Alzheimer's disease.

OBJECTIVE: To investigate whether there is a specific dose-dependent effect of the Apolipoprotein E (APOE) ε4 and ε2 alleles on hippocampal volume, across the cognitive spectrum, from normal aging to Alzheimer's Disease (AD). MATERIALS AND METHODS: We analyzed MR and genetic data on 662 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database-198 cognitively normal controls (CN), 321 mild-cognitive impairment (MCI) subjects, and 143 AD subjects-looking for dose-dependent effects of the ε4 and ε2 alleles on hippocampal volumes. Volumes were measured using a fully-automated algorithm applied to high resolution T1-weighted MR images. Statistical analysis consisted of a multivariate regression with repeated-measures model. RESULTS: There was a dose-dependent effect of the ε4 allele on hippocampal volume in AD (p = 0.04) and MCI (p = 0.02)-in both cases, each allele accounted for loss of >150 mm(3) (approximately 4%) of hippocampal volume below the mean volume for AD and MCI subjects with no such alleles (Cohen's d = -0.16 and -0.19 for AD and MCI, respectively). There was also a dose-dependent, main effect of the ε2 allele (p<0.0001), suggestive of a moderate protective effect on hippocampal volume-an approximately 20% per allele volume increase as compared to CN with no ε2 alleles (Cohen's d = 0.23). CONCLUSION: Though no effect of ε4 was seen in CN subjects, our findings confirm and extend prior data on the opposing effects of the APOE ε4 and ε2 alleles on hippocampal morphology across the spectrum of cognitive aging.