Multicenter Tract-Based Analysis of Microstructural Lesions within the Alzheimer's Disease Spectrum: Association with Amyloid Pathology and Diagnostic Usefulness.

Diffusion changes as determined by diffusion tensor imaging are potential indicators of microstructural lesions in people with mild cognitive impairment (MCI), prodromal Alzheimer's disease (AD), and AD dementia. Here we extended the scope of analysis toward subjective cognitive complaints as a pre-MCI at risk stage of AD. In a cohort of 271 participants of the prospective DELCODE study, including 93 healthy controls and 98 subjective cognitive decline (SCD), 45 MCI, and 35 AD dementia cases, we found reductions of fiber tract integrity in limbic and association fiber tracts in MCI and AD dementia compared with controls in a tract-based analysis (p < 0.05, family wise error corrected). In contrast, people with SCD showed spatially restricted white matter alterations only for the mode of anisotropy and only at an uncorrected level of significance. DTI parameters yielded a high cross-validated diagnostic accuracy of almost 80% for the clinical diagnosis of MCI and the discrimination of Aß positive MCI cases from Aß negative controls. In contrast, DTI parameters reached only random level accuracy for the discrimination between Aß positive SCD and control cases from Aß negative controls. These findings suggest that in prodromal stages of AD, such as in Aß positive MCI, multicenter DTI with prospectively harmonized acquisition parameters yields diagnostic accuracy meeting the criteria for a useful biomarker. In contrast, automated tract-based analysis of DTI parameters is not useful for the identification of preclinical AD, including Aß positive SCD and control cases.

Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer's disease (DELCODE).

BACKGROUND: Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer's disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention. METHODS: The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics. In addition, individuals with amnestic MCI, mild Alzheimer's dementia patients, first-degree relatives of patients with Alzheimer's dementia, and cognitively unimpaired control subjects are studied. The total number of subjects to be enrolled is 1000. Participants receive extensive clinical and neuropsychological assessments, magnetic resonance imaging, positron emission tomography, and biomaterial collection is perfomed. In this publication, we report cognitive and clinical data as well as apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) biomarker results of the first 394 baseline data sets. RESULTS: In comparison with the control group, patients with SCD showed slightly poorer performance on cognitive and functional measures (Alzheimer's Disease Assessment Scale-cognitive part, Clinical Dementia Rating, Functional Activities Questionnaire), with all mean scores in a range which would be considered unimpaired. APOE4 genotype was enriched in the SCD group in comparison to what would be expected in the population and the frequency was significantly higher in comparison to the control group. CSF Aß42 was lower in the SCD group in comparison to the control group at a statistical trend with age as a covariate. There were no group differences in Tau or pTau concentrations between the SCD and the control groups. The differences in all measures between the MCI group and the AD group were as expected. CONCLUSIONS: The initial baseline data for DELCODE support the approach of using SCD in patients recruited through memory clinics as an enrichment strategy for late-stage preclinical AD. This is indicated by slightly lower performance in a range of measures in SCD in comparison to the control subjects as well as by enriched APOE4 frequency and lower CSF Aß42 concentration. TRIAL REGISTRATION: German Clinical Trials Register DRKS00007966 . Registered 4 May 2015.

Paclitaxel-eluting balloon versus everolimus-eluting stent for treatment of drug-eluting stent restenosis.

OBJECTIVE: Drug-eluting stent (DES) implantation is a very effective treatment of bare-metal stent-in-stent restenosis (BMS-ISR). Therapeutic options for drug-eluting stent-in-stent restenosis (DES-ISR) are less well defined, as there are only few data on safety and effectiveness of interventional modalities. This study compared the 1-year clinical outcome after the use of drug-eluting balloon (DEB) to second-generation everolimus-eluting stent (EES) for treatment of DES-ISR. METHODS: This observational study included 86 patients with 86 DES-ISR. Forty patients were treated by repeat percutaneous coronary intervention (PCI) using an EES. Forty-six patients were treated by repeat PCI using a DEB. Follow-up periods were 22 ± 11 and 25 ± 19 months, respectively. The primary endpoint of the study was survival free of major adverse cardiac events (MACEs) at 1 year. Secondary endpoints were needed for target lesion revascularization (TLR), definite stent thrombosis (ST) at 1 year, and MACE rate during total follow-up period. RESULTS: Baseline clinical and angiographic parameters were comparable between the two groups. EES were associated with a higher MACE rate at 1 year compared to DEB (27.5 vs. 8.6%, respectively; P = 0.046). TLR rates for EES and DEB were 22.5% versus 4.3%, respectively, P = 0.029, while rates of definite ST at 1 year follow-up were comparable (2.5% vs. 0%, respectively; P = 0.945). There were no differences in myocardial infarction rates between the two groups (5% vs. 2%, respectively; P = 0.595) and in mortality. Considering the complete follow-up periods, DEB were associated with significantly less MACE compared to EES (log-rank test, P = 0.045). Furthermore, comparison of TLR rates showed a strong trend in favor of DEB compared to EES (P = 0.074). CONCLUSIONS: Treatment of DES-ISR using a DEB is associated with favorable rates of MACE and TLR at 1-year follow-up compared to the implantation of an EES.

Three-year follow-up after treatment of bare-metal stent restenosis with first-generation or second-generation drug-eluting stents.

AIMS: First-generation drug-eluting stents have been proven to be very effective for the treatment of bare-metal stent in-stent restenosis (BMS ISR). Efficacy of second-generation drug-eluting stents in this setting remains less well defined. This study compared 3-year clinical outcomes after treatment of BMS ISR using second-generation everolimus-eluting stents (EES) to first-generation paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES). METHODS: This was a retrospective observational study. A total of 264 consecutive patients with BMS ISR underwent percutaneous coronary intervention using EES (75 patients), PES (95 patients), or SES (94 patients) from 2003 to 2009. The primary endpoint of the study was survival free of major adverse cardiac events (MACE) at 3 years. Secondary endpoints were survival free of need for revascularization of the target lesion and definite stent thrombosis. Clinical follow-up could be obtained in 99% of patients. RESULTS: Baseline clinical and angiographic parameters were comparable between the three groups. MACE at the 3-year follow-up were 27, 30, and 27%, for the EES, PES, and SES groups, respectively (P=0.874). The target lesion revascularization rates for EES, PES, and SES groups were 15, 20, and 23%, respectively (P=0.429). Rates of definite stent thrombosis at the 3-year follow-up were comparable between the three groups at 0, 2.1, and 1.0%, respectively (P=0.437). Rates of myocardial infarction and death were also similar between the three groups. Diabetes mellitus was the only independent predictor of MACE at the 3-year follow-up (odds ratio=1.14, 95% confidence interval 1.00-1.30; P=0.038), whereas renal insufficiency was the only independent predictor for death (odds ratio=1.10, 95% confidence interval 0.850-1.274; P=0.011). CONCLUSION: Second-generation EES is as effective and safe as the first-generation PES or SES in the treatment of BMS ISR. Diabetes mellitus is the only independent predictor for MACE at the long-term follow-up.

Effectiveness of everolimus-eluting stents in the treatment of drug-eluting stent versus bare-metal stent restenosis.

BACKGROUND: The efficacy of drug-eluting stents (DES) for the treatment of in-stent restenosis (ISR) after DES implantation is not well defined. This study compared the clinical outcome after the use of everolimus-eluting stents (EES) for the treatment of bare-metal stent (BMS) versus DES restenosis. METHOD: Ninety-four patients with 94 ISR were included in this study. Sixty-four patients had BMS-ISR and 30 patients had DES-ISR. Patients were treated by repeat PCI using an EES. The primary endpoint of the study was survival free of target lesion revascularization (TLR) at 12 months or DES-ISR versus BMS-ISR patients. The secondary endpoints were survival free of major adverse cardiac events (MACE) and definite stent thrombosis. RESULTS: The baseline clinical and angiographic parameters were comparable between the two groups. Treatment of DES-ISR was associated with higher rates of recurrent TLR, myocardial infarction (MI), and MACE at the 12-month follow-up compared with the treatment of BMS-ISR (23.3 versus 1.6%, P=0.002 for TLR; 13.3 versus 0%, P=0.017 for MI; and 30 versus 4.6%, P=0.003 for MACE). There were no differences in mortality and definite stent thrombosis between both groups (P=0.5686 and 0.6927, respectively). Initial stent number (odds ratio=1.13, 95% confidence interval 1.02-1.25; P=0.024) and initial stent type being a DES (odds ratio=8.11, 95% confidence interval 5.99-10.45; P<0.001) were independent predictors of recurrent TLR after the treatment of ISR using an EES. CONCLUSION: EES used for the treatment of DES-ISR is associated with higher rates of recurrent revascularization, MI, and MACE compared with EES for the treatment of BMS-ISR.

Everolimus-eluting versus paclitaxel-eluting stents for treatment of bare metal stent restenosis.

First-generation drug-eluting stents have been proved to be very effective for the treatment of bare metal stent in-stent restenosis (BMS ISR). The efficacy of second-generation drug-eluting stents in this setting remains less well defined. The present study compared the long-term clinical outcome after treatment of BMS ISR using the second-generation everolimus-eluting stent (EES) to that after treatment using the paclitaxel-eluting stent (PES). A total of 174 patients with BMS ISR underwent percutaneous coronary intervention using a PES (95 patients) or an EES (79 patients) from 2003 to 2010. The patients in the PES and EES groups were followed up for 42.2 ± 22.2 and 18.3 ± 8.2 months, respectively. The primary end point of the study was survival free of major adverse cardiac events at 1 year. The secondary end points were survival free of the need for revascularization of the target lesion and definite stent thrombosis. The baseline clinical and angiographic parameters were comparable between the 2 groups. The freedom from major adverse cardiac event rate at 1 year of follow-up was 4.5% and 13.6% (p = 0.0663) for the EES and PES groups, respectively. The target lesion revascularization (TLR) rates were greater in the PES group at 1 year of follow-up compared to the EES group (1% vs 11.5%, p = 0.0193). The rate of myocardial infarction, death, and definite stent thrombosis for the EES and PES groups at 1 year of follow-up was 0% versus 4.2% (p = 0.0984), 3% versus 2.1% (p = 0.6855), and 0% versus 2.1% (p = 0.2382), respectively. The use of a PES for treatment of ISR was the only independent predictor of recurrent TLR at 1 year of follow-up (odds ratios 1.11, 95% confidence interval 1.05 to 1.18; p = 0.0193). During the complete follow-up period, the rates of TLR, myocardial infarction, death, major adverse cardiac events, and definite stent thrombosis were not different between the 2 treatment groups. In conclusion, EES resulted in reduced rates of TLR at 1 year of follow-up compared to PES when used for treatment of BMS ISR. However, at long-term follow-up, the event rates between EES and PES were comparable after treatment of BMS ISR.