Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP)

Real-time model-based plasma state estimation, monitoring and integrated control in TCV, ASDEX-Upgrade and ITER

To maintain a high-performance, long-duration tokamak plasma scenario, it is necessary to maintain desired profiles while respecting operational limits. This requires real-time estimation of the profiles, monitoring of their evolution with respect to predictions and known limits, and their active control to remain within the desired envelope. Model-based techniques are particularly suitable to tackle such problems due to the nonlinear nature of the processes and the tight coupling among the various physical variables. A suite of physics-based, control-oriented models for the core plasma proles in a tokamak is presented, with models formulated in such a way that powerful methods from the systems and control engineering community can be leveraged to design ancient algorithms. We report on new development and applications of these models for real-time reconstruction, monitoring and integrated control of plasma proles on TCV, ASDEX-Upgrade and simulations for ITER

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

Background: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy. The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). Methods/Design: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and powe

Does Gender Influence the Relationship Between High Blood Pressure and Dementia? Highlighting Areas for Further Investigation.

BackgroundGender differences have been noted in studies linking blood pressure to all-cause dementia, and the two most common forms of dementia: Alzheimer's disease (AD) and vascular dementia (VaD). However, how gender modifies the relationship between blood pressure and dementia remains unclear.ObjectiveTo review evidence for a gender modifying effect on the link between blood pressure and all-cause dementia.MethodsA systematic review was conducted according to PRISMA guidelines. Sixteen out of 256 reviewed articles met inclusion criteria.ResultsFor women, higher midlife systolic blood pressure (SBP) and hypertension were both associated with greater risk of all-cause dementia, AD, and VaD, in six out of seven studies. Two of these studies reported higher midlife SBP/hypertension were associated with greater risk for all-cause dementia in women, but not men. One study reported higher midlife SBP associated with greater AD risk in women, but not men. However, another study reported that midlife hypertension associated with AD risk in men, but not women. No clear gender differences were reported in the relationship between late-life high blood pressure/hypertension with all-cause dementia or AD.ConclusionStudies rarely, and inconsistently, analyzed or reported gender effects. Therefore, interpretation of available evidence regarding the role of gender in blood pressure associated dementia was difficult. Several studies indicated higher midlife SBP was associated with greater risk of all-cause dementia for women, compared to men. Future studies should evaluate women-specific aging processes that occur in midlife when considering the association between blood pressure and dementia risk

Disentangling Heterogeneity in Alzheimer's Disease: Two Empirically-Derived Subtypes.

BackgroundClinical-pathological Alzheimer's disease (AD) subtypes may help distill heterogeneity in patient presentation. To date, no studies have utilized neuropsychological and biological markers to identify preclinical subtypes with longitudinal stability.ObjectiveThe objective of this study was to empirically derive AD endophenotypes using a combination of cognitive and biological markers.MethodsHierarchical cluster analysis grouped dementia-free older adults using memory, executive and language abilities, and cerebrospinal fluid amyloid-β and phosphorylated tau. Brain volume differences, neuropsychological trajectory, and progression to dementia were compared, controlling for age, gender, education, and apolipoprotein E4 (ApoE4).ResultsSubgroups included asymptomatic-normal (n = 653) with unimpaired cognition and subthreshold biomarkers, typical AD (TAD; n = 191) showing marked memory decline, high ApoE4 rates and abnormal biomarkers, and atypical AD (AAD; n = 132) with widespread cognitive decline, intermediate biomarker levels, older age, less education and more white matter lesions. Cognitive profiles showed longitudinal stability with corresponding patterns of cortical atrophy, despite nearly identical rates of progression to AD dementia.ConclusionTwo clinical-pathological AD subtypes are identified with potential implications for preventative efforts

Impulsivity and attentional bias as predictors of modafinil treatment outcome for retention and drug use in crack-cocaine dependent patients: Results of a randomised controlled trial

High impulsivity and attentional bias are common in cocaine-dependent patients and predict poor treatment outcomes. The pharmacological agent modafinil is studied for its cognitive-enhancing capacities and may therefore improve clinical outcomes in crack-cocaine dependent patients. In this study, we investigated first whether pre-treatment impulsivity and attentional bias predict treatment outcome; next whether the drug modafinil given as an add-on treatment to cognitive behavioural therapy (CBT) improves impulsivity and attentional bias; and last, whether changes in impulsivity and attentional bias are related to improvements in treatment outcome. Crack-cocaine dependent outpatients (n = 65) were randomised to 12 weeks CBT plus modafinil (400 mg/day) or only CBT. Self-reported impulsivity was assessed at baseline using the Barratt Impulsiveness Scale. At baseline and Week 12, we assessed inhibitory control as a behavioural measure of impulsivity, in terms of cognitive interference (Stroop task) and response inhibition ('stop-signal task'), and attentional bias with the addiction Stroop task. Clinical outcomes were CBT-retention and crack-cocaine use. At baseline, self-reported impulsivity predicted better CBT-retention; low self-reported and behavioural impulsivity and attentional bias predicted less crack-cocaine use. Changes in cognitive performance were not modafinil-related, but most likely due to low adherence. Improvements in impulsivity or attentional bias were not associated with CBT-retention nor changes in crack-cocaine use. Baseline impulsivity and attentional bias predicted clinical outcomes in crack-cocaine dependent patients. There were no firm indications that modafinil reduced impulsivity nor attentional bias in this population. Future studies involving cognitive-enhancing medications should include strategies to optimise adherence, to be better able to evaluate their potentia

Affective Neuropsychiatric Symptoms as Early Signs of Dementia Risk in Older Adults.

BackgroundAffective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer's disease (AD) pathophysiology.ObjectiveTo investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality.MethodsParticipants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months.ResultsLatent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles.ConclusionFindings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles