Vascular risk factors affect cerebral blood flow (CBF) and cerebral vascular reactivity, contributing to cognitive decline. Hippocampus is vulnerable to both Alzheimer's disease (AD) pathology and ischemia; nonetheless, the information about the impact of vascular risk on hippocampal perfusion is minimal. Cognitively, healthy elderly (NL = 18, 69.9 ± 6.7 years) and subjects with mild cognitive impairment (MCI = 15, 74.9 ± 8.1 years) were evaluated for the Framingham cardiovascular risk profile (FCRP). All underwent structural imaging and resting CBF assessment with arterial spin labeling (ASL) at 3T magnetic resonance imaging (MRI). In 24 subjects (NL = 17, MCI = 7), CBF was measured after a carbon dioxide rebreathing challenge. Across all subjects, FCRP negatively correlated with hippocampal (q = À0.41, P = 0.049) and global cortical (q = À0.46, P = 0.02) vasoreactivity to hypercapnia (VR h ). The FCRP-VR h relationships were most pronounced in the MCI group: hippocampus (q = À0.77, P = 0.04); global cortex (q = À0.83, P = 0.02). The FCRP did not correlate with either volume or resting CBF. The hippocampal VR h was lower in MCI than in NL subjects (Z = À2.0, P = 0.047). This difference persisted after age and FCRP correction (F [3,20] = 4.6, P = 0.05). An elevated risk for vascular pathology is associated with a reduced response to hypercapnia in both hippocampal and cortical tissue. The VR h is more sensitive to vascular burden than either resting CBF or brain volume.

Objectives: This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD.Methods: Fifty-two NL individuals received MRI, 11 C-Pittsburgh compound B (PiB)-PET, and 18 F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n 5 13/group, aged 32-72 years, 60% female, 30% APOE e4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH2). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volumecorrected PiB retention, and FDG metabolism across FH groups and vs FH2. Alzheimer disease (AD) is an age-related neurodegenerative disease and the most common form of dementia. Clinical studies indicate that by the time patients seek diagnosis, the amount of irreversible brain damage that may have already occurred hinders treatment potential. Effective interventions, as they become available, ideally would be implemented in at-risk individuals before symptoms occur.Having a family history (FH) of AD is a major risk factor for developing the disease. 1,2 While the rare early-onset forms of AD (EOAD) have autosomal dominant genetic inheritance, the risk of developing late-onset AD (LOAD) (i.e., .99% of the AD population older than 60 years) is influenced by genetic and nongenetic factors.1 Although LOAD does not show recognizable mendelian inheritance, risk is to some extent genetically determined, as shown by the familial aggregation of many cases.2 Among probands, those with a parent affected by LOAD are at particularly high risk, 3,4 and the risk is higher still when both parents are affected. [5][6][7] However, because only ,5% of individuals have both parents affected by LOAD, 2,5-7 the clinical profile associated with this rare circumstance has been poorly studied and epidemiologic findings have not been characterized by the use of biomarkers.

Introduction Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions. Methods We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts’ definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology. Results We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs No TDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88–1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the no TDM group [RR: 0.60; 95% CI 0.35–1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15–0.32]. PICO 4 TDM [proactive/reactive] vs No TDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77–1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE. Conclusions This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.

Background and Aims Quality metrics were established to develop standards to help assess quality of care, yet variation in inflammatory bowel disease [IBD] clinical practice exists. We performed a systematic review to assess the overall quality of evidence cited in formulating IBD quality metrics. Methods A systematic search was performed on PubMed, MEDLINE, and EMBASE. All major national and international IBD societies were included. Quality metrics were assessed for evidence quality and categorised as category A [guideline based], category B [primarily retrospective and observational studies], or category C [expert opinion]. Quality metrics were examined for the type of metric, and the quality, measurability, review, existing conflicts of interest [COI], and patient participation of the metric. Statistical analysis was conducted in R. Results A total of 143 distinct, and an aggregate total of 217 quality metrics were included and analysed; 68%, 3.2%, and 28.6% of IBD quality metrics were based on low, moderate, and high quality of evidence, respectively. The proportion of high-quality evidence across societies was significantly different [p <0.01]. Five organisations included patients in quality metric development, three reported external review, not all reported measurable outcomes or stated the presence of a COI. Finally, 43% of quality metrics were published more than 5 years ago. Conclusions Quality metrics are important to standardise practice. As more than two-thirds of the quality metrics in IBD are based on low-quality evidence, further studies are needed to improve the overall quality of evidence supporting the development of quality measures.

Background Guidelines are published by international gastroenterology societies regarding the management of ulcerative colitis (UC) and Crohn’s disease (CD) to help clinicians to provide high-quality patient care. We examined the guidelines for the quality and strength of evidence used to develop the recommendations, methods for grading evidence, differences in disease-specific recommendations, conflicts of interest, and plans for guideline updates. Methods A systematic search was performed on PubMed using “ulcerative colitis,” “Crohn’s disease,” and “guidelines” in April 2019. International gastroenterology society websites were searched for UC- and CD-specific guidelines. Guidelines from 12 societies were examined by two authors. Chi-squared tests were used for comparing evidence-level grades, strength of recommendations, and reported conflicts of interest. Linear-regression modeling was used to evaluate the relationship between the number of authors and the number of recommendations in a given guideline. Results Of 28 guidelines reviewed, 25 (89%) used a total of three different systems to grade the level of evidence and 2 (7%) used an unknown system. Three (11%) reviewed guidelines did not provide a conflict-of-interest statement, while three (11%) provided a timeline for guideline updates. Of 1,265 total statements examined, 246 (19%) reported no grade of evidence quality or explicitly stated that the recommendation was based on “expert opinion.” One hundred and thirty-five (22%) UC recommendations were noted to be “weak/conditional” and 95 (16%) did not have a recommendation strength. Two hundred and forty-two (37%) CD recommendations were noted to be “weak/conditional” and 151 (23%) did not have a recommendation strength. Conclusion The majority of UC and CD guidelines are based on a low/very low quality of evidence and are further weakened due to the lack of homogeneity in specific aspects of management recommendations as well as conflicts of interest.

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