Abstract The pathway leading from beta-amyloid deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer’s disease (AD). However, what drives amyloid ...build-up in sporadic non-genetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (i) GMB taxa with pro- and anti-inflammatory activity, and (ii) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa ( Escherichia/Shigella, Pseudomonas aeruginosa , Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii and Bacteroides fragilis ) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, IL-1β, IL-6, IL-18, IL-8, NLRP3, TNF-α; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n=40, Amy+) and with no brain amyloidosis (n=33, Amy-), and also in a group of controls (n=10, no brain amyloidosis and no cognitive impairment, HC). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3 and IL-1β) compared to both controls and to Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of Eubacterium rectale and higher abundance of Escherichia/Shigella as compared to both HC (Fold Change, FC=-9.6, p<0.001 and FC=+12.8, p<0.001, respectively ) and to Amy- (FC=-7.7, p<0.001 and FC=+7.4, p=0.003 ). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3 and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho=0.60, p<0.001; rho=0.57, p<0.001; and rho=0.30, p=0.007, respectively) and a negative correlation with the anti-inflammatory Eubacterium rectale ( rho=-0.48, p<0.001; rho=-0.25, p=0.024; rho=-0.49, p<0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella , and a reduction in the abundance of an anti-inflammatory taxon, Eubacterium rectale , are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.
Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a ...coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.
Abstract Background Infective endocarditis (IE) can be complicated by intracranial bleeding (ICB) caused by different pathologic mechanisms. The occurrence of ICB in patients with IE significantly ...influences therapeutic decisions and has a negative impact on outcome. Case Report We describe the clinical courses of 3 patients with aortic prosthetic valve IE presenting with ICB. Patients 1 and 2 experienced subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), respectively, caused by rupture of an intracranial infectious aneurysm (IIA). Both underwent endovascular treatment of IIA with good outcome. In patient 3, ICB was the hemorrhagic conversion of an acute ischemic lesion from septic brain embolization. In the subacute phase of the disease, aortic valve replacement was performed, with excellent outcome. Why Should an Emergency Physician be Aware of This? ICB is a relevant complication and sometimes the first clinical feature of IE. Imaging of brain vessels should be performed to investigate the pathologic mechanism underlying ICB. The prevalence of IIA is probably underestimated and may influence the therapeutic strategy. Cerebrovascular imaging may therefore also be considered in asymptomatic subjects with left-sided IE. Withdrawal of anticoagulant treatment and delay of cardiac surgery are recommended in all cases of IE complicated by ICB. Because of the impact of ICB on IE management and outcome, a high level of clinical suspicion and prompt recognition and treatment of this complication are necessary.
Abstract Bellelli G, Buccino G, Bernardini B, Padovani A, Trabucchi M. Action observation treatment improves recovery of postsurgical orthopedic patients: evidence for a top-down effect? Objective To ...assess whether action observation treatment (AOT) may also improve motor recovery in postsurgical orthopedic patients, in addition to conventional physiotherapy. Design Randomized controlled trial. Setting Department of rehabilitation. Participants Patients (N=60) admitted to our department postorthopedic surgery were randomly assigned to either a case (n=30) or control (n=30) group. Exclusion criteria were age 18 years or younger and 90 years or older, Mini-Mental State Examination score of 21 of 30 or lower, no ambulating order, advanced vision impairment, malignancy, pneumonia, or heart failure. Interventions All participants underwent conventional physiotherapy. In addition, patients in the case group were asked to observe video clips showing daily actions and to imitate them afterward. Patients in the control group were asked to observe video clips with no motor content and to execute the same actions as patients in the case group afterward. Participants were scored on functional scales at baseline and after treatment by a physician blinded to group assignment. Main Outcomes Measures Changes in FIM and Tinetti scale scores, and dependence on walking aids. Results At baseline, groups did not differ in clinical and functional scale scores. After treatment, patients in the case group scored better than patients in the control group (FIM total score, P =.02; FIM motor subscore, P =.001; Tinetti scale score, P =.04); patients in the case group were assigned more frequently to 1 crutch ( P =.01). Conclusions In addition to conventional physiotherapy, AOT is effective in the rehabilitation of postsurgical orthopedic patients. The present results strongly support top-down effects of this treatment in motor recovery, even in nonneurologic patients.
To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to ...report the prevalence and clinical profile of subtypes of delirium in a multicenter study.
This is a point prevalence study nested in the "Delirium Day 2015", which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes.
Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9).
The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium.
Objective Stroke is an important risk factor for dementia, but the exact mechanism involved in cognitive decline remains unclear. Methods Patients were divided into 2 groups: poststroke dementia ...group (PSD) and poststroke nondementia group (PSND). Variables and neuroradiological hallmarks were compared between 2 groups at 3 months (114 subjects) and 1 year (105 subjects) after stroke. Results Older age (OR 1.11, 95% CI 1.0-1.2; P < .05), education (OR .6, 95% CI .4-.8; P < .05), prestroke IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly; OR .78, 95% CI .1-5.9; P < .05), premorbid apathy (OR 2.03, 95% CI 1.1-3.7; P < .05), and medial temporal lobe atrophy (MTLA) (OR 6.14, 95% CI 1.4-26.2; P < .05) were independently associated with PSD at 3 months after a cerebrovascular event, whereas at 1-year follow-up older age (OR 1.1, 95% CI 1.0-1.2; P < .05), prestroke IQCODE (OR .05, 95% CI .0-.9; P < .05), MTLA (OR 1.3, 95% CI 1.0-1.6; P < .05), and APACHE II (Acute Physiology and Chronic Health Evaluation; OR .6, 95% CI .4-.9; P < .05) were independently associated with PSD. Conclusions Acute cerebrovascular disease could not be the only one mechanism explaining PSD. Neurodegenerative pathology must be taken into account.
We have described a case of a suspected transient ischemic attack with a double lumen potentially resembling a dissection of the internal carotid artery on Doppler ultrasound. The identification of ...an arterial branch from the internal carotid artery and flowing near it using magnetic resonance imaging suggested an aberrant origin of an ascending pharyngeal artery or occipital artery. Performance of the occipital tap maneuver in the occipital artery perfusion territory demonstrated a reflected flow in the double lumen, supporting the aberrant origin of the occipital artery from the internal carotid artery. The occipital tap maneuver can represent an easy-to-do procedure to distinguish anatomic variants and study double-lumen findings.
Objectives: To investigate the effect of cardiovascular changes (i.e., QT interval, QT dispersion (QTD), heart rate variability (HRV), and other cardiovascular measures) in subjects with Alzheimer's ...disease (AD) and mild cognitive impairment (MCI).
Design: Each subject underwent clinical and cognitive examination, a structural brain imaging study, echocardioDoppler, electrocardiogram (ECG), HRV analysis using 24‐hour ECG monitoring, and 24‐hour blood pressure monitoring.
Setting: Community population‐based sample of patients admitted to an AD center for investigation of cognitive disturbances.
Participants: Thirty‐three subjects with AD, 39 subjects with MCI, and 29 cognitive healthy subjects (controls) matched for demographic characteristics, hypertensive condition, smoking habits, and laboratory parameters were enrolled consecutively.
Measurements: Clinical and cognitive examination, structural brain imaging study, echocardioDoppler, ECG, HRV analysis using 24‐hour ECG monitoring, and 24‐hour blood pressure monitoring.
Results: QTD and QT corrected dispersion mean values were significantly higher in patients with AD than in patients with MCI and controls and higher in patients with MCI than in controls. HRV time and domain parameters were lower in patients with AD than in patients with MCI and controls. No difference in other cardiovascular measures was found. QTD and HRV were found to be significantly correlated with the degree of cognitive impairment.
Conclusion: These findings support the presence of a peculiar neuroanatomic dysfunction in patients with AD and MCI that parallels the disease progression. These noninvasive parameters might prove to be powerful predictive tools in the worsening of cognitive function and mortality risk.
Background and Purpose The aim of this study was to investigate for a possible association between both prestroke CHA2 DS2 -VASc score and the severity of stroke at presentation, as well as ...disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2 DS2 -VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS ≥10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS <3 or ≥3). Multiple logistic regression was used to correlate prestroke CHA2 DS2 -VASc and severity of stroke, as well as disability and mortality at 90 days. Results Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS ≥3. A linear correlation was found between the prestroke CHA2 DS2 -VASc score and severity of stroke ( P = .001). On multivariate analysis, CHA2 DS2 -VASc score correlated with severity of stroke ( P = .041) and adverse functional outcome (mRS ≥3) ( P = .001). A logistic regression with the receiver operating characteristic graph procedure ( C -statistics) evidenced an area under the curve of .60 ( P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA2 DS2 -VASc score and lesion size. Conclusions In patients with AF, in addition to the risk of stroke, a high CHA2 DS2 -VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.
Summary Background Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based ...diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand123 I-2β-carbometoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123 I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. Methods We did a phase III study in which we used a123 I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0·80) and specificity (0·85) targets and prespecified lower thresholds (sensitivity 0·65, specificity 0·73) using one-sided binomial tests with a significance level of α=0·025. Findings Abnormal scans had a mean sensitivity of 77·7% for detecting clinical probable DLB, with specificity of 90·4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85·7% was achieved for overall diagnostic accuracy, 82·4% for positive predictive value, and 87·5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's κ=0·87). The procedure was well tolerated with few adverse events. Interpretation A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with123 I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.
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