Lipoprotein(a) and cognitive performances in an elderly white population: Cross-sectional and follow-up data

Background and Purpose - Elevated lipoprotein(a) [Lp(a)l serum levels have been associated with an increased risk of vascular diseases, and preliminary observations suggest that they are a risk factor for vascular dementia. The relationship between Lp(a) levels and cognitive performances in the general population has never been investigated. Our aim was to evaluate the effect of elevated Lp(a) levels on cognitive functions in the elderly, Methods - Cognitive performances were assessed by means of the Mini-Mental State Examination (MMSE), the Babcock Short Story, and the Matrix Test in a population sample of 435 white subjects aged 65 to 84 years who were evaluated at baseline and after 3 years. Lp(a) levels were determined by ELISA. Results - No statistically significant difference was found in neuropsychological test scores between subjects with and without elevated Lp(a) levels, although subjects with elevated Lp(a) levels had slightly better cognitive performances. This difference reached a statistical significance level only in a subscore of the Matrix Test (number of correct responses) when adjusted for age,:sex, education, smoking, and history of stroke; At follow-up, no statistically significant difference was found in cognitive performances between subjects with and without elevated Lp(a) serum levels in either univariate or multivariate analyses. Subjects with and without elevated Lp(a) showed a similar decline rate during follow-up. Conclusions In this sample of elderly white subjects, elevated Lp(a) levels were not associated with poorer cognitive performances or with an increased rate of cognitive decline. Elevated Lp(a) levels do not appear to be a major determinant of cognitive impairment in the elderly

Cognitive phenotypes and factors associated with cognitive decline in a cohort of older patients with atrial fibrillation: The Strat-AF study

Background and purpose: The multifactorial relationship between atrial fibrillation (AF) and cognitive impairment needs to be elucidated. The aim of this study was to assess, in AF patients on oral anticoagulants (OACs), the prevalence of cognitive impairment, defined according to clinical criteria or data-driven phenotypes, the prevalence of cognitive worsening, and factors associated with cognitive outcomes. Methods: The observational prospective Strat-AF study enrolled AF patients aged ≥ 65 years who were receiving OACs. The baseline and 18-month protocol included clinical, functional, and cognitive assessment, and brain magnetic resonance imaging. Cognitive outcomes were: empirically derived cognitive phenotypes; clinical diagnosis of cognitive impairment; and longitudinal cognitive worsening. Results: Out of 182 patients (mean age 77.7 ± 6.7 years, 63% males), 82 (45%) received a cognitive impairment diagnosis, which was associated with lower education level and functional status, and higher level of atrophy. Cluster analysis identified three cognitive profiles: dysexecutive (17%); amnestic (25%); and normal (58%). Compared to the normal group, the dysexecutive group was older, and had higher CHA2DS2-VASc scores, while the amnestic group had worse cognitive and functional abilities, and medial temporal lobe atrophy (MTA). Out of 128 followed-up patients, 35 (27%) had cognitive worsening that was associated with lower education level, worse cognitive efficiency, CHA2DS2-VASc score, timing of OAC intake, history of stroke, diabetes, non-lacunar infarcts, white matter hyperintensities and MTA. In multivariate models, belonging to the dysexecutive or amnestic group was a main predictor of cognitive worsening. Conclusions: In our cohort of older AF patients, CHA2DS2-VASc score, timing of OAC intake, and history of stroke influenced presence, type and progression of cognitive impairment. Empirically derived cognitive classification identified three groups with different clinical profiles and better predictive ability for cognitive worsening compared to conventional clinical diagnosis

Can CHA2DS2-VASc and HAS–BLED Foresee the Presence of Cerebral Microbleeds, Lacunar and Non-Lacunar Infarcts in Elderly Patients With Atrial Fibrillation? Data From Strat–AF Study

Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic risk. In this context, validity of congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke, vascular disease, age 65–74 years and sex category (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS–BLED) scales, used to respectively evaluate thrombotic and hemorrhagic risks, is incomplete. In patients with AF, brain MRI has led to the increased detection of “asymptomatic” brain changes, particularly those related to small vessel disease, which also represent the pathologic substrate of intracranial hemorrhage, and silent brain infarcts, which are considered risk factors for ischemic stroke. Routine brain MRI in asymptomatic patients with AF is not yet recommended. Our aim was to test predictive ability of risk stratification scales on the presence of cerebral microbleeds, lacunar, and non-lacunar infarcts in 170 elderly patients with AF on oral anticoagulants. Ad hoc developed R algorithms were used to evaluate CHA2DS2-VASc and HAS–BLED sensitivity and specificity on the prediction of cerebrovascular lesions: (1) Maintaining original items' weights; (2) augmenting weights' range; (3) adding cognitive, motor, and depressive scores. Accuracy was poor for each outcome considering both scales either in phase 1 or phase 2. Accuracy was never improved by the addition of cognitive scores. The addition of motor and depressive scores to CHA2DS2-VASc improved accuracy for non-lacunar infarcts (sensitivity = 0.70, specificity = 0.85), and sensitivity for lacunar–infarcts (sensitivity = 0.74, specificity = 0.61). Our results are a very first step toward the attempt to identify those elderly patients with AF who would benefit most from brain MRI in risk stratification

Mechanical thrombectomy in patients with proximal occlusions and low NIHSS: Results from a large prospective registry

Background: Mechanical thrombectomy is now standard of care for treatment of acute ischemic stroke secondary to large vessel occlusion in the setting of high NIHSS. We analysed a large nationwide registry focusing on patients with large vessel occlusion and low NIHSS on admission to evaluate the efficacy and safety of thrombectomy in this patient population Methods: 2826 patients treated with mechanical thrombectomy were included in a multicentre registry from January 1, 2011 to December 31, 2015. We included patients with large vessel occlusion and NIHSS ≤ 6 on admission. Baseline characteristics, imaging, clinical outcome, procedure adverse events and positive and negative outcome predictors were analysed. Results: 134 patients were included. 90/134 had an anterior circulation and 44 a posterior circulation stroke. One patient died before treatment. Successful revascularization (mTICI 2b-3) was achieved in 73.7% (98/133) of the patients. Intraprocedural adverse event was observed in 3% (4/133) of cases. Symptomatic intracranial haemorrhage rate was 5.3% (7/133). At three months, 70.9% (95/134) of the patients had mRS score 0-2, 15.7% (21/134) mRS 3-5 and 13.4% (18/134) mRS 6. Age and successful recanalization were significant predictors of a good clinical outcome on both univariate (p= 0.005 and p=0.007) and multivariable (p=0.0018 and p=0.009 [nat log]) analysis. Absence of vessel recanalization and symptomatic intracranial hemorrhage were independent predictors of poor outcome (p=0.021). Conclusions: Our study suggests that patients with large vessel occlusion and low NIHSS score on admission can benefit from mechanical thrombectomy. Randomized trials are warranted

Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All data will be made available upon request. Source data are provided with this paper.Code availability: All custom code has been written in ImageJ and MatLab and it is available at https://github.com/GabNar/Pracucci_Graham_Alberio_Nardi_et_al_2023.Cortical activity patterns are strongly modulated by fast synaptic inhibition mediated through ionotropic, chloride-conducting receptors. Consequently, chloride homeostasis is ideally placed to regulate activity. We therefore investigated the stability of baseline [Cl-]i in adult mouse neocortex, using in vivo two-photon imaging. We found a two-fold increase in baseline [Cl-]i in layer 2/3 pyramidal neurons, from day to night, with marked effects upon both physiological cortical processing and seizure susceptibility. Importantly, the night-time activity can be converted to the day-time pattern by local inhibition of NKCC1, while inhibition of KCC2 converts day-time [Cl-]i towards night-time levels. Changes in the surface expression and phosphorylation of the cation-chloride cotransporters, NKCC1 and KCC2, matched these pharmacological effects. When we extended the dark period by 4 h, mice remained active, but [Cl-]i was modulated as for animals in normal light cycles. Our data thus demonstrate a daily [Cl-]i modulation with complex effects on cortical excitability.TelethonRegione ToscanaRoyal SocietyBiotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council (MRC)Epilepsy Research UKNewcastle UniversityScuola Normale Superior

Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS

Combined intravenous and endovascular treatment versus primary mechanical thrombectomy. The Italian Registry of Endovascular Treatment in Acute Stroke

Background: Whether mechanical thrombectomy alone may achieve better or at least equal clinical outcome than mechanical thrombectomy combined with intravenous thrombolysis is a matter of debate. Methods: From the Italian Registry of Endovascular Stroke Treatment, we extracted all cases treated with intravenous thrombolysis followed by mechanical thrombectomy or with primary mechanical thrombectomy for anterior circulation stroke due to proximal vessel occlusion. We included only patients who would have qualified for intravenous thrombolysis. We compared outcomes of the two groups by using multivariate regression analysis and propensity score method. Results: We included 1148 patients, treated with combined intravenous thrombolysis and mechanical thrombectomy therapy (n = 635; 55.3%), or with mechanical thrombectomy alone (n = 513; 44.7%). Demographic and baseline clinical characteristics did not differ between the two groups, except for a shorter onset to groin puncture time (p < 0.05) in the mechanical thrombectomy group. A shift in the 90-day modified Rankin Scale distributions toward a better outcome was found in favor of the combined treatment (adjusted common odds ratio = 1.3; 95% confidence interval: 1.04–1.66). Multivariate analyses on binary outcome show that subjects who underwent combined treatment had higher probability to survive with modified Rankin Scale 0–3 (odds ratio = 1.42; 95% confidence interval: 1.04–1.95) and lower case fatality rate (odds ratio = 0.6; 95% confidence interval: 0.44–0.9). Hemorrhagic transformation did not differ between the two groups. Conclusion: These data seem to indicate that combined intravenous thrombolysis and mechanical thrombectomy could be associated with lower probability of death or severe dependency after three months from stroke due to large vessel occlusion, supporting the current guidelines of treating eligible patients with intravenous thrombolysis before mechanical thrombectomy