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Background and purpose Alzheimer's disease (AD) is considered a clinical and biological continuum identified via cerebrospinal fluid (CSF) or imaging biomarkers. Chronic hypoperfusion is held as one of the main features of Alzheimer's disease, as part of the processes causing neuronal degeneration. The mechanism responsible for such condition is still debated, although recently a direct connection with amyloid peptides has been shown. Here the aim was to investigate whether measures of hypoperfusion change along the AD continuum. Methods Seventy patients with mild AD were recruited and stratified according to their CSF biomarker profile—as indicated by the National Institute on Aging and Alzheimer’s Association research framework—into patients with either isolated amyloid pathology (A+T−) or full‐blown AD (A+T+), and further layered according to apolipoprotein E genotype. After evaluation of vascular risk factors, a transcranial Doppler was performed on each patient, to evaluate mean flow velocity and pulsatility index in the middle cerebral artery, and to calculate the breath‐holding index. Patients were compared to a cohort of 17 healthy controls. Results The breath‐holding index was reduced in the AD continuum and was inversely correlated to CSF amyloid β42 levels. Such correlation was stronger in the A+T+ than in the A+T− group, and unexpectedly reached statistical significance only in the E3 and not in the E4 genotype carriers. Conclusions These results suggest a tight and effective relationship between amyloid β42, vascular hypoperfusion, cerebrovascular reactivity and epsilon genotype.

Background The use of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients has increased with a parallel burden in procedural costs. We tested whether a new prognostic score could identify patients who are unlikely to benefit from MT. Methods Patients from our endovascular stroke registry were assessed for imaging and clinical outcome measures and randomly divided into two subsets for derivation and validation. We created a new prognostic score based on clinical and radiological prognostic factors of poor outcome (mRS score ≥ 3) from the derivation cohort. Receiver operating characteristics curve analysis was used to assess the discrimination ability of the score. The score was then validated and compared to the MR PREDICTS score. Results The derivation/validation included 270/116 patients, respectively. After multivariate logistic regression analysis, pre stroke mRS, age, admission glycaemia, admission NIHSS, collateral flow, Clot Burden Score, Alberta Stroke Program Early CT score were used to create a new prognostic scoring system called Tor Vergata Stroke Score (TVSS). TVSS revealed a good prognostic accuracy with an AUC of 0.825 [95% CI 0.77-0.88] in the derivation cohort and an AUC of 0.820 [95% CI 0.74-0.90] in the validation cohort. When compared to the MR PREDICTS in the validation cohort, TVSS demonstrated higher prediction ability which was, however, not statistically significant (0.80 vs 0.78; P = 0.26). Conclusions TVSS is a reliable tool for selection of AIS candidates for MT and optimization of transfer to comprehensive stroke centers.

Purpose Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion. Methods A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3-month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated. Results Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome. Conclusion Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3-month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome. Keywords Circle of Willis • Large vessel occlusion • Stroke severity • Endovascular treatment • OutcomeAvailability of data and material Data supporting the findings of this study are available upon reasonable request

Objective This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage. Methods We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia. Results The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3–35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32–3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13–2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01–2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00–2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60–2.87). Conclusion Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up.