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Cerebral amyloid angiopathy (CAA) is recognized as a cause of cognitive impairment, but its cognitive profile needs to be characterized, also respect to hypertension-related microangiopathy (HA). We aimed at comparing difference or similarity of CAA and HA patients’ cognitive profiles, and their associated factors. Participants underwent an extensive clinical, neuropsychological, and neuroimaging protocol. HA patients (n = 39) were more frequently males, with history of vascular risk factors than CAA (n = 32). Compared to HA, CAA patients presented worse performance at MoCA (p = 0.001) and semantic fluency (p = 0.043), and a higher prevalence of amnestic MCI (46% vs. 68%). In univariate analyses, multi-domain MCI was associated with worse performance at MoCA, Rey Auditory Verbal Learning Test (RAVLT), and semantic fluency in CAA patients, and with worse performance at Symbol Digit Modalities Test (SDMT) and phonemic fluency in HA ones. In multivariate models, multi-domain deficit remained as the only factor associated with RAVLT (β = − 0.574) in CAA, while with SDMT (β = − 0.364) and phonemic fluency (β = − 0.351) in HA. Our results highlight different patterns of cognitive deficits in CAA or HA patients. While HA patients’ cognitive profile was confirmed as mainly attentional/executive, a complex cognitive profile, characterized also by deficit in semantic memory, seems the hallmark of CAA patients.

Post-stroke cognitive impairment (PSCI) includes all forms of cognitive decline that develop after stroke, even if not severe enough to fit the criteria of dementia. Our aims were to investigate the predictive value of a brief bedside examination (Montreal Cognitive Assessment, MoCA) in the acute phase of stroke on the diagnosis of mid-term PSCI, taking into account other clinical, cognitive, functional, and neuroimaging predictors. Consecutive patients admitted to a stroke unit were evaluated with MoCA between 5 and 9 days after stroke. At baseline, clinical, functional, and neuroimaging data were collected. Patients were reassessed between 6 and 9 months after stroke by means of an extensive neuropsychological and functional evaluation. Out of 137 enrolled stroke patients, 80 (58.4 %) were followed up (mean age 68.2 ± 14.6 years, males 66 %, mean NIHSS score 3.6 ± 4.8). PSCI was diagnosed in 47 patients (59 %; 35 mild cognitive impairment, 12 dementia). Controlling for age, education, functional and cognitive pre-morbid status, stroke severity, and pre-existing lacunar infarcts, MoCA baseline score [OR (95 % CI) = 1.4(1.1–1.8)] for each point] and leukoaraiosis severity [OR (95 % CI) = 0.4(0.2–0.9)] for each point of the van Swieten scale] were independently associated with PSCI. Using a ROC analysis, a cut-off of 21 predicted the diagnosis of PSCI with 91.4 % sensitivity, 75.8 % specificity, 80 % positive predictive value, and 89.3 % negative predictive value. In a sample of mild stroke patients, MoCA seems to be a good predictor of mid-term PSCI, making it a possible candidate for a brief cognitive screening in the acute stroke setting.

Comparison studies on recovery outcomes in ischemic (IS) and hemorrhagic strokes (HS) have yielded mixed results. In this retrospective observational study of consecutive IS and HS patients, we aimed at evaluating functional outcomes at discharge from an intensive rehabilitation hospital, comparing IS vs. HS, analyzing possible predictors. Modified Rankin Scale (mRS) at discharge was the main outcome. Out of the 229 patients included (mean age 72.9 ± 13.9 years, 48% males), 81 had HS (35%). Compared with IS (n = 148), HS patients were significantly younger (75 ± 12.5 vs. 68.8 ± 15.4 years, p = 0.002), required longer hospitalizations both in acute (23.9 ± 36.7 vs. 35.2 ± 29.9 days, p = 0.019) and rehabilitation hospitals (41.5 ± 31.8 vs. 77.2 ± 51.6 days, p = 0.001), and had more severe initial clinical deficit (mean number of neurological impairments: 2.0 ± 1.1 vs. 2.6 ± 1.4, p = 0.001) and mRS scores at admission (p = 0.046). At discharge, functional status change, expressed as mRS, was not significantly different between IS and HS (F = 0.01, p = 0.902), nor was the discharge destination (p = 0.428). Age and clinical severity were predictors of functional outcome in both stroke types. On admission in an intensive rehabilitation hospital, HS patients presented a worse functional and clinical status compared to IS. Despite this initial gap, the two stroke types showed an overlapped trajectory of functional recovery, with age and initial stroke severity as the main prognostic factors.

The relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T hyperintensities in the cerebral WM, also known as leukoaraiosis. Sixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria. We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T hyperintensities, and diffusion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model. After 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia. Our findings confirm the complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features.

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease responsible for recurrent ischemic strokes, often with a progressive course leading to dementia and disability. On MRI, lacunes, microbleeds, and severe white matter alterations are typical features of the disease. In case of acute stroke, because of the bleeding risk associated with the disease and the doubtful efficacy of fibrinolytic treatment in a disease with poor evidence of thrombosis, the efficacy of intravenous thrombolysis remains unproven. Nevertheless, stroke is a frequent occurrence in CADASIL patients, and clinicians not unlikely may face in the emergency room the situation of a CADASIL patient with an acute stroke within the time window for thrombolysis.ObjectiveWe report on two CADASIL patients treated with intravenous alteplase for acute ischemic stroke, and we present a review of literature aimed to report epidemiological data, efficacy and safety of intravenous thrombolysis in CADASIL patients.MethodsWe performed a systematic review of medical literature published until August 2, 2022. Case reports and series in English language reporting on CADASIL patients and acute stroke were included.ResultsBoth patients were treated with intravenous thrombolysis without complications and had a good clinical outcome. The systematic review identified three case reports of CADASIL patients who were treated with intravenous alteplase for acute ischemic stroke; no bleedings complications were described.ConclusionsAvailable data on intravenous thrombolysis in CADASIL patients are scarce but suggest that this treatment can be taken into consideration for these patients.

Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear. To investigate the relationship between baseline and incident depression and progression of white matter changes. In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale. Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline. Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.

Background: Atrial fibrillation (AF) is one of the most common heart rhythm disorders encountered in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF, but certain questions still remain unanswered, in particular whether AF-related inflammation is a cause or a consequence of the arrhythmia, and whether inflammation reflects underlying disease or AF itself. At the current state of the art, scientific evidence on the role of oral anticoagulants (OAC) in modulating pro-inflammatory cytokines implicated in the pathogenesis of AF remains scarce. The aim of our study was to evaluate, in a population of AF patients undergoing OAC, the different roles of anticoagulant therapy [Vitamin K antagonists (VKAs) and direct oral anti-coagulants (DOACs)] in modulating the levels of inflammatory biomarkers in AF. Methods: The Strat-AF study is an observational, prospective, single center, hospital-based study enrolling elderly patients with AF. Results refer to 170 subjects with complete clinical and biohumoral assessment. Results: At multivariate logistic regression analysis, adjusted for several covariates, VKA treatment was an independent protective predictor for having a high grade of inflammation not balanced by anti-inflammatory cytokine levels [OR = 0.26 (0.10–0.69), p = 0.007]. Conclusions: These results from the Strat-AF study are “generators of hypotheses” and provide preliminary evidence for the differential effects of VKAs and DOACs on inflammatory biomarkers (e.g., IL-6, TNF-α) in AF patients. These findings suggest that inflammatory biomarkers could enhance stroke risk prediction models, potentially improving a tailored AF management.

Background: Cerebrovascular diseases (CVDs) are considered the second most common cause of cognitive decline in the elderly after neurodegeneration of the Alzheimer’s type. Despite impressive epidemiological data, the actual burden of CVDs in terms of cognitive decline is still incompletely appreciated by physicians and health regulators. Methods: In this brief position paper, we review some evidence related to the topic and its clinical relevance, and we present some concepts that we consider of crucial importance for the correct recognition of the problem. Results and Conclusions: We conclude that: (1) different approaches to the topic exist (clinical, neuroimaging-based, pathological) and the inconsistent use of one or another, together with lack of definitions, has limited the appreciation of the contribution of CVDs to cognitive decline; (2) cognitive impairment related to CVDs is very frequent and constitutes a topic with high epidemiological impact; (3) cognitive impairment associated with CVDs is heterogeneous in clinical and pathogenic terms; (4) vascular lesions often interact with other type lesions, the most important of which are today considered those of the Alzheimer’s type, in determining cognitive impairment; (5) for some vascular lesions, namely white matter lesions and lacunar infarcts, strong evidence suggests their role as determinants of cognitive decline; (6) cognitive impairment is only part of the consequences of CVDs as it is almost invariably accompanied by gait disturbances, depressive symptoms, and sphincteric control dysfunction, all factors contributing to loss of independence.

Objectives This study aims to evaluate the diagnostic performance of NIHSS extinction and inattention item, compared to the results of the Oxford Cognitive Screen (OCS) heart subtest. Additionally, the possible role of the NIHSS visual field subtest on the NIHSS extinction and inattention subtest performance is explored and discussed. Methods We analysed scores on NIHSS extinction and inattention subtest, NIHSS visual field subtest, and OCS heart subtest on a sample of 118 post-stroke patients. Results Compared to OCS heart subtest, the results on NIHSS extinction and inattention subtest showed an accuracy of 72.9% and a moderate agreement level (Cohen’s kappa = 0.404). Furthermore, a decrease in NIHSS accuracy detecting neglect (61.1%) was observed in patients with pathological scores in NIHSS visual field item. Conclusions Extreme caution is recommended for the diagnostic performance of extinction and inattention item of NIHSS. Signs of neglect may not be detected by NIHSS, and may be confused with visual field impairment. Trial registration This study refers to an observational study protocol submitted to ClinicalTrials.gov with identifier: NCT03968627 . The name of the registry is “Development of a National Protocol for Stroke Rehabilitation in a Multicenter Italian Institution” and the date of the registration is the 30th May 2019.