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Background Cerebral 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. Objective We 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. Methods We 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. Results Both 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. Conclusions Available data on intravenous thrombolysis in CADASIL patients are scarce but suggest that this treatment can be taken into consideration for these patients.

We aimed to identify features associated with different disease trajectories in Alzheimer's disease (AD)-related primary progressive aphasia (PPA). We considered 23 patients diagnosed with AD-related PPA. All patients underwent neuropsychological evaluation

BackgroundWe aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer’s disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).MethodsThis longitudinal cohort study involved 140 patients (50 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (CSF, amyloid-PET, and18F-FDG-PET) at baseline. They were rated according to the A/T/N system and followed up for a mean time of 2.72±0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements after two years after baseline.ResultsAt baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N-) with high accuracy (AUC=0.82). We identified cut-off value of19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (p-SCD), and 14 MCI patients developed AD dementia (p-MCI). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% C.I.=65.69:94.31]). The rate of NfL change was higher in p-MCI (3.52±4.06 pg/mL) compared to np-SCD (0.81±1.25 pg/mL) and np-MCI (−0.13±3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC=0.954).ConclusionPlasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease.Key messagesWhat is already known on this topicPlasma NfL increase in SCD, MCI and AD and longitudinal changes in NfL are related to changes in brain atrophy and cognitive outcomes in AD. Nevertheless, the clinical value of plasma NfL in non-demented patients has been poorly explored.What this study addsPlasma NfL accurately predicts AD pathology and progression of cognitive decline in SCD and MCI. Repeated measurements of NfL may further increase the accuracy of this biomarkerHow this study might affect research, practice, or policyGiven its accessibility, blood-based NfL can assist clinicians in determining the optimal personalized diagnostic and therapeutic approach for individuals presenting with SCD or MCI, providing insights into the underlying biological mechanisms of cognitive decline, even in primary care settings.

Introduction Neurofilament light chain (NfL) is becoming increasingly notable in neurological diseases including AD, and it has been suggested as a new peripherical biomarker of neurodegeneration. We aimed to compare plasma NfL levels among Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI), and AD patients and to evaluate relationships between NfL and CSF biomarkers and neuropsychological scores. Materials and methods We enrolled 110 patients (34 SCD, 53 MCI, and 23 AD), who underwent clinical and neuropsychological evaluation, APOE genotyping, and plasma NfL analysis. Ninety-one patients underwent at least one amyloid burden biomarker (CSF and/or amyloid PET); 86 patients also underwent CSF phosphorylated-tau (p-tau) and total-tau (t-tau) measurement. Patients were classified as A + if they presented at least one positive amyloid biomarker or A− if not. Results NfL levels were significantly increased in AD and MCI compared to SCD patients. These differences depend on A status, e.g., SCD A + had lower NfLs than MCI A + but comparable with MCI A−. Similarly, MCI A + had higher NfL levels than MCI A−, but comparable with AD. NfL levels correlated with p-tau in SCD, with all CSF biomarkers in MCI patients. No correlations were found in AD subgroup. In SCD, NfL levels were negatively correlated with memory test scores. Conclusions Plasma NfL levels might be a promising biomarker for neurodegeneration to discriminate cognitive decline due to AD from other conditions causing cognitive impairment in prodromal stages. Considering correlations with CSF p-tau and memory tests in SCD, NfL might be a useful peripheral biomarker also in preclinical phases of AD.

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called “spice of life”, in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer’s Diseases, Parkinson’s Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.

Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ42 levels, comparable with Alzheimer’s Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ42, Aβ42/Aβ40, p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ42 levels were not different between iNPH and AD, while Aβ42/Aβ40, p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ42/Aβ40 was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ42/Aβ40 had higher p-tau and t-tau than iNPH patients with negative Aβ42/Aβ40. Those iNPH patients who showed cognitive impairment had lower Aβ42/Aβ40 and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ42 with negative Aβ42/Aβ40, p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ42/Aβ40 in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.

Huntingtin (HTT) is a gene containing a key region of CAG repeats. HTT alleles containing from 27 to 35 CAG repeats are termed intermediate alleles (IAs). We aimed to assess the effect of IAs on progression of cognitive impairment in patients with subjective cognitive decline (SCD).We included 106 patients with SCD. All the patients underwent neuropsychological assessments and blood sample collection at baseline. Patients were followed up for a median (interquartile range) time of 13.75 (8.17) years. We genotyped APOE and HTT at the end of the follow-up.Eleven out of 106 patients (10.38%, 95% confidence interval [CI] 4.57-16.18) were carriers of IAs (IAIntermediate alleles interact with age and APOE ɛ4, increasing the risk of progression to MCI in SCD patients.

Empathy is the ability to understand (cognitive empathy) and to feel (affective empathy) what others feel. The aim of the study was to assess empathy deficit and neuronal correlates in Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) dementia. Twenty-four SCD, 41 MCI and 46 CE patients were included. Informer-rated Interpersonal Reactivity Index was used to explore cognitive (Perspective Taking-PT, Fantasy-FT) and affective (Empathic Concern-EC, Personal Distress-PD) empathy, before (T0) and after (T1) cognitive symptoms' onset. Emotion recognition ability was tested through Ekman-60 Faces Test. Cerebral FDG-PET SPM analysis was used to explore neural correlates underlying empathy deficits. FT-T1 scores were lower in AD compared to SCD (13.0 ± 8.0 vs 19.1 ± 4,7 p = 0.008), PD-T1 score were higher in AD compared to MCI and to SCD (27.00 ± 10.00 vs 25.3 ± 5.9 vs 20.5 ± 5.6, p = 0.001). A positive correlation was found between PT-T1 and metabolic disfunction of right middle gyrus (MFG) in MCI and AD. In AD group, a positive correlation between PT-T1 and insula and superior temporal gyrus (STG) metabolism was detected. A negative correlation was found between PD-T1 and superior parietal lobule metabolism in MCI, and between PD-T1 and STG metabolism in AD. Impairment of cognitive empathy starts at MCI stage. Increase of PD starts from preclinical phases and seems to be to be dissociated from cognitive decline. Loss of PT is related to a progressive involvement starting from right MFG in prodromal stage, extending to insula and STG in dementia. Heightened emotional contagion is probably related to derangement of mirror neurons systems in parietal regions in prodromal stages, and to impairment of temporal emotion inhibition system in advanced phases. Further studies are needed to clarify if alterations in emotional contagion might be a predictive feature of a cognitive decline driven by AD.