Mild cognitive impairment etiologic subtyping using pragmatic and conventional criteria: preliminary experience in the Florence VAS-COG clinic.

BACKGROUND: Mild cognitive impairment (MCI) is an abnormal condition defined by the presence of cognitive decline not severe enough to fit dementia criteria. According to Winblad et al.'s criteria, the clinical distinction of MCI subtypes (amnestic/non-amnestic, single/multiple domain) is based on the cognitive profiling (conventional diagnosis) and infers possible different MCI etiologies. MCI prodromic of vascular dementia (Vasc-MCI) is thought to be characterized by a multiple domain profile. In our outpatient clinic (the "Florence VAS-COG clinic"), the diagnosis of MCI and of its different subtypes (vascular, degenerative, mixed) is based on a comprehensive evaluation of clinical and neuroimaging features (pragmatic diagnosis). AIMS: To compare the pragmatic and conventional diagnoses in terms of etiologic subtyping of MCI. METHODS: We retrospectively assessed the agreement between the two diagnoses in 30 MCI patients. Agreement was considered present when degenerative MCI was of the amnestic type (single or multiple domain) and Vasc-MCI was of the multiple domain type (amnestic or non-amnestic MCI). RESULTS: In 15/30 (50 %) patients, the diagnoses were in disagreement: 5/9 (56 %) patients diagnosed with a degenerative MCI type presented a non-amnestic cognitive profile (4 single domain and 1 multiple domain); 10/21 (48 %) Vasc-MCI were classified as non-amnestic single domain. CONCLUSIONS: The application of MCI etiologic subtyping using pragmatic or conventional diagnoses leads to different results. In our setting, not all the Vasc-MCI patients have a multiple domain profile. Our preliminary study suggests that the cognitive profile of Vasc-MCI is more heterogeneous than previously suggested.

Influence of vascular risk factors and neuropsychological profile on functional performances in CADASIL: results from the MIcrovascular LEukoencephalopathy Study (MILES).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. METHODS: In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). RESULTS: We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥ 2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (ß = -0.418, P < 0.003) in CADASIL patients and the executive function index (ß = -0.321, P = 0.028) in ARL. CONCLUSIONS: This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.

The Luigi Sacco Hospital VAS-COG stroke care pathway: A five-year experience.

Background: Psycho-cognitive consequences are a frequent cause of disability in stroke survivors but are often underdiagnosed also because of lack of services dedicated to these aspects. We started assessing systematically cognitive and behavioral functions in acute stroke patients and to follow them up. Here, we report a retrospective analysis of the organization of the Sacco VAS-COG stroke care pathway and the refinements implemented during 5 years of activity. Methods: The protocol includes baseline collection of clinical history, general and neurologic examinations, functional, neuropsychological, and neuroimaging assessment. At follow-up, a diagnosis of cognitive decline was made based on best clinical judgment in the first period (January 2018 to May 2019, namely VAS-COG protocol 1.0) and then based on an extensive neuropsychological battery (May 2019 to January 2023, namely VASCOG protocol 2.0); psychiatric and behavioral disturbances are investigated through suitable scales. Results: From January 2018 to December 2022, 834 patients (mean age 76±13.6 years; 46.6 % females) with acute cerebrovascular events were admitted to the stroke unit, mostly (80 %) for ischemic strokes. Pre-event cognitive impairment was not assessable in 78 patients (9.3 %) because no reliable informant was present and was reported in 327/756 (43 %) patients. During follow-up, post-stroke cognitive impairment was detected in 124/217 (57.1 %) patients in VAS-COG protocol 1.0 and in 137/201(68.2 %) patients in VAS-COG protocol 2.0, while 95/218 (43.2 %) patients were found to be depressed and patients presented on average 2.5 neuropsychiatric symptoms on Neuropsychiatric Inventory-questionnaire. Conclusions: The VAS-COG stroke care pathway represents a model for patients and for their families.

Assessing the Nature of Chiral-Induced Spin Selectivity by Magnetic Resonance.

Understanding chiral-induced spin selectivity (CISS), resulting from charge transport through helical systems, has recently inspired many experimental and theoretical efforts but is still the object of intense debate. In order to assess the nature of CISS, we propose to focus on electron-transfer processes occurring at the single-molecule level. We design simple magnetic resonance experiments, exploiting a qubit as a highly sensitive and coherent magnetic sensor, to provide clear signatures of the acceptor polarization. Moreover, we show that information could even be obtained from time-resolved electron paramagnetic resonance experiments on a randomly oriented solution of molecules. The proposed experiments will unveil the role of chiral linkers in electron transfer and could also be exploited for quantum computing applications.

Self-perceived memory impairment and cognitive performance in an elderly independent population with age-related white matter changes.

OBJECTIVES: To determine whether self-perceived memory impairment is associated with the severity of white matter changes (WMC) and is related to cognitive impairment. METHODS: Data were drawn from the multinational Leukoaraiosis and Disability Study (LADIS), which investigates the impact of WMC on global functioning. WMC severity was rated using the Fazekas scale. Medial temporal lobe atrophy (MTA) was scored visually and mean values were calculated. The neuropsychological battery consisted of the Mini-Mental State Examination, a modified version of the VADAS-Cog, Trail making and Stroop tests. A question about self-perceived memory impairment was used as a measure for presence of memory complaints. Cognitive performance was analysed test-by-test and in three main domains: memory, executive functions and speed/motor control. The Geriatric Depression Scale (GDS) was used as a measure of depressive symptoms. RESULTS: Six hundred and thirty-eight subjects were included in this study. No association was found between memory complaints and the severity of WMC. Subjects with memory complaints (n = 399) had a higher GDS score [t((637)) = -7.15; p<0.02] and performed worse on almost all cognitive tests and on the three cognitive domains. Multiple linear regression showed that the worse performance on the memory domain was associated with memory complaints independently of depressive symptoms, WMC severity and MTA (R(2) = 0.183; F = 17.09, beta = -0.126; p<0.05). CONCLUSION: In a sample of non-disabled elderly subjects with WMC, self-perceived memory impairment is significantly associated with objective memory impairment independently of the WMC severity, depressive symptoms and MTA.

Whole-brain histogram and voxel-based analyses of diffusion tensor imaging in patients with leukoaraiosis: correlation with motor and cognitive impairment.

BACKGROUND AND PURPOSE: Cerebral white matter changes, termed leukoaraiosis (LA), appearing as areas of increased signal intensity in T2-weighted MR images, are common in elderly subjects, but the possible correlation of LA with cognitive or motor deficit has not been established. We hypothesized that histogram and voxel-based analyses of whole-brain mean diffusivity (MD) and fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) could be more sensitive tools than visual scales to investigate the clinical correlates of LA. MATERIALS AND METHODS: Thirty-six patients of the Leukoaraiosis and Disability Study were evaluated with fluid-attenuated inversion recovery for LA extension, T1-weighted images for volume, and DTI for MD and FA. The extent of LA was rated visually. The normalized total, gray, and white matter brain volumes were computed, as well as the 25th percentile, 50th percentile, kurtosis, and skewness of the MD and FA maps of the whole brain. Finally, voxel-based analysis on the maps of gray and white matter volume, MD, and FA was performed with SPM2 software. Correlation analyses between visual or computerized data and motor or neuropsychologic scale scores were performed using the Spearman rank test and the SPM2 software. RESULTS: The visual score correlated with some MD and FA histogram metrics (P<.01). However, only the 25th and 50th percentiles, kurtosis, and skewness of the MD and FA histograms correlated with motor or neuropsychologic deficits. Voxel-based analysis revealed a correlation (P<.05 corrected for multiple comparisons) between a large cluster of increased MD in the corpus callosum and pericallosal white matter and motor deficit. CONCLUSIONS: These results are consistent with the hypothesis that histogram and voxel-based analyses of the whole-brain MD and FA maps are more sensitive tools than the visual evaluation for clinical correlation in patients with LA.

Rapidly progressive cognitive impairment in a patient with high flow dural arteriovenous fistulas, cerebral sinus thrombosis and protein S deficiency.

Dural arteriovenous fistula (DAVF) may present with a variety of neurological symptoms, ranging from tinnitus to fatal hemorrhage. We report a case of rapidly progressive cognitive impairment due to cerebral venous engorgement that reversed after endovascular treatment in a patient with DAVF, cerebral sinus thrombosis and protein S deficiency. DAVF may be a cause of vascular cognitive impairment and should be considered particularly in cases with a rapidly progressive course because they are potentially treatable.

Fully automated solid-phase microextraction-fast gas chromatography-mass spectrometry method using a new ionic liquid column for high-throughput analysis of sarcosine and N-ethylglycine in human urine and urinary sediments.

A fully automated, non invasive, rapid and high-throughput method for the direct determination of sarcosine and N-ethylglycine in urine and urinary sediments using hexyl chloroformate derivatization followed by direct immersion solid-phase micro extraction and fast gas chromatography-mass spectrometric analysis was developed and validated. The use of a new ionic liquid narrow bore column, as well as the automation and miniaturization of the preparation procedure by a customized configuration of the utilized XYZ robotic system, allowed a friendly use of the GC apparatus achieving a quantitation limit of 0.06 µg L(-1) for sarcosine, good repeatability with CV always lower than 7% and reduced analysis times useful for point-of-care testing. The method was then applied for the analysis of 56 samples of urine and urinary sediments in healthy subjects, in those with benign prostatic hypertrophy and in patients with clinically localized prostate cancer. The results obtained showed that the medians of sarcosine/creatinine in urine were 103, 137 and 267 µg g(-1) respectively, thus assessing the potential use of sarcosine as urinary biomarker for prostate cancer detection. The highest values of sensitivity (79%) and specificity (87%) were obtained in correspondence of a cut-off value of 179 µg sarcosine(g creatinine)(-1), thus by using this cut-off threshold, sarcosine was significantly associated with the presence of cancer (p<0.0001). Finally, ROC analyses proved that the discrimination between clinically localized prostate cancer and patients without evidence of tumor is significantly correlated with sarcosine.

Occurrence of diffuse, poorly differentiated hepatocellular carcinoma during pegylated interferon plus ribavirin combination therapy for chronic hepatitis C.

Interferon therapy is indicated for the treatment of chronic hepatitis C and prevention of hepatocellular carcinoma. We describe the case of a 66-year-old Italian woman who received pegylated interferon alpha-2a plus ribavirin combined therapy for HCV-related chronic liver disease. Preliminary hematochemical, ultrasound and bioptic investigations did not show liver cirrhosis or hepatocarcinoma. After 24 weeks of treatment transaminase serum levels were in the normal range and circulating HCVRNA was undetectable by PCR qualitative assay. On week 46 a serious adverse event occurred, with rapid transaminase increase, severe hyperpyrexia, and abdominal pain, leading to interruption of interferon and ribavirin. Liver biopsy was repeated and it revealed poorly differentiated hepatocellular carcinoma. Only palliative care could be performed and the patient died of liver failure within 2 months. The present case underlines that hepatocellular carcinoma can be misdiagnosed in spite of laboratory and instrumental follow-up. More sensitive tools are needed for tumor detection, to avoid IFN impairment of the liver, even though it eradicates HCV.