Sandro Marini

Do cholinesterase inhibitors act primarily on attention deficit? A naturalistic study in Alzheimer's disease patients.

Attention is the first non-memory domain affected in Alzheimers disease (AD), before deficits in language and visuo-spatial function, and it is claimed that attention deficits are responsible for the difficulties with daily living in early demented patients. The aim of this longitudinal study in a group of 121 Caucasian, community-dwelling, mild-to-moderate AD patients (Mini-Mental State Examination (MMSE) score >17) was to detect which cognitive domains were most affected by the disease and whether one year treatment with cholinesterase inhibitors was more effective in preserving attention than memory. All subjects were evaluated by a neuropsychological battery including global measurements (MMSE, Information-Memory-Concentration Test) and tasks exploring verbal long-term memory, language, attention, and executive functions. The comparison between two evaluations, made 12 months apart, shows statistically significant differences, indicating deterioration compared to baseline, in the following tests: MMSE (with no gender differences), Composite Memory Score, Short Story Delayed Recall, Trail-Making Test A, Semantic Fluency Test, and Token Test. Conversely, there were no differences in the two evaluations of the Digit Span, Corsi Tapping Test, Short Story Immediate Recall, and Phonemic Fluency Tests. It appears that the treatment specifically attenuated the decline in tests assessing attention and executive functions. A stabilization of the ability to pay attention, with the ensuing positive effects on executive functions, recent memory, and information acquisition which depend on attention, appears to be the main neuropsychological mechanism through which the activation of the cholinergic system, resulting from cholinesterase inhibition, exerts its effect on cognition.

White matter microstructural damage in small vessel disease is associated with montreal cognitive assessment but not with mini mental state examination performances: Vascular mild cognitive impairment tuscany study

Background and Purpose— Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment. Diffusion tensor imaging is sensitive to white matter microstructural damage. We investigated if diffusion tensor imaging-derived indices are more strongly associated with performances on MoCA or on the widely used mini mental state examination in patients with mild cognitive impairment and small vessel disease. Methods— Mild cognitive impairment patients with moderate/severe degrees of white matter hyperintensities on MRI were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy and median values of mean diffusivity and fractional anisotropy of the cerebral white matter were studied and correlated with cognitive tests performances. Results— Seventy-six patients (mean age 75.1±6.8 years, mean years of education 8.0±4.3) were assessed. In univariate analyses, a significant association of both MoCA and mini mental state examination scores with age, education, cortical atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and fractional anisotropy were associated with MoCA. In partial correlation analyses, adjusting for all demographic and neuroimaging variables, both mean diffusivity and fractional anisotropy were associated only with MoCA (mean diffusivity: r= −0.275, P=0.023; fractional anisotropy: r=0.246, P=0.043). Conclusions— In patients with mild cognitive impairment and small vessel disease, diffusion tensor imaging-measured white matter microstructural damage is more related to MoCA than mini mental state examination performances. MoCA is suited for the cognitive screening of patients with small vessel disease.

Operationalizing mild cognitive impairment criteria in small vessel disease: The VMCI-Tuscany Study

Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile.

Implication of serotonin-transporter (5-HTT) gene polymorphism in subjective memory complaints and mild cognitive impairment (MCI).

Serotonin-transporter-linked polymorphism (5-HTTLPR) is involved in neuropsychiatric diseases and recently the S-isoform has been correlated with a higher risk of developing emotion-induced retrograde amnesia. In order to better clarify the possible role of the 5-HTT S/L polymorphism and its effects on cognitive ability, especially on memory skills, we report here the distributions of the 5-HTT genetic variant and the Apolipoprotein E (ApoE) ɛ-4 allele and their association with neuropsychological measures in older adults reporting problems with everyday memory. Moreover, we verified the presence of a possible association between the S-allele with depression and the personal trait of neuroticism. Our results indicate an association between the 5-HTTLPR S-allele and the risk of developing MCI. No association was found in the other three groups. We found a positive dose-dependent association between the S-allele and the Rey-Osterrieth complex figure test (recall) score. Finally, our data did not find an association between the same allele and depression or neuroticism. This data, in our opinion shows a slight, non-established influence of 5-HTTLPR on memory skills exhibited in challenging memory tests but no influence on other extra-mnesic cognitive abilities.

Cerebral microbleeds in patients with mild cognitive impairment and small vessel disease: The Vascular Mild Cognitive Impairment (VMCI)-Tuscany study

BACKGROUND AND OBJECTIVESnCerebral microbleeds (CMBs) are a neuroimaging expression of small vessel disease (SVD). We investigated in a cohort of SVD patients with mild cognitive impairment (MCI): 1) the reliability of the Microbleed Anatomical Rating Scale (MARS); 2) the burden and location of CMBs and their association with cognitive performances, independent of other clinical and neuroimaging features.nnnMETHODSnPatients underwent clinical, neuropsychological (4 cognitive domains), and MRI assessments. CMBs were assessed by three raters.nnnRESULTSnOut of the 152 patients (57.2% males; mean age±SD: 75.5±6.7years) with gradient-echo (GRE) sequences, 41 (27%) had at least one CMB. Inter-rater agreement for number and location of CMBs ranged from good to very good [multi-rater Fleiss kappa (95%CI): 0.70-0.95]. Lacunar infarcts and some clinical variables (e.g., hypertension and physical activity) were associated with CMBs in specific regions. Total number of CMBs and of those in deep and lobar regions were associated with attention/executive and fluency domains.nnnDISCUSSIONnMARS is a reliable instrument to assess CMBs in SVD patients with MCI. Nearly one third of these patients had at least one CMB. Total CMBs burden was associated with attention/executive functions and fluency domains impairment, lacunar infarcts, and with some potentially modifiable risk factors.

Lymphopenia, Infectious Complications, and Outcome in Spontaneous Intracerebral Hemorrhage

BackgroundLymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH).MethodsWe retrospectively analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. We identified subjects with lymphocyte count obtained within 24xa0h from onset, and AL was defined as lymphocyte count <1000/μL. Infectious complications were assessed through retrospective chart review. Association between AL, infections, and mortality was investigated using multivariable logistic regression.ResultsOf the 2014 patients meeting inclusion criteria, 548 (27.2%) had AL and 605 (30.0%) developed an infectious complication. Case-fatality at 90xa0days was 36.9%. Patients with AL had larger hematoma volumes, higher frequency of intraventricular hemorrhage, and lower Glasgow Coma Scale score on presentation (all pxa0<xa00.001). AL was independently associated with increased risk of pneumonia [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50–2.58, pxa0<xa00.001] and multiple infections (OR 1.84, 95% CI 1.24–2.71, pxa0=xa00.003). AL was also an independent predictor of 90-day mortality (OR 1.55, 95% CI 1.18–2.04, pxa0=xa00.002) after adjusting for confounders.ConclusionsAL is common in ICH patients and independently associated with increased risk of infectious complications and poor outcome. Further studies will be needed to determine whether prophylactic antibiotics in ICH patients with AL can improve outcome.

White matter microstructural damage and depressive symptoms in patients with mild cognitive impairment and cerebral small vessel disease: the VMCI-Tuscany Study.

Disruption of cortical‐subcortical circuits related to small vessel disease (SVD) may predispose to depression in the elderly. We aimed to determine the independent association between white matter (WM) microstructural damage, evaluated with diffusion tensor imaging (DTI), and depressive symptoms in a cohort of elderly subjects with mild cognitive impairment (MCI) and SVD.

Cerebrovascular Disease Knowledge Portal: An Open-Access Data Resource to Accelerate Genomic Discoveries in Stroke

Stroke is a leading cause of death and disability across the globe, affecting 15 million people each year.1 Stroke represents an archetypical common complex disease with both genetic and environmental determinants2,3 playing a role in its occurrence. The proportion of stroke risk that can be attributed to genetic variation has been estimated to be 30%.4–6 Although this estimate provides an indication of the overall importance of genetic variation in stroke, the key to developing new treatment strategies is to identify the specific genetic variants (mutations) that modify an individual’s risk of stroke. Genetic association studies (GWAS) seek to identify these variants and link them to specific genes, which, in turn, point to specific cellular processes to become therapeutic targets for drug development. In addition, newly discovered genetic risk loci can be used to improve existing phenotyping systems, enhance prediction tools aimed to identify high-risk patients, and aid in establishing causality for associations involving nongenetic exposures.nnSuccessfully identifying the range of genetic variants that cause stroke and leveraging these discoveries to reduce the suffering caused by this condition requires overcoming several key challenges. First, stroke is the final result of multiple different pathological processes and must, therefore, be accurately subtyped to identify underlying biology. Second, because large number of cases and controls are required to identify the culprit genetic variants, tens (even hundreds) of thousands of cases must be studied, requiring the collaboration of multiple centers, many of which use different ascertainment methods and criteria. Third, because genetic variation differs across the globe, representative populations from all ethnicities must be studied. Finally, all these data must be shared rapidly and widely to ensure the most expedited progress in research and enable investigators with the brightest ideas to utilize these data provided by patients to …

Cerebellar Hematoma Location: Implications for the Underlying Microangiopathy

Background and Purpose— Spontaneous cerebellar intracerebral hemorrhage (ICH) has been reported to be mainly associated with vascular changes secondary to hypertension. However, a subgroup of cerebellar ICH seems related to vascular amyloid deposition (cerebral amyloid angiopathy). We sought to determine whether location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small-vessel disease pathology (cerebral amyloid angiopathy or hypertensive vasculopathy). Methods— Consecutive patients with cerebellar ICH from a single tertiary care medical center were recruited. Based on data from pathological reports, patients were divided according to the location of the primary cerebellar hematoma (deep versus superficial). Location of cerebral microbleeds (CMBs; strictly lobar, strictly deep, and mixed CMB) was evaluated on magnetic resonance imaging. Results— One-hundred and eight patients (84%) had a deep cerebellar hematoma, and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in patients with superficial cerebellar ICH (89% versus 65%, respectively; P<0.05). Among patients who underwent magnetic resonance imaging, those with superficial cerebellar ICH had higher prevalence of strictly lobar CMB (43%) and lower prevalence of strictly deep or mixed CMB (0%) compared with those with deep superficial cerebellar ICH (6%, 17%, and 38%, respectively). In a multivariable model, presence of strictly lobar CMB was associated with superficial cerebellar ICH (odds ratio, 3.8; 95% confidence interval, 1.5–8.5; P=0.004). Conclusions— Our study showed that superficial cerebellar ICH is related to the presence of strictly lobar CMB—a pathologically proven marker of cerebral amyloid angiopathy. Cerebellar hematoma location may thus help to identify those patients likely to have cerebral amyloid angiopathy pathology.

Listeria monocytogenes brainstem infection (rhombencephalitis) mimicking ischemic stroke

The frequency of Listeria monocytogenes (Lm) infection of the central nervous system is increasing. We report a patient recently treated with chemotherapeutic drugs for pulmonary adenocarcinoma who suddenly developed hemiparesis, was initially diagnosed with stroke, and was then found to be affected by Lm rhombencephalitis accompanied by a brain abscess. Lm meningoencephalitis mimicking ischemic stroke is rare but must be considered, especially in specific patients.