Laura Ciolli

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.

Is type 2 diabetes related to leukoaraiosis? an updated review

A significantly increased interest has been dedicated to the study of the effects of diabetes mellitus (DM) on the brain. DM is associated with an increased risk of stroke and cognitive decline. In patients with DM, neuroimaging discloses with high‐frequency structural changes, such as cerebral atrophy, infarcts and white matter lesions, also called leukoaraiosis (LA), an expression of small vessel disease. A previous review showed a relation between DM and both cerebral atrophy and lacunar infarcts, while the question about the relation between DM and LA remained unanswered. In this review, we provide an update on data on this last association. In the reviewed studies, we examined the presence of DM, other disease characteristics, such as duration and complications, and laboratory markers of the disease such as blood glycated hemoglobin (HbA1c), insulin resistance, insulin concentrations and their association with LA. About 40% of the reviewed studies reported a statistically significant association between DM and LA. Long‐standing DM and a poor glycemic control were associated with severe LA. Studies using innovative MRI techniques, such as diffusion tensor imaging (DTI), reported a significant association between microstructural white matter alterations and DM. This review highlights more firmly than previously reported the existence of a relation between DM and both presence and severity of LA. These results are possibly due to more sensitive and advanced imaging techniques recently used to study the extent of LA. However, because of the heterogeneous methodology used in the reviewed studies, a definitive conclusion cannot be drawn.

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

Dementia is one of the most disabling conditions. Alzheimers disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD.

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.

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

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.

Clinical, familial, and neuroimaging features of CADASIL-like patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3‐negative patients with a phenotype closely resembling that of CADASIL.

Familial cerebral cavernous malformation: report of a further Italian family

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and may occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. This is a report on an Italian family affected by CCM due to a KRIT1 gene mutation on exon 13. The mother suffered from a cerebellar hematoma and was severely disabled; one son had suffered from intractable seizures and underwent surgery for removal of a cavernous angioma, while another son was asymptomatic. Brain MRI showed CCMs in all patients. This report underlines that a familial form of CCM could be suspected when a patient presents with multiple CCMs; neurologists and neurosurgeons should be aware that genetic testing for these forms is available.

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

BACKGROUND AND OBJECTIVES Cerebral 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. METHODS Patients underwent clinical, neuropsychological (4 cognitive domains), and MRI assessments. CMBs were assessed by three raters. RESULTS Out 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. DISCUSSION MARS 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.

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.

The Florence VAS-COG clinic: a model for the care of patients with cognitive and behavioral disturbances consequent to cerebrovascular diseases.

BACKGROUND AND OBJECTIVE Services dedicated to patients with cognitive and behavioral consequences of cerebrovascular diseases are not well established. In this paper, we report on the general organization of such a service (the Florence VAS-COG Clinic) after 9 years of activity, updating a previous work related to the first 5 years. METHODS The Florence VAS-COG clinic, started in 2006, is an outpatient service dedicated to the assessment and follow-up of patients with cerebrovascular diseases and related cognitive, psychiatric, and behavioral disturbances. The staff involved in the clinic is composed of certified neurologists, one neuropsychologist, and neurology residents. The diagnostic protocol includes detailed personal and family history, general and neurologic examinations, and functional, neuropsychological, and neuroimaging assessment. After this work-up, comprehensive diagnoses are made. RESULTS From January 2006 to March 2014, 600 patients (mean age 67.3 years ± 13.9; 52% females) have been evaluated in the clinic. Cognitive impairment, including mild cognitive impairment and dementia, mainly of vascular origin, was the most common (36.4%) diagnostic category, followed by suspected or confirmed familial micro-angiopathy (35.8%). Compared to the first years of activity, we are now facing the need of augmenting the number of visits due to increasing request and to better implement the multidisciplinarity of the team. Efforts are currently directed towards the definition of management protocols in pharmacological and non-pharmacological strategies. CONCLUSIONS The establishment of a VAS-COG clinic represents an important step for the appreciation of the patient clinical needs and for the implementation of screening, diagnostic, and treatment options in the field of the neuropsychiatric consequences of cerebrovascular diseases.