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

Abstract

Dementia is one of the most disabling conditions. Alzheimer's 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

“…The vascular MCI (VMCI)-Tuscany study is an ongoing multicenter, prospective, observational study aimed at evaluating predictors of the transition from VMCI (defined by the presence of moderate-to-severe white matter lesions) to dementia [12]. The study methodology has been reported elsewhere [12].…”

“…The study methodology has been reported elsewhere [12]. To be included, outpatients, referred from neurologic or geriatric units, had to be classified as affected by MCI with SVD according to the following inclusion criteria: (1) MCI defined according to Winblad et al's criteria [3] and (2) evidence on magnetic resonance imaging (MRI) of moderate-to-severe degrees of white matter hyperintensities (WMH) according to the modified version of the Fazekas scale [13].…”

“…The modified Fazekas scale is a visual scale based on a categorization into three severity classes: grade 1 (mild WMH) 5 single lesions ,10 mm, areas of "grouped" lesions ,20 mm in any diameter; grade 2 (moderate WMH) 5 single lesions between 10 and 20 mm, areas of "grouped" lesions .20 mm in any diameter, no more than "connecting bridges" between individual lesions; and grade 3 (severe WMH) 5 single lesions or confluent areas of hyperintensity 20 mm in any diameter. According to the study protocol, each patient underwent an extensive clinical and neuropsychological assessment and an MRI examination [12]. The study was approved by local ethics committees, and each patient gave a written informed consent.…”

The Gothenburg MCI study: Design and distribution of Alzheimer’s disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up

“…A similar approach characterizes the Vascular Mild Cognitive Impairment Tuscany Study. 66 In clinical-pathologic studies, the prevalence rate of MixD is highly variable between 2% and 60% 8 indicating lack of clarifying knowledge about the relationship between vascular lesions, neurodegeneration, and the clinical manifestations. Almost 1/3 of the included patients exhibited mild dementia at baseline, where 42% had AD, 21% MixD, and 14% SVD.…”

The rehabilitation of attention in patients with mild cognitive impairment and brain subcortical vascular changes using the Attention Process Training-II. The RehAtt Study: rationale, design and methodology

“…The VMCI-Tuscany study is a multicenter, prospective, observational study aimed at evaluating predictors of the transition from MCI with SVD to dementia [23]. The outpatient VAS-COG clinic is entirely dedicated to assess and follow-up patients affected by cognitive, psychiatric, and behavioral disturbances caused or associated with cerebrovascular diseases, and it is active since January 2006 [24].…”