Hippocampal atrophy and white matter lesions characteristics can predict evolution to dementia in patients with vascular mild cognitive impairment.

BACKGROUND: Vascular mild cognitive impairment (VMCI) is a transitional condition that may evolve into Vascular Dementia(VaD). Hippocampal volume (HV) is suggested as an early marker for VaD, the role of white matter lesions (WMLs) in neurodegeneration remains debated. OBJECTIVES: Evaluate HV and WMLs as predictive markers of VaD in VMCI patients by assessing: (i)baseline differences in HV and WMLs between converters to VaD and non-converters, (ii) predictive power of HV and WMLs for VaD, (iii) associations between HV, WMLs, and cognitive decline, (iv)the role of WMLs on HV. METHODS: This longitudinal multicenter study included 110 VMCI subjects (mean age:74.33 ± 6.63 years, 60males/50females) from the VMCI-Tuscany Study database. Subjects underwent brain MRI and cognitive testing, with 2-year follow-up data on VaD progression. HV and WMLs were semi-automatically segmented and measured. ANCOVA assessed group differences, while linear and logistic regression models evaluated predictive power. RESULTS: After 2 years, 32/110 VMCI patients progressed to VaD. Converting patients had lower HV(p = 0.015) and higher lesion volumes in the posterior thalamic radiation (p = 0.046), splenium of the corpus callosum (p = 0.016), cingulate gyrus (p = 0.041), and cingulum hippocampus(p = 0.038). HV alone did not fully explain progression (p = 0.059), but combined with WMLs volume, the model was significant (p = 0.035). The best prediction model (p = 0.001) included total HV (p = 0.004) and total WMLs volume of the posterior thalamic radiation (p = 0.005) and cingulate gyrus (p = 0.005), achieving 80% precision, 81% specificity, and 74% sensitivity. Lower HV were linked to poorer performance on the Rey Auditory-Verbal Learning Test delayed recall (RAVLT) and Mini Mental State Examination (MMSE). CONCLUSIONS: HV and WMLs are significant predictors of progression from VMCI to VaD. Lower HV correlate with worse cognitive performance on RAVLT and MMSE tests.

Expanding the Neurological Phenotype of Anderson-Fabry Disease: Proof of Concept for an Extrapyramidal Neurodegenerative Pattern and Comparison with Monogenic Vascular Parkinsonism.

Anderson-Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations.

Prestroke Cognitive Impairment: Frequency and Association With Premorbid Neuropsychiatric, Functional, and Neuroimaging Features.

BACKGROUND: Some patients with stroke have prestroke cognitive impairment (pre-SCI), but its etiology is not clear. The aim of this cross-sectional study was to assess the frequency of pre-SCI and its association with premorbid neuropsychiatric, functional, and neuroimaging features. METHODS: Patients hospitalized in stroke unit with an informant who could complete IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) were included. Pre-SCI was diagnosed if the IQCODE score was >3.3. Prestroke assessment also included NPI-Q (Neuropsychiatric Inventory Questionnaire), the basic Activities of Daily Living and Instrumental Activities of Daily Living scales, and the Clinical Dementia Rating scale. A multivariate logistic regression model was used to evaluate the association of pre-SCI with age, sex, education, arterial hypertension, atrial fibrillation, white matter lesions, cerebral microbleeds, and pathological medial temporal lobe atrophy. RESULTS: IQCODE was available in 474 of 520 patients (91.2%; 45% women; mean age 75.5±13.3 years). Pre-SCI had a prevalence of 32.5% and was associated with prestroke NPI-Q (pre-SCI absent versus present, 1.7±2.3 versus 5.5±4.9; P<0.001), Activities of Daily Living scale (0.3±0.8 versus 1.8±1.9; P<0.001), Instrumental Activities of Daily Living scale (0.6±1.3 versus 3.8±4.0; P<0.001), and Clinical Dementia Rating scale score (0.7±1.7 versus 7.2±6.2; P<0.001). In the 271 patients with a magnetic resonance imaging available, the multivariate logistic regression showed that age (odds ratio [OR], 1.05 [95% CI, 1.62-9.73]), white matter lesions (OR, 1.26 [95% CI, 1.003-1.58]), and a pathological medial temporal lobe atrophy score (OR, 3.97 [95% CI, 1.62-9.73]) were independently associated with pre-SCI. In the 218 patients with ischemic stroke, white matter lesions (OR, 1.34 [95% CI, 1.04-1.72]) and medial temporal lobe atrophy (OR, 3.56 [95% CI, 1.38-9.19]), but not age, were associated with pre-SCI. CONCLUSIONS: One-third of patients admitted to a stroke unit have pre-SCI that is associated with preexisting neuropsychiatric symptoms and functional performance. White matter lesions and medial temporal lobe atrophy are associated with pre-SCI, suggesting that both small vessel disease and neurodegeneration might be involved in its etiology.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

Brain health assessment. An exploratory review of tools related to its cognitive dimension.

Background: Brain health is an evolving concept and relates to physical and mental health, social well-being, productivity, creativity. Brain health has several dimensions (cognitive, motor, functional, social, and emotional), and should be recognized as one top global priorities of health policies. The purpose of this paper is to provide a summary of tools developed for assessing the cognitive dimension of brain health in the out-patient services. Methods: A literature search on PubMed was performed (from inception to May 31, 2023). We identified cognitive tests, functional and psychological scales, and focused on screening tools specifically proposed to characterize cognition within the construct of brain health, comparing them with common global screening tests. Results: Among 1947 records, we identified 17 cognitive screening tools used in the context of brain health assessment, of which four were ad hoc developed: Brain Health Assessment (BHA), Brain Health Test (BHT), Brain Health Test-7 (BHT-7), and The Cogniciti Brain Health Assessment. The four tests have administration time ranging from 4 to 30 min, and different administration methods (paper-and-pencil or tablet-based). All four tools assess memory and other cognitive domains. Specific cut-offs have been identified for BHT and BHT-7, while the other tools have automated scoring systems. All but one test also assess other dimensions. Compared to commonly used cognitive screening tests, the brain health tools are less widely used, translated, and validated. Conclusions: The concept of brain health is new and requires further validation of tools for its assessment, especially for the cognition dimension.