Cognitive improvement following endovascular embolization in patients with intracranial dural arteriovenous fistula: The Neuropsychology in dural ArterIal Fistula (NAIF) Study.

BACKGROUND: Cognitive improvement after endovascular embolization of an intracranial dural arteriovenous fistula (dAVF) remains unexplored. We aim to investigate cognitive changes following endovascular embolization of dAVFs. METHODS: Neuropsychology in dural ArterIal Fistula (NAIF) was a prospective multicentric study including patients with an angiographic diagnosis of dAVF who underwent endovascular embolization over the course of 4 years. A complete neuropsychological evaluation comprising five cognitive domains (attention and executive functions, memory, language, praxis, gnosis) was performed at baseline and 3 months follow-up. Mean Z scores for cognitive tests were compared pre- and post-treatment using paired sample t-tests, where higher Z scores indicate better cognition. Effect sizes were computed as Cohen's d. RESULTS: A total of 32 patients (mean age 61.1±15.4 years, 10 (31.3%) females) were included. Patients exhibited improved performance in attention and executive functions: executive functions-attention (+0.282, P=0.009, d=0.29), executive functions-fluencies (+0.283, P=0.029, d=0.4), and executive functions-processing speed (+0.471, P=0.039, d=0.41). There was an increase in memory: verbal learning and verbal delayed recall scores (+0.513, P<0.001, d=0.55, and +0.385, P=0.001, d=0.41, respectively), while verbal recognition parameters (+0.839, P=0.086, d=0.37) and visual memory (delayed recall) (+0.430, P=0.060, d=0.35) displayed trends toward improved performance. Regarding language, there was significant overall improvement (+0.300, P=0.014, d=0.24), but neither praxis nor gnosis changed significantly. These cognitive outcomes were independent of the severity (measured as Cognard classification), and no patient experienced cognitive worsening. CONCLUSION: This study suggests that endovascular embolization confers cognitive benefits on dAVF patients undergoing endovascular embolization and may be beneficial even for patients with a low risk of hemorrhage.

Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort.

Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aß1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI). Materials and methods: Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, chronic obstructive pulmonary disease and smoking habit, using the Normal AT(N) group as the reference category. Results: The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, p > 0.16). The interaction between sex and AT(N) groups had no effect on differentiating VD. Lastly, CSF Aß1-42, p181-tau and t-tau measures were not correlated to VD (all r < 0.13; p > 0.13). Discussion: Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort.

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.

Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

Neurological damage after transcatheter aortic valve implantation compared with surgical aortic valve replacement in intermediate risk patients.

BACKGROUND AND PURPOSE: The risk of neurological damage following transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) in severe aortic stenosis patients deemed to be at intermediate surgical risk is unknown. In this target population, the degree of neurological damage was compared using brain diffusion-weighted magnetic resonance imaging (DW-MRI) and cognitive testing. METHODS: Forty-six consecutive patients undergoing TAVI (78.0 ± 8.3 years; STS score 4.4 ± 1.7) and 37 patients undergoing SAVR (78.9 ± 6.2 years, STS score 4.7 ± 1.7) were compared. DW-MRI was performed in 67 patients (40 in TAVI vs. 27 in SAVR group) within the first 15 days post-procedure. A cognitive assessment was performed at baseline and at 3 months follow-up. The occurrence of potential cognitive impairment post-intervention was determined using the reliable change index (RCI). RESULTS: Baseline characteristics were comparable in TAVI and SAVR groups except for the presence of severe calcified aorta, which occurred more frequently in the TAVI group [17 (37 %) vs. 0 (0 %), p < 0.001]. Three patients presented a clinical stroke: 1 (2.2 %) in TAVI group vs. 2 (5.4 %) in SAVR group, (p = 0.58). No differences were observed in the rate of acute ischemic cerebral lesions detected by DWI in patients undergoing TAVI vs. SAVR [18 (45 %) in TAVI vs. 11 (40.7 %) in SAVR, adjusted OR 0.95; 95 % CI 0.25-3.65; p = 0.94]. TAVI was associated with a lower number of DWI lesions (adjusted OR 0.54; 95 % IC 0.37-0.79; p = 0.02). An older age was a predictor of the occurrence of acute lesions (OR 1.13; 95 % CI 1.03-1.23; p = 0.01), and the use of vitamin-K antagonist therapy had a protective effect (OR 0.25; 95 % CI 0.07-0.92; p = 0.037) regardless the type of intervention. Overall no significant changes were observed in global cognitive scores post-intervention (p = 0.23). The RCI showed mild cognitive decline in nine patients undergoing TAVI (26.4 %) and in six patients in the SAVR group (30.0 %) (p = 0.96). There was no association between the number and total volume of lesions and the occurrence of cognitive decline (CC Spearman 0.031, p = 0.85 and -0.011, p = 0.97, respectively). CONCLUSIONS: TAVI and SAVR were associated with a similar rate of acute silent ischemic cerebral lesions in intermediate risk patients. Although acute lesions occurred very frequently in both strategies, their cognitive impact was not clinically relevant.

Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer's Disease.

The objective of this study was to identify genetic variation in genes encoding death receptors and signals that modulate their activity. After conducting a meta-analysis with five previous genome-wide association studies and aggregated data, the most significant signals, (TNF locus: rs2395488, rs2534672, and rs9267445; and FASLG locus: rs730278), were replicated in 1,046 cases and 372 controls. The rs2395488 and rs2534672 markers showed a modest protective effect (OR = 0.849, p = 0.49780;OR= 0.687, p = 0.11335), in contrast to rs730278 marker (OR = 1.146, p = 0.17212), which did not follow the previous effect direction; in any case it reached the significance level. Final meta-analysis, adding the replication sample, confirmed these observations. We concluded that FASLG marker is not etiologically linked to Alzheimer's disease. However, single nucleotide polymorphisms around TNF locus require further analyses in order to explain the association between Alzheimer's disease and human leukocyte antigen.