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Background/Aims: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) is a widely used rating instrument. The Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) includes additional tests reflecting mental speed and executive functions. The objective of this study was to compare the results of the two scales among subjects with various degrees of white matter hyperintensities (WMHs). Methods:In the multicentre, multinational Leukoaraiosis and Disability in the Elderly (LADIS) study, 616 non-disabled subjects between the ages of 65 and 84 were examined using MRI, the ADAS-cog and VADAS-cog. The WMH rating from the MRI divided the patients into groups of mild (n = 280), moderate (n = 187) and severe (n = 149) degrees of change. Results: Covariance analysis controlling for the effect of age and education revealed that the ADAS-cog differentiated only the mild and severe WMH groups, while the differences between all three groups were highly significant with the VADAS-cog. Conclusions:The VADAS-cog significantly differentiated between all the white matter groups. In comparison, the ADAS-cog differentiated only severe changes. Accordingly, the VADAS-cog may be a more sensitive endpoint in studies of patients with white matter load and vascular burden of the brain. Copyright (c) 2007 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions.Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH).Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors.Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing--namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion.Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed. [ABSTRACT FROM AUTHOR]

We report the genome sequence of Lentilitoribacter sp. strain EG35 isolated from the octocoral Eunicella gazella sampled off the coast of Portugal. We reveal the coding potential for the biosynthesis of polyhydroxyalkanoates - biodegradable polyesters that may serve bioplastics production, diverse homoserine lactone-like communication signals, and four putatively novel natural products.

Common variable immunodeficiency (CVID) is a primary disorder characterized by impaired B cell differentiation and defective immunoglobulin production. This condition often presents with a wide range of clinical manifestations, including increased frequency and severity of infections, autoimmune diseases, and inflammatory disorders, which can lead to delays in diagnosis. Granulomatous involvement of the brain is an extremely rare but severe manifestation of CVID. We present a case of a woman in her 30s with a history of Evans syndrome and lymphocytic alveolitis who was admitted with persistent headache without neurological symptoms. Imaging revealed multiple infiltrative brain lesions. Despite the absence of recurrent infections, the patient's history of autoimmune manifestations and immunoglobulin deficiencies led to the diagnosis of CVID without the need for a brain biopsy. Treatment with intravenous immunoglobulin and immunosuppressive therapy resulted in significant clinical improvement and resolution of brain lesions. This case highlights the importance of considering CVID in patients with autoimmune manifestations and the effectiveness of prompt immunoglobulin replacement and immunosuppression in managing severe presentations of this condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rocha et al.)

Background: Patients with heart failure (HF) often have multiple cardiovascular risk factors (CVRF) and comorbidities (CMB). We evaluated the impact of additive CMB and CVRF in HF prognosis., Methods: We retrospectively analyzed ambulatory patients with systolic dysfunction between January 2012 and May 2018. Follow-up: until January 2021. Endpoint: all-cause death. CVRF analyzed: Arterial hypertension, Diabetes mellitus and smoking. CMB evaluated: coronary artery disease, non-coronary atherosclerotic disease, respiratory disease, dementia, anemia, chronic kidney disease, inflammatory/autoimmune disease, active cancer and atrial fibrillation. Classification according to the number of CVRF and/or CMB: < 2 and ≥ 2. The independent prognostic impact of CVRF/CMB burden was assessed with multivariate Cox-regression., Results: Most patients had ≥ 2 CMB (67.9%). Regarding CVRF, 14.9% presented none, 40.2% had one and 32.1% had two. During a median 49-month follow-up, 419 (49.1%) patients died. Mortality was higher among patients with ≥2 CVRF (56.1 vs 43.4% in those with <2) and in those with ≥2 CMB (57.7 vs 31.0%). While patients with one CMB had similar mortality than those with none. Patients with ≥2 CMB had higher long-term mortality risk: HR=2.47 (95% CI: 1.95-3.14). In patients with ≥2CVRF: HR of dying = 1.39 (1.14- 1.70). When taken together there was a clear survival disadvantage for patients with ≥ 2 CVRF/CMB - adjusted HR: 2.20 (1.45-3.34)., Conclusion: The presence of only 2 CVRF/CMB more than doubles the patients´ risk of dying. CVRF and CMB should be assessed as part of routine patient management., Competing Interests: Conflicts of interest and Source of Funding: None., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or non-thrombotic manifestations in patients with persistent antiphospholipid antibodies (aPL). Catastrophic APS is a rare and severe form of APS that is defined by the presence of multiple vascular occlusive events. When a patent foramen ovale (PFO) is present, paradoxical embolization can occur, simultaneously leading to arterial and venous thrombosis. We present a complex clinical case of a patient who presented with multiple arterial and venous thrombotic events with positive aPL. The suspicion of catastrophic APS was removed when a PFO was found in a transesophageal echocardiogram, justifying paradoxical embolization. This emphasizes the importance of searching for PFO in patients with APS presenting with simultaneous venous and arterial thrombosis for management and prognosis purposes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rocha et al.)

Background: Vascular cognitive impairment is frequent, in mild (mVCI) or severe forms (vascular dementia)., Objective: To do a randomized controlled-trial to evaluate the impact of physical activity on cognition (primary outcome), neurocognitive measures, quality of life, functional status, and physical function (secondary outcomes), in patients with mVCI., Methods: A hundred and four patients with mVCI (mean age 71.2 years; 53 women) were randomized for a six-month intervention of moderate physical activity (60-minute sessions, 3 times/week) (n = 53) or best-practice "usual care" (n = 51). Comprehensive evaluations of primary and secondary outcomes included an objective measure of physical activity through accelerometry at baseline and after intervention., Results: Mean session attendance was 58%. Adverse events were negligible. After 6 months, no significant primary outcome change was observed, either in the intervention or 'usual care' group. The intervention group improved significantly in some secondary outcomes in physical function - aerobic capacity (U = 403; p = 0.000) and agility (U = 453; p = 0.005) after 6 months. Regardless of randomization arm, a post-hoc analysis based on fulfilling at least 21.5 minutes/day of moderate or 10.7 minutes/day of vigorous physical activity (World Health Organization-WHO standards) revealed improvements. These were not only in motor capacity but also on the global measure of cognition, executive functions and memory., Conclusions: Physical activity was safe and beneficial regarding domains of physical function. No significant cognitive decline was registered over 6-months, regardless of intervention allocation. Larger samples, longer follow-ups and focus on intervention adherence are needed to fully analyze the impact of WHO recommendations for physical activity in mVCI populations.

Introduction: The prognostic implications of using benzodiazepines (BZD) in heart failure (HF) patients are still unknown., Objectives: This study aimed to assess the association of BZD use with all‑cause death in ambulatory, chronic HF patients., Patients and Methods: We investigated a retrospective cohort of ambulatory HF patients with left ventricular systolic dysfunction (LVSD). The patients were followed up from their first medical appointment until January 2021 and all‑cause mortality was the primary end point. The Cox regression analysis was used to assess the association between BZD use and all‑cause mortality. Subgroup analyses were performed considering age, sex, body mass index (BMI), respiratory disease, chronic kidney disease (CKD), and New York Heart Association (NYHA) class. Multivariable models were built to account for confounders., Results: We studied 854 patients (69% men), of mean (SD) age 71 (13) years, of whom 51% had severe LSVD, and 242 (28.3%) regularly used BZD. During a median follow‑up of 46 months, 443 patients (51.9%) died. BZD use predicted no crude survival disadvantage in the entire investigated group and in the subgroup analysis according to sex, respiratory disease, BMI, and NYHA class. BZD use was not mortality‑associated among patients aged 75 years and younger. However, in those older than 75 years the hazard ratio (HR) of all‑cause death was 1.3 (95% CI, 0.99-1.69; P = 0.06). BZD use seemed safe in the patients without CKD, but in those with CKD it was associated with worse survival (HR, 1.33; 95% CI, 1.02-1.73). In a multivariable‑adjusted analysis, the use of BZD was independently associated with increased death risk (HR, 1.36; 95% CI, 1.06-1.75)., Conclusions: The patients medicated with BZD presented a 36% higher risk of dying. BZD should probably be used with caution, particularly in older HF patients and in those with CKD.

Bone tissue engineering emerged as a solution to treat critical bone defects, aiding in tissue regeneration and implant integration. Mainly, this field is based on the development of scaffolds and coatings that stimulate cells to proliferate and differentiate in order to create a biologically active bone substitute. In terms of materials, several polymeric and ceramic scaffolds have been developed and their properties tailored with the objective to promote bone regeneration. These scaffolds usually provide physical support for cells to adhere, while giving chemical and physical stimuli for cell proliferation and differentiation. Among the different cells that compose the bone tissue, osteoblasts, osteoclasts, stem cells, and endothelial cells are the most relevant in bone remodeling and regeneration, being the most studied in terms of scaffold-cell interactions. Besides the intrinsic properties of bone substitutes, magnetic stimulation has been recently described as an aid in bone regeneration. External magnetic stimulation induced additional physical stimulation in cells, which in combination with different scaffolds, can lead to a faster regeneration. This can be achieved by external magnetic fields alone, or by their combination with magnetic materials such as nanoparticles, biocomposites, and coatings. Thus, this review is designed to summarize the studies on magnetic stimulation for bone regeneration. While providing information regarding the effects of magnetic fields on cells involved in bone tissue, this review discusses the advances made regarding the combination of magnetic fields with magnetic nanoparticles, magnetic scaffolds, and coatings and their subsequent influence on cells to reach optimal bone regeneration. In conclusion, several research works suggest that magnetic fields may play a role in regulating the growth of blood vessels, which are critical for tissue healing and regeneration. While more research is needed to fully understand the relationship between magnetism, bone cells, and angiogenesis, these findings promise to develop new therapies and treatments for various conditions, from bone fractures to osteoporosis.

Difficult-to-treat infections make complex wounds a problem of great clinical and socio-economic impact. Moreover, model therapies of wound care are increasing antibiotic resistance and becoming a critical problem, beyond healing. Therefore, phytochemicals are promising alternatives, with both antimicrobial and antioxidant activities to heal, strike infection, and the inherent microbial resistance. Hereupon, chitosan (CS)-based microparticles (as CM) were designed and developed as carriers of tannic acid (TA). These CMTA were designed to improve TA stability, bioavailability, and delivery in situ. The CMTA were prepared by spray dryer technique and were characterized regarding encapsulation efficiency, kinetic release, and morphology. Antimicrobial potential was evaluated against methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA), Staphylococcus epidermidis, Escherichia coli , Candida albicans , and Pseudomonas aeruginosa strains, as common wound pathogens, and the agar diffusion inhibition growth zones were tested for antimicrobial profile. Biocompatibility tests were performed using human dermal fibroblasts. CMTA had a satisfactory product yield of ca. 32% and high encapsulation efficiency of ca. 99%. Diameters were lower than 10 μm, and the particles showed a spherical morphology. The developed microsystems were also antimicrobial for representative Gram+, Gram-, and yeast as common wound contaminants. CMTA improved cell viability (ca. 73%) and proliferation (ca. 70%) compared to free TA in solution and even compared to the physical mixture of CS and TA in dermal fibroblasts.

Background: The World Health Organization (WHO) recommends a minimum of 150 minutes of moderate physical activity per week. Adherence to these recommendations is difficult to assess., Objective: We aimed to evaluate the validity of self-reported physical activity in mild vascular cognitive impairment (mVCI) and whether physical activity was associated with cognitive status, by using baseline data from a randomized controlled trial., Methods: A hundred and four subjects with mVCI were included (mean age 72 years; 51% women). Subjects underwent neurological, physical, and comprehensive neuropsychological assessments. Adherence to WHO physical activity recommendations was evaluated using both self-reported information and objective measures (accelerometry)., Results: There was poor agreement (kappa = 0.106) between self-report of following WHO recommendations and actually fulfilling them according to accelerometry. Only 16.6% of participants reported following WHO recommendations and displayed compatible values according to the accelerometer. Participants whose accelerometry values confirmed adherence to WHO recommendations had better performance in a global measure of cognition, attention, and mental speed processing. In multiple regression analyses, education and accelerometry values in accordance with WHO recommendations were independently associated with the global measure of cognition, attention, and processing speed, controlling for sex, age, and depressive symptoms. Accelerometry results were not associated with memory and executive functions., Conclusion: In this sample of mVCI subjects, self-reported physical activity displayed poor agreement with accelerometry values, suggesting that objective measures of physical activity are preferable. Physical activity (performed, at least, according to WHO recommendations) was associated with better cognitive performance overall.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi ( P <0.001 for global cognitive function, processing speed, executive functions, and memory and P <0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes ( P <0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

Background: Cognitive impairment and cerebrovascular pathology are both frequent with ageing. Cognitive impairment due to vascular pathology of the brain, termed vascular cognitive impairment (VCI), is one of the most frequent causes of cognitive impairment in elderly subjects. Thus far, VCI has no specific pharmacological treatment. Recent observational studies have suggested a protective effect of physical activity in cognition, but adequate randomised controlled trials (RCT) are lacking., Methods: AFIVASC is a multi-centre randomised controlled trial, with a 6-month intervention treatment and an additional follow-up of 6 months, that aims to estimate the impact of 6 months of moderate intensity physical activity on cognition (the primary outcome) at 6 and 12 months in subjects with VCI. Participants are community dwellers with criteria for VCI without dementia or who have had previous stroke or transient ischaemic attack (TIA). Patients may be self-referred or referred from a medical appointment. After confirming the inclusion criteria, a run-in period of 1 month is conducted to access adherence; only after that are subjects randomly assigned (using a computerised program blinded to clinical details) to two groups (intervention group and best practice usual care group). The intervention consists of three physical activity sessions of 60 min each (two supervised and one unsupervised) per week. The primary outcome is measured by the presence or absence of decline in cognitive status. Secondary outcomes include changes in neuro-cognitive measures, quality of life, and functional and motor status. Primary and secondary outcomes are evaluated at 6 and 12 months by investigators blinded to both intervention and randomisation. A required sample size of 280 subjects was estimated. Statistical analyses will include regression analysis with repeated measures. The study was approved by the Ethics Committee for Health of Centro Hospitalar de Lisboa Norte (ref. no. 1063/13) and by the Ethics Committee for Health of Centro Hospitalar do Porto CHP (ref. no. 2016.055(049-DEFI/048-CES))., Discussion: We aim to show whether or not moderate physical activity has a beneficial impact on cognition, quality of life, motor, and functional status in people with vascular cognitive impairment, and to generate new insights on the applicability of implementing physical activity in this specific population., Trial Registration: ClinicalTrials.gov, NCT03578614 July 6, 2018.

Background: Cerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical symptoms has been modest, however, and thus the outcome may be affected by various host factors. We investigated the predictive value of educational and occupational attainments as proxy measures of cognitive reserve on long-term cognitive and functional outcome in patients with different degrees of WMH., Methods: In the Leukoaraiosis and Disability (LADIS) study, 615 older individuals with WMH were evaluated with brain MRI and detailed clinical and neuropsychological assessments at 3-year follow-up. A prolonged follow-up of functional and cognitive status was administered with a structured telephone interview after up to 7 years., Results: Higher levels of educational and occupational attainment were strongly related to baseline cognitive scores and predicted a slower rate of decline at 3-year follow-up in measures of processing speed, executive functions and memory independently of WMH volume and other confounders. The deleterious effect of WMH on processing speed and memory was moderated by education and occupation. Education mitigated the relation of WMH volume on 7-year cognitive status. Moreover, higher education and occupational attainments were related to favourable outcome at 7-year follow-up as defined by sustained functional independence and lower mortality., Conclusions: The results support the presumption that cognitive reserve plays a significant role as a buffer against the clinical manifestations of SVD and may in part explain high individual variability in outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up., Methods: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed., Results: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (β = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up., Conclusion: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years., (© 2016 S. Karger AG, Basel.)

White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a "pre-visible" stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment.

Objectives: Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes (ARWMC)., Methods: Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective cohort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used., Results: Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (± 5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (± 1.7)) who had not progressed to MCI or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: β: 0.39, 95% CI: 0.13-0.90, p = 0.008; follow-up: β: 0.24, 95% CI: 0.10-0.38, p = 0.001) and processing speed (baseline: β: 0.48, 95% CI: 0.14-0.89, p = 0.005; follow-up: β: 0.15, 95% CI: 0.02-0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3-year follow-up scores, executive function remained significant (β: 0.11, 95% CI: 0-0.22, p = 0.04)., Conclusion: Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC., (Copyright © 2014 John Wiley & Sons, Ltd.)

Purpose: To analyze speech expressiveness in a group of executives based on perceptive and acoustic aspects of vocal dynamics., Methods: Four male subjects participated in the research study (S1, S2, S3, and S4). The assessments included the Kingdomality test to obtain the keywords of communicative attitudes; perceptive-auditory assessment to characterize vocal quality and dynamics, performed by three judges who are speech language pathologists; perceptiveauditory assessment to judge the chosen keywords; speech acoustics to assess prosodic elements (Praat software); and a statistical analysis., Results: According to the perceptive-auditory analysis of vocal dynamics, S1, S2, S3, and S4 did not show vocal alterations and all of them were considered with lowered habitual pitch. S1: pointed out as insecure, nonobjective, nonempathetic, and unconvincing with inappropriate use of pauses that are mainly formed by hesitations; inadequate separation of prosodic groups with breaking of syntagmatic constituents. S2: regular use of pauses for respiratory reload, organization of sentences, and emphasis, which is considered secure, little objective, empathetic, and convincing. S3: pointed out as secure, objective, empathetic, and convincing with regular use of pauses for respiratory reload and organization of sentences and hesitations. S4: the most secure, objective, empathetic, and convincing, with proper use of pauses for respiratory reload, planning, and emphasis; prosodic groups agreed with the statement, without separating the syntagmatic constituents., Conclusion: The speech characteristics and communicative attitudes were highlighted in two subjects in a different manner, in such a way that the slow rate of speech and breaks of the prosodic groups transmitted insecurity, little objectivity, and nonpersuasion.

Objective: Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC)., Methods: The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3., Results: 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline., Conclusions: DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction.

Objective: A study was undertaken to determine whether diffusion-weighted imaging (DWI) abnormalities in normal-appearing brain tissue (NABT) and in white matter hyperintensities (WMH) predict longitudinal cognitive decline and disability in older individuals independently of the concomitant magnetic resonance imaging (MRI) findings., Methods: A total of 340 LADIS (Leukoaraiosis and Disability Study) participants, aged 65 to 84 years, underwent brain MRI including DWI at baseline. Neuropsychological and functional assessments were carried out at study entry and repeated annually over a 3-year observational period. Linear mixed models and Cox regression survival analysis adjusted for demographics, WMH volume, lacunes, and brain atrophy were used to evaluate the independent effect of the DWI measures on change in cognitive performance and functional abilities., Results: The mean global apparent diffusion coefficient (ADC) and the relative peak height and peak position of the ADC histogram in NABT predicted faster rate of decline in a composite score for speed and motor control. Higher mean ADC and lower peak height were also related to deterioration in executive functions and memory (specifically working memory), with peak height also being related to more rapid transition to disability and higher rate of mortality. Mean ADC in WMH had less pronounced effects on cognitive and functional outcomes., Interpretation: DWI microstructural changes in NABT predict faster decline in psychomotor speed, executive functions, and working memory regardless of conventional MRI findings. Moreover, these changes are related to functional disability and higher mortality., (Copyright © 2013 American Neurological Association.)

Age-related white matter changes have been associated with cognitive functioning, even though their role is not fully understood. This work aimed to test a 3-factor model of the neuropsychological assessment battery and evaluate how the model fit the data longitudinally. Confirmatory factor analysis (CFA) was used to investigate the dimensions of a structured set of neuropsychological tests administered to a multicenter, international sample of independent older adults (LADIS study). Six hundred and thirty-eight older adults completed baseline neuropsychological, clinical, functional and motor assessments, which were repeated each year for a 3-year follow-up. CFA provided support for a 3-factor model. These factors involve the dimensions of executive functions, memory functions, and speed and motor control abilities. Performance decreased in most neuropsychological measures. Results showed that executive functioning, memory and speed of motor abilities are valid latent variables of neuropsychological performance among older adults, and that this structure is relatively consistent longitudinally, even though performance decreases with time.

Cross-sectional studies have suggested that corpus callosum (CC) atrophy is related to impairment in global cognitive function, mental speed, and executive functions in the elderly. Longitudinal studies confirming these findings have been lacking. We investigated whether CC tissue loss is associated with change in cognitive performance over time in subjects with age-related white matter lesions (WML). Two-hundred-fifty-three subjects, aged 65-84 years, were evaluated by using repeated MRI and neuropsychological evaluation at baseline and after 3 years. The effect of overall and regional CC tissue loss on cognitive decline was analyzed with hierarchical linear regression models. After controlling for age, sex, education, and baseline cognitive performance, the rates of tissue loss in the total CC area, and in rostrum/genu and midbody subregions were significantly associated with decline in a compound measure of cognitive speed and motor control, but not in those of executive functions, memory, or global cognitive function. Total CC area and midbody remained significant predictors of speed also after adjusting for baseline WML volume, WML progression, and global brain atrophy. However, the relationship between anterior CC and speed performance was mediated by WML volume. In conclusion, the overall and regional rate of CC tissue loss parallels longitudinal slowing of psychomotor performance. The adverse effect of CC tissue loss on psychomotor function may be driven by altered interhemispheric information transfer between homologous cortical areas., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Spectrographic analysis of male actors' voices showed a cluster, the "actor's formant" (AF), which is related to the perception of good and projected voice quality. To date, similar phenomena have not been described in the voices of actresses. Therefore, the objective of the current investigation was to compare actresses' and nonactresses' voices through acoustic analysis to verify the existence of the "AF" cluster or the strategies used to produce the performing voice. Thirty actresses and 30 nonactresses volunteered as subjects in the present study. All subjects read a 40-second text at both habitual and loud levels. Praat (v.5.1) was then used to analyze equivalent sound pressure level (Leq), speaking fundamental frequency (SFF), and in the long-term average spectrum window, the difference between the amplitude level of the fundamental frequency and first formant (L1-L0), the spectral tilt (alpha ratio), and the amplitude and frequency of the "AF" region. Significant differences between the groups, in both levels, were observed for SFF and L1-L0, with actresses presenting lower values. There were no significant differences between groups for Leq or alpha ratio at either level. There was no evidence of an "AF" cluster in the actresses' voices. Voice projection for this group of actresses seemed to be mainly a result of a laryngeal setting instead of vocal tract resonances., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Background: White matter changes (WMC) are related to cognitive deficits and dementia. Our aim was to determine the extent to which the performance in neuropsychological tests would be able to predict the clinical diagnosis of dementia., Methods: The LADIS (Leukoaraiosis and Disability) is a prospective study that evaluates the impact of WMC on the transition of independent elderly to disability. The subjects were evaluated at baseline and yearly during 3 years with a comprehensive clinical, functional and neuropsychological protocol. At each visit, dementia was classified according to clinical criteria. The performance in the neuropsychological batteries was compared according to the clinical diagnosis of dementia., Results: From the initially enrolled 639 subjects, 480 were evaluated at year 3. Dementia was diagnosed in 90 participants. The demented subjects had worse performance in almost all the baseline cognitive tests. Using receiver operating characteristic curves, we found that the Vascular Dementia Assessment Scale (VADAS) battery had higher sensitivity and specificity rates (area under the curve = 82%) to identify dementia compared with the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale. Worse performance on baseline MMSE (beta = 0.33; p < 0.001) and VADAS (beta = -0.07; p = 0.02) were predictors of dementia (regression analyses)., Conclusion: Performance on the MMSE and the VADAS battery were important predictors of dementia at a 3-year period., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions., Methods: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models., Results: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy., Conclusions: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function., (Copyright 2009 S. Karger AG, Basel.)

Background: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML., Methods: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65-84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524)., Results: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory., Conclusion: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions., (Copyright 2009 S. Karger AG, Basel.)