Catarina Santos

White matter changes and diabetes predict cognitive decline in the elderly The LADIS Study

Objective: We aimed to study if age-related white matter changes (WMC) and vascular risk factors were predictors of cognitive decline in elderly subjects with WMC living independently. Methods: The Leukoaraiosis and Disability prospective multinational European study (LADIS) evaluates the impact of WMC on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Additionally, dementia, subtypes of dementia, and cognitive decline without dementia were classified according to usual clinical criteria. MRI was performed at entry and at the end of the study. Results: A total of 639 subjects were included (74.1 ± 5 years, 55% women, 9.6 ± 3.8 years of schooling). At end of follow-up, 90 patients had dementia and 147 had cognitive impairment no dementia. Using Cox regression analysis, WMC severity independently predicted cognitive decline (dementia and not dementia), independently of age, education, and medial temporal atrophy (MTA). Diabetes at baseline was the only vascular risk factor that independently predicted cognitive decline during follow-up, controlling for age, education, WMC severity, and temporal atrophy. Considering subtypes of dementia, Alzheimer disease (AD) was predicted only by MTA, while vascular dementia was predicted by previous stroke, WMC severity, and MTA. Conclusion: WMC severity and diabetes are independent predictors of cognitive decline in an initially nondisabled elderly population. Vascular dementia is predicted by previous stroke and WMC, while AD is predicted only by MTA.

Poststroke Emotional and Behavior Impairment: A Narrative Review

Emotional and behavioral disturbances are a frequent complication in stroke survivors. They are underdiagnosed, have a high impact on quality of life and are often a precipitant of institutionalization. For the caregivers of stroke survivors, these disturbances are a main cause of exhaustion. Health professionals have an insufficient training in their diagnosis and management which demands qualified skills and dedication of a multiprofessional team. In this article, we update some of the most common or relevant poststroke emotional and behavioral disturbances, including poststroke mania and poststroke depression, poststroke anxiety disorders, posttraumatic stress disorder, personality changes with focus on apathy and disturbances of emotional expression control. Significant advances in the management of poststroke emotional and behavioral disturbances will need the use of comparable instruments and methods and multicenter collaboration.

Mania and Stroke: A Systematic Review

Background: Mania is a rare consequence of stroke and according to the sparse published information it is difficult to describe its demographic, clinical and prognostic characteristics. Methods: We performed a systematic review of all cases of mania and stroke to describe those characteristics. Studies were identified from comprehensive searches of electronic databases, reference lists of the studies collected and handbooks. Two authors independently assessed abstracts, and collected and extracted data. Results: From 265 abstracts, 139 were potentially relevant. For the first analysis, which tries to answer the clinical question of the relationship between mania and stroke, 49 studies met the inclusion criteria and described 74 cases. For the second analysis, we looked for an explicit temporal and causal relationship between manic symptoms and stroke, and selected 32 studies describing 49 cases. In both analyses, the typical patient was male, without a personal or family history of psychiatric disorder, with at least one vascular risk factor, but without subcortical atrophy and had suffered a right cerebral infarct. The majority of patients (92%) presented elevated mood as the first symptom. The other frequent symptoms were an increased rate or amount of speech (71%), insomnia (69%) and agitation (63%). Conclusions: Post-stroke mania should be considered in any manic patient who presents concomitant neurological focal deficits and is older than expected for the onset of primary mania. The results of a systematic study of mania in acute stroke with subsequent follow-up and data from diffusion MR or perfusion CT in a multicenter study with a central database would be relevant.

Anger, hostility and aggression in the first days of acute stroke

In acute stroke patients, anger can disturb management and rehabilitation and creates a stressful situation for family, health‐care providers and other patients. We aim to describe the presence of anger and its association with demographic, clinical, psychiatric, lesion variables and functional outcome in acute stroke patients. We screened anger prospectively in 202 consecutive acute stroke patients (≤4 days) using eight items from three psychiatric scales (Catastrophic Reaction Scale, Mania Rating Scale and Comprehensive Psychopathological Rating Scale). Anger was present if the patient scored in at least one item. Anger was detected in 71 (35%) patients and 26 of these were severely angry (≥4 points). There was no association between anger and the considered variables. Analysis of the items extracted two factors: (i) the emotional‐cognitive and (ii) the behavioural components of anger. These components were independent of each other in 26 patients. In 38 patients we found a dissociation between clinical observation and patients’ subjective expression. Anger was frequent in acute stroke patients. Anger was probably triggered by the brain lesion, which interfered with the emotional control. The lack of an association with clinical and imaging variables suggests a contribution of psychological/psychosocial dimensions.

Neuropsychiatric disturbances in acute subarachnoid haemorrhage

Background:  Acute and unexpected neuropsychiatric disturbances can herald subarachnoid haemorrhage (SAH). We investigated the risk factors for neuropsychiatric disturbances in acute SAH and analysed the relation between neuropsychiatric disturbances and location and amount of haematic densities and hydrocephalus.

Self-perceived memory complaints predict progression to Alzheimer disease: The LADIS study.

Memory complaints are frequent in the elderly but its implications in cognition over time remain a controversial issue. Our objective was to evaluate the risk of self perceived memory complaints in the evolution for future dementia. The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes (WMC) on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Dementia and subtypes of dementia were classified. Self perceived memory complaints in independent elderly were collected during the interview. MRI was performed at entry and at the end of the study. 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). At end of follow-up, 90 patients were demented (vascular dementia, 54; Alzheimers disease (AD) and AD with vascular component, 34; frontotemporal dementia, 2). Using Cox regression analysis, we found that self perceived memory complaints were a strong predictor of AD and AD with vascular component during the follow-up (β = 2.7, p = 0.008; HR = 15.5, CI 95% [2.04, 117.6]), independently of other confounders, namely depressive symptoms, WMC severity, medial temporal lobe atrophy, and global cognition status at baseline. Self perceived memory complaints did not predict vascular dementia. In the LADIS study, self perceived memory complaints predicted AD but not vascular dementia in elderly subjects with WMC living independently.

Denial in the first days of acute stroke

Denial is a disorder of self-awareness that is frequent after acute stroke, with potential negative influence in the care of patients. The aim of this study was to describe the presence and correlates of denial in acute stroke.We assessed denial in a sample of 180 consecutive acute stroke patients (≤4 days) and in a control group of 50 acute coronary patients using the Denial of Illness Scale (DIS).41% (74) acute stroke patients (mean DIS score=4.1, SD=2.2, range 0 to 10) and 24% (12) acute coronary patients (mean DIS score=3.2, SD=1.5, range 0 to 10) presented denial (χ2=4.19, p=.04; U=3405.50, p=.01). Denial was more frequent and severe in patients with lower educational level (χ2= 5.04, p=.04; U=2110.50; p=.01), neglect (χ2= 21.38, p=.00; U=1130.50; p=.00), cognitive impairment (χ2= 6.27, p=.02; U=1181.50; p=.01) and after hemispherical lesions (χ2=4.68, p=.05; U=1982.50; p=.04). In logistic regression low educational level, neglect and cognitive impairment were independent factors predicting denial in stroke patients (R2= 21%). Patients with denial can express depressive symptoms. Patients with denial had a worse outcome at discharge (χ2=4.91, p=.04; U=2918.00; p=.03).Denial is a frequent phenomenon after acute stroke. We propose that there is a multifactorial model for the emergence of denial, lower educational as a predisposing condition, and acute stroke due to hemisphere lesion and causing neglect and cognitive impairment as precipitating events. All these factors limit patients’ assessment of their condition and body functions.

Seahorses under a changing ocean: the impact of warming and acidification on the behaviour and physiology of a poor-swimming bony-armoured fish

Many seahorse species are already threatened worldwide, and we do not know how they will endure an additional threat as climate change. Our results show that adult seahorses (Hippocampus guttulatus) seem to be relatively well prepared to face future changes in ocean temperature, but not the combined effect of warming and acidification.

Biodistribution of a 67Ga-labeled anti-TNF VHH single-domain antibody containing a bacterial albumin-binding domain (Zag)

INTRODUCTION Small domain antibodies (sdAbs) present high potential for both molecular in vivo imaging and therapy. Owing to the low molecular weight they are rapidly cleared from blood circulation, and new strategies to extend their half-lifes are needed for therapeutic applications. We have selected a bacterial albumin-binding domain (ABD) from protein Zag to be fused to an anti-tumor necrosis factor (TNF) single variable-domain heavy-chain region antibody (VHH) to delay blood clearance, and evaluated the biodistribution profile of the fusion protein. METHODS The anti-TNF VHH and the fusion protein VHH-Zag were conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA). The anti-TNF and albumin-binding properties of the conjugates NOTA-VHH and NOTA-VHH-Zag were assessed by enzyme-linked immunosorbent assay (ELISA). The radioconjugates (67)Ga-NOTA-VHH and (67)Ga-NOTA-VHH-Zag were obtained by reaction of (67)GaCl3 with the corresponding conjugates at room temperature. Biodistribution studies were performed in healthy female CD-1 mice. RESULTS The immunoreactivity of the VHH-based proteins is preserved upon conjugation to NOTA as well as after radiometallation. The radiochemical purity of the radioconjugates was higher than 95% as determined by ITLC-SG after purification by gel filtration. The biodistribution studies showed that the Zag domain affected the pharmacokinetic properties of VHH, with impressive differences in blood clearance (0.028 ± 0.004 vs 1.7 ± 0.8 % I.A./g) and total excretion (97.8 ± 0.6 vs 25.5 ± 2.1 % I.A.) for (67)Ga-NOTA-VHH and (67)Ga-NOTA-VHH-Zag, respectively, at 24h p.i. CONCLUSION The Zag domain prolonged the circulation time of VHH by reducing the blood clearance of the labeled fusion protein (67)Ga-NOTA-VHH-Zag. In this way, the anti-TNF VHH in fusion with the Zag ABD presents a higher therapeutic potential than the unmodified VHH.

Cuttlefish capsule: an effective shield against contaminants in the wild

Increasing anthropogenic pressures in estuaries are responsible for the rise of contaminants in several compartments of these ecosystems. Species that benefit from the nursery services provided by estuaries are exposed to such contaminants (e.g. metals and metalloids). It is therefore relevant to understand if marine invertebrates that use these areas as spawning grounds accumulate contaminants in their tissues throughout embryogenesis. This study aimed to quantify As, Co, Cr, Cu, Mn, Ni, Se, Pb, V and Zn concentrations in both capsule and embryos of the common cuttlefish (Sepia officinalis) in Sado Estuary (Portugal). Moreover, embryos at their initial, intermediate and final stage of development were collected in sites subjected to different anthropogenic pressures. In general, the capsule accumulated higher element concentration throughout embryogenesis which indicates that the capsule acts as an effective barrier against contaminants uptake by the embryo. Although the capsule becomes thinner throughout embryogenesis, embryos protection does not seem to be compromised at later development stages. Additionally, the higher concentrations of As, Cu, Se and Zn in the embryo in comparison to the capsule suggests important biological roles during the embryogenesis of this cephalopod mollusc.