Lithium, a Treatment Option for Alzheimer's Disease? A Review of Existing Evidence and Discussion on Future Perspectives.

After over 50 years of use, lithium-salts remain the first-line therapy for the management of bipolar disorder. Throughout this period, the potential for lithium salts has been extensively studied and numerous data favor its use in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD). We reviewed existing evidence gathered from clinical case reports and studies on the effect of lithium on neuropsychological symptoms of AD and as a disease-modifying treatment acting on cognitive symptoms. The review summarizes the molecular pathways, involving GSK-3ß inhibition and neuroprotection, through which lithium is proposed to exert its effect. Limitations to its current use in AD are discussed and future perspectives as a potential treatment option for AD are considered in regard to ongoing clinical trials using different forms of lithium.

Single-mutations at the galactose-binding site of enzymes GalK, GalU, and LgtC enable the efficient synthesis of UDP-6-azido-6-deoxy-d-galactose and azido-functionalized Gb3 analogs.

Lysosomal accumulation of the glycosphingolipid globotriaosylceramide Gb3 is linked to the deficient activity of the α-galactosidase A in the Anderson-Fabry disease and an elevated level of deacylated Gb3 is a hallmark of this condition. Localization of Gb3 in the plasma membrane is critical for studying how the membrane organization and its dynamics are affected in this genetic disorder. Gb3 analogs containing a terminal 6-azido-functionalized galactose in its head group globotriose (αGal1, 4ßGal1, and 4Glc) are attractive chemical reporters for bioimaging, as the azido-group may act as a chemical tag for bio-orthogonal click chemistry. We report here the production of azido-Gb3 analogs employing mutants of galactokinase, UTP-glucose-1-phosphate uridylyltransferase, and α-1,4-galactosyltransferase LgtC, which participate in the synthesis of the sugar motif globotriose. Variants of enzymes galactokinase/UTP-glucose-1-phosphate uridylyltransferase generate UDP-6-azido-6-deoxy-d-galactose, which is the galactosyl-donor used by LgtC for transferring the terminal galactose moiety to lactosyl-acceptors. Residues at the galactose-binding site of the 3 enzymes were modified to facilitate the accommodation of azido-functionalized substrates and variants outperforming the wild-type enzymes were characterized. Synthesis of 6-azido-6-deoxy-d-galactose-1-phosphate, UDP-6-azido-6-deoxy-d-galactose, and azido-Gb3 analogs by variants GalK-E37S, GalU-D133V, and LgtC-Q187S, respectively, is 3-6-fold that of their wild-type counterparts. Coupled reactions with these variants permit the production of the pricy, unnatural galactosyl-donor UDP-6-azido-6-deoxy-d-galactose with ~90% conversion yields, and products azido-globotriose and lyso-AzGb3 with substrate conversion of up to 70%. AzGb3 analogs could serve as precursors for the synthesis of other tagged glycosphingolipids of the globo-series.

Giant aneurysm of the right coronary artery, report of a case and review of the literature.

Coronary artery aneurysms are described as a localized dilatation that exceeds the normal diameter by 1.5 times. This is a rare condition; its incidence varies from 0.3% up to 5.3% of all coronary angiographies. Those aneurysms that exceed 4 times the diameter of a normal artery are considered giant aneurysms, which are even more uncommon, presenting between 0.02% and 0.2% of all cases. There is controversy regarding its pathophysiology, however, up to 50% of the cases are related to atherosclerosis. They are diagnosed more frequently between the sixth and seventh decade of life. The main clinical manifestations are related to ischemic heart disease. Regarding their treatment, there is no general consensus towards its management in adult patients. The options are medical, surgical or percutaneous treatment. We report the presence of a giant aneurysm of the right coronary artery and giant ectasia of the left coronary system with active thrombosis in a man with history of an abdominal aortic aneurysm, with endovascular treatment and a non-ST segment elevation myocardial infarction with no reperfusion strategy, who required a coronary computed tomography, identifying the anatomical characteristics of this disease.

Los aneurismas de las arterias coronarias se definen como una dilatación localizada que excede el diámetro normal en 1.5 veces. Esta es una condición poco frecuente, su incidencia varía del 0.3 hasta el 5.3% de las angiografías coronarias. Los aneurismas que exceden cuatro veces el diámetro del vaso normal se consideran gigantes. Estos son aún más raros y se presentan en el 0.02 a 0.2% de todos los casos. Existe controversia en cuanto a su fisiopatología, sin embargo, hasta el 50% de los casos se relacionan con la aterosclerosis. Se diagnostican más frecuentemente entre la sexta y séptima décadas de vida. Las principales manifestaciones clínicas están relacionadas con la cardiopatía isquémica. Respecto a su tratamiento, no existe un consenso del manejo en los pacientes adultos, las opciones son: médico, quirúrgico o intervencionismo. Reportamos la presencia de un aneurisma gigante de la coronaria derecha y ectasia gigante del sistema izquierdo con trombosis activa en un hombre con antecedentes de un aneurisma en la aorta abdominal, tratado por vía endovascular, e infarto agudo al miocardio sin elevación del segmento ST no reperfundido. Requirió de estudio de angiotomografía coronaria, el cual permitió la identificación de las características anatómicas de esta enfermedad.

Aneurisma gigante de la arteria coronaria derecha, reporte de un caso y revisión de la literatura / Giant aneurysm of the right coronary artery, report of a case and review of the literature

Resumen Los aneurismas de las arterias coronarias se definen como una dilatación localizada que excede el diámetro normal en 1.5 veces. Esta es una condición poco frecuente, su incidencia varía del 0.3 hasta el 5.3% de las angiografías coronarias. Los aneurismas que exceden cuatro veces el diámetro del vaso normal se consideran gigantes. Estos son aún más raros y se presentan en el 0.02 a 0.2% de todos los casos. Existe controversia en cuanto a su fisiopatología, sin embargo, hasta el 50% de los casos se relacionan con la aterosclerosis. Se diagnostican más frecuentemente entre la sexta y séptima décadas de vida. Las principales manifestaciones clínicas están relacionadas con la cardiopatía isquémica. Respecto a su tratamiento, no existe un consenso del manejo en los pacientes adultos, las opciones son: médico, quirúrgico o intervencionismo. Reportamos la presencia de un aneurisma gigante de la coronaria derecha y ectasia gigante del sistema izquierdo con trombosis activa en un hombre con antecedentes de un aneurisma en la aorta abdominal, tratado por vía endovascular, e infarto agudo al miocardio sin elevación del segmento ST no reperfundido. Requirió de estudio de angiotomografía coronaria, el cual permitió la identificación de las características anatómicas de esta enfermedad.

Abstract Coronary artery aneurysms are described as a localized dilatation that exceeds the normal diameter by 1.5 times. This is a rare condition; its incidence varies from 0.3% up to 5.3% of all coronary angiographies. Those aneurysms that exceed 4 times the diameter of a normal artery are considered giant aneurysms, which are even more uncommon, presenting between 0.02% and 0.2% of all cases. There is controversy regarding its pathophysiology, however, up to 50% of the cases are related to atherosclerosis. They are diagnosed more frequently between the sixth and seventh decade of life. The main clinical manifestations are related to ischemic heart disease. Regarding their treatment, there is no general consensus towards its management in adult patients. The options are medical, surgical or percutaneous treatment. We report the presence of a giant aneurysm of the right coronary artery and giant ectasia of the left coronary system with active thrombosis in a man with history of an abdominal aortic aneurysm, with endovascular treatment and a non-ST segment elevation myocardial infarction with no reperfusion strategy, who required a coronary computed tomography, identifying the anatomical characteristics of this disease.

Zwitterion-Functionalized Detonation Nanodiamond with Superior Protein Repulsion and Colloidal Stability in Physiological Media.

Nanodiamond (ND) is a versatile and promising material for bioapplications. Despite many efforts, agglomeration of nanodiamond and the nonspecific adsorption of proteins on the ND surface when exposed to biofluids remains a major obstacle for biomedical applications. Here, the functionalization of detonation nanodiamond with zwitterionic moieties in combination with tetraethylene glycol (TEG) moieties immobilized by click chemistry to improve the colloidal dispersion in physiological media with strong ion background and for the simultaneous prevention of nonspecific interactions with proteins is reported. Based on five building blocks, a series of ND conjugates is synthesized and their performance is compared in biofluids, such as fetal bovine serum (FBS) and Dulbecco's modified Eagle medium (DMEM). The adsorption of proteins is investigated via dynamic light scattering (DLS) and thermogravimetric analysis. The colloidal stability is tested with DLS monitoring over prolonged periods of time in various ratios of water/FBS/DMEM and at different pH values. The results show that zwitterions efficiently promote the anti-fouling properties, whereas the TEG linker is essential for the enhanced colloidal stability of the particles.

Giant aneurysm of the right coronary artery, report of a case and review of the literature.

Coronary artery aneurysms are described as a localized dilatation that exceeds the normal diameter by 1.5 times. This is a rare condition; its incidence varies from 0.3% up to 5.3% of all coronary angiographies. Those aneurysms that exceed 4 times the diameter of a normal artery are considered giant aneurysms, which are even more uncommon, presenting between 0.02% and 0.2% of all cases. There is controversy regarding its pathophysiology, however, up to 50% of the cases are related to atherosclerosis. They are diagnosed more frequently between the sixth and seventh decade of life. The main clinical manifestations are related to ischemic heart disease. Regarding their treatment, there is no general consensus toward its management in adult patients. The options are medical, surgical, or percutaneous treatment. We report the presence of a giant aneurysm of the right coronary artery and giant ectasia of the left coronary system with active thrombosis in a man with a history of an abdominal aortic aneurysm, with endovascular treatment and a non-ST segment elevation myocardial infarction with no reperfusion strategy, who required a coronary computed tomography, identifying the anatomical characteristics of this disease.

Los aneurismas de las arterias coronarias se definen como una dilatación localizada que excede el diámetro normal en 1.5 veces. Esta es una condición poco frecuente, su incidencia varía del 0.3 hasta el 5.3% de las angiografías coronarias. Los aneurismas que exceden cuatro veces el diámetro del vaso normal se consideran gigantes. Estos son aún más raros y se presentan en el 0.02 a 0.2% de todos los casos. Existe controversia en cuanto a su fisiopatología, sin embargo, hasta el 50% de los casos se relacionan con la aterosclerosis. Se diagnostican más frecuentemente entre la sexta y séptima décadas de vida. Las principales manifestaciones clínicas están relacionadas con la cardiopatía isquémica. Respecto a su tratamiento, no existe un consenso del manejo en los pacientes adultos, las opciones son: médico, quirúrgico o intervencionismo. Reportamos la presencia de un aneurisma gigante de la coronaria derecha y ectasia gigante del sistema izquierdo con trombosis activa en un hombre con antecedentes de un aneurisma en la aorta abdominal, tratado por vía endovascular, e infarto agudo al miocardio sin elevación del segmento ST no reperfundido. Requirió de estudio de angiotomografía coronaria, el cual permitió la identificación de las características anatómicas de esta enfermedad.

The Evaluation of Flow-Mediated Vasodilation in the Brachial Artery Correlates With Endothelial Dysfunction Evaluated by Nitric Oxide Synthase Metabolites in Marfan Syndrome Patients.

Marfan syndrome (MS) is of the most common connective tissue disorders. Although most patients have mutations in the fibrillin-1 gene (FBN1) and more than 1,700 mutations have been described, there are no mutations in less than 10% of patients. Aortic dilation is the most important complication; it involves chronic inflammatory processes and endothelial dysfunction. Prospective study from March 2015 to January 2017, in a cohort of 32 patients of MS confirmed by Ghent criteria and 35 controls of both genders, with a median age of 26 years (18-56). Patients had no comorbidities such as diabetes, hypertension, and/or neoplasms. They were not being treated with statin, NSAIDs, calcium antagonists, oral nitrates, and/or beta-blockers during 7 days prior to the study and patients with smoking history in the last 4 years. Controls were matched by age and gender. We analyzed endothelial dysfunction by flow-mediated vasodilation in the brachial artery, determining the maximum peak flow in the reactive hyperemia phase with a Philips Envisor device with Doppler capability. Its correlation with serum levels of biological markers that could participate in endothelial dysfunction pathways such as NO3-/NO2- ratio, NO2- , citrulline, TNFα, IL-1, IL-6, IL-10, IL-8, osteopontin, ICAM, VCAM, and NO3-/NO2- was determined. Endothelial dysfunction was found in 21 MS patients (65%). The aortic annulus (AAo) was of 27 mm (22-40) and 24 mm (22-30) (p = 0.04) in MS patients with and without dysfunction. The level of NO3-/NO2- ratio, was of 108.95 ± 12.05 nM/ml in controls vs. 170.04 ± 18.76 nM/ml in MS (p = 0.002), NO2- was of 33.78 ± 3.41 vs. 43.95 ± 2.59 nM/ml (p = 0.03), citrulline 62.65 ± 3.46 vs. 72.81 ± 4.35 µMol/ml (p = 0.06). VCAM median was 39 pg/ml (0-86) vs. 32 pg/ml (11-66) (p = 0.03), respectively. The correlation of VCAM with triglycerides (TG) was of 0.62 (p = 0.005). There were no differences in TNFα, IL-1, IL-6, IL-8, IL-10, and osteopontin. MS endothelial dysfunction is related to aortic diameters, and increased levels of VCAM, L-citrulline and NO3-/NO2- ratio, NO2- . VCAM-1 has a significant correlation with TG and could play a significant role in endothelial dysfunction.

Participation of Arachidonic Acid Metabolism in the Aortic Aneurysm Formation in Patients with Marfan Syndrome.

Marfan syndrome (MFS) is a pleiotropic genetic disease involving the cardiovascular system where a fibrillin-1 mutation is present. This mutation is associated with accelerated activation of transforming growth factor ß (TGFß1) which contributes to the formation of aneurysms in the root of the aorta. There is an imbalance in the synthesis of thromboxane A2 (TXA2) and prostacyclin, that is a consequence of a differential protein expression of the isoforms of cyclooxygenases (COXs), suggesting an alteration of arachidonic acid (AA) metabolism. The aim of this study was to analyze the participation of AA metabolism associated with inflammatory factors in the dilation and dissection of the aortic aneurysm in patients with MFS. A decrease in AA (p = 0.02), an increase in oleic acid (OA), TGFß1, tumor necrosis factor alpha (TNFα), prostaglandin E2 (PGE2) (p < 0.05), and COXs activity (p = 0.002) was found. The expressions of phospholipase A2 (PLA2), cytochrome P450 (CYP450 4A), 5-lipoxygenase (5-LOX), COX2 and TXA2R (p < 0.05) showed a significant increase in the aortic aneurysm of patients with MFS compared to control subjects. COX1, 6-keto-prostaglandin 1 alpha (6-keto-PG1α) and 8-isoprostane did not show significant changes. Histological examination of the aortas showed an increase of cystic necrosis, elastic fibers and collagen in MFS. The results suggest that there are inflammatory factors coupled to genetic factors that predispose to aortic endothelial dysfunction in the aortic tissue of patients with MFS. There is a decrease in the percentage of AA, associated with an increase of PLA2, COX2/TXA2R, CYP450 4A, and 5-LOX which leads to a greater synthesis of PGE2 than of 6-keto-PGF1α, thus contributing to the formation of the aortic aneurysm. The evident loss of the homeostasis in these mechanisms confirms that there is a participation of the AA pathway in the aneurysm progression in MFS.

Costs of Care of Agitation Associated With Dementia in 8 European Countries: Results From the RightTimePlaceCare Study.

OBJECTIVE: To estimate the additional societal costs for people living with dementia (PwD) with agitation in home care (HC) and institutional long-term care (ILTC) settings in 8 European countries. DESIGN: Cross-sectional data from the RightTimePlaceCare cohort. SETTING: HC and ILTC settings from 8 European countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden, and England). PARTICIPANTS: A total of 1997 PwD (1217 in HC group and 780 lived in an ILTC) and their caregivers. MAIN OUTCOME MEASURES: Medical care, community care, and informal care were recorded using the Resource Utilization in Dementia (RUD) questionnaire. Agitation was assessed based on the agitation symptoms cluster defined by the presence of agitation and/or irritability and/or disinhibition and/or aberrant motor behavior items of the Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: Total monthly mean cost differences due to agitation were 445€ in the HC setting and 561€ in the ILTC setting (P = .01 and .02, respectively). Informal care costs were the main driver in the HC group (73% of total costs) and institutional care costs were the main driver in the ILTC group (53% of total costs). After adjustments, the log link generalized linear mixed model showed an association between agitation symptoms and an increase of informal care costs by 17% per month in HC setting (P < .05). CONCLUSION: This study found that agitation symptoms have a substantial impact on informal care costs in the community care setting. Future research is needed to evaluate which strategies may be efficient by improving the cost-effectiveness ratio and reducing the burden associated with informal care in the management of agitation in PwD.

Caring for a Person With Dementia on the Margins of Long-Term Care: A Perspective on Burden From 8 European Countries.

OBJECTIVES: To explore associations between carer burden and characteristics of (1) the informal carer, (2) the person with dementia, and (3) the care support network in 8 European countries. DESIGN: Cross-sectional study. SETTING: People with dementia judged at risk of admission to long-term care (LTC) facilities in 8 European countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden, United Kingdom). PARTICIPANTS: A total of 1223 people with dementia supported by community services at home or receiving day care or respite care and their informal carers. MEASUREMENTS: Variables regarding the informal carer included familial relationship and living situation. Variables relating to the person with dementia included cognitive functioning (S-MMSE), neuropsychiatric symptoms (NPI-Q), depressive symptoms (Cornell depression scale), comorbidity (Charlson Comorbidity Index), and physical functioning (Katz Activity of Daily Living [ADL] Index). The care support network was measured using hours of caregiving (ADLs, instrumental ADLs [IADLs], supervision), additional informal care support, and service receipt (home care, day care). Experience of carer burden was recorded using the Zarit Burden Interview. Logistic regression analysis was used to determine factors associated with high carer burden. RESULTS: Carer burden was highest in Estonia (mean 39.7/88) and lowest in the Netherlands (mean 26.5/88). High burden was significantly associated with characteristics of the informal carer (family relationship, specifically wives or daughters), of the person with dementia (physical dependency in ADLs; neuropsychiatric symptoms, in particular nighttime behaviors and irritability), the care support network (hours of caregiving supervision; receipt of other informal care support) and country of residence. CONCLUSION: A range of factors are associated with burden in informal carers of people with dementia judged to be on the margins of LTC. Support for informal carers needs to take account of gender differences. The dual challenges of distressed behaviors and difficulties in ADLs by the person with dementia may be addressed by specific nonpharmacological interventions focusing on both elements. The potential protective effect of additional informal support to carers highlights the importance of peer support or better targeted home support services. The implementation of appropriate and tailored interventions to reduce burden by supporting informal carers may enable people with dementia to remain at home for longer.

Refining Mild-to-Moderate Alzheimer Disease Screening: A Tool for Clinicians.

OBJECTIVES: Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population. DESIGN: Data were obtained from two independent, longitudinal, observational multicenter studies in patients with mild-to-moderate AD. SETTING: The two studies were the European "Impact of Cholinergic Treatment Use" (ICTUS) and the French "REseau sur la maladie d'Alzheimer FRançais" (REAL.FR). PARTICIPANTS: We used prospective data of 756 patients enrolled in ICTUS and 340 enrolled in REAL.FR. MEASUREMENTS: A prediction rule of cognitive decline was derived on ICTUS using classification and regression tree analysis and then cross-validated on REAL.FR. A range of demographic, clinical and cognitive variables were tested as predictor variables. RESULTS: Overall, 27.9% of patients in ICTUS and 20.9% in REAL.FR did not decline over 2 years. We identified optimized cut-points on the verbal memory items of the Alzheimer Disease Assessment Scale-Cognitive Subscale capable of classifying patients at baseline into those who went on to decline and those who remained stable or improved over the duration of the trial. CONCLUSION: The application of this simple rule would allow the identification of dementia cases where a more detailed differential diagnostic examination (eg, with biomarkers) is warranted. These findings are promising toward the refinement of AD screening in the clinic. For a further optimization of our classification rule, we encourage others to use our methodological approach on other episodic memory assessment tools designed to detect even small cognitive changes in patients with AD.

Frailty Index and Cognitive Decline in Alzheimer's Disease: Data from the Impact of Cholinergic Treatment USe Study.

OBJECTIVES: To determine whether the Frailty Index (FI) was associated with short-term cognitive decline (according to changes in Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores at 1-year follow-up) in individuals with Alzheimer's disease (AD). DESIGN: Prospective cohort study. SETTING: Impact of Cholinergic Treatment USe study. PARTICIPANTS: Individuals with mild-to-moderate AD (N = 973). MEASUREMENTS: Severity of dementia was assessed using the Clinical Dementia Rating (CDR). FI was calculated as the ratio of actual to potential deficits (deficits present divided by 30). Linear regression analyses were performed and stratified according to severity of dementia. RESULTS: A 1-unit (0.033 points) increase in FI corresponded to significant and clinically relevant cognitive decline, after adjustments for age, sex, and years of education (0.63-4.63 points on the MMSE, P = .01; 2.87-11.1 points on the ADAS-Cog, P = .001) after 1 year of follow-up. Differences in changes in MMSE and ADAS-Cog scores between nonfrail and frail individuals were 0.67 and 1.6 points, respectively. Although statistically significant, the clinical relevance of this finding remains to be further investigated. CONCLUSION: The FI may be a promising instrument for the assessment of the vulnerability of individuals with AD. Its implementation in clinical practice may support clinical decisions by identifying individuals at high risk of negative outcomes, specifically, short-term cognitive decline.

What Makes Institutional Long-Term Care the Most Appropriate Setting for People With Dementia? Exploring the Influence of Client Characteristics, Decision-Maker Attributes, and Country in 8 European Nations.

OBJECTIVES: To explore the extent to which client characteristics, decision-maker attributes, and country influence judgments of institutional long-term care (ILTC) appropriateness for people with dementia. DESIGN, SETTING, AND PARTICIPANTS: A total of 161 experts in dementia care from 8 European countries reviewed a series of 14 vignettes representing people with dementia on the cusp of ILTC admission and indicated the most appropriate setting in which to support each case in a simple discrete choice exercise: own home, very sheltered housing, residential home, or nursing home. At least 16 experts participated in each country (Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the United Kingdom). MEASUREMENTS: Descriptive statistics were used to characterize the experts and their placement preferences. Logistic regression modeling was used to explore the extent to which the sociodemographic and clinical characteristics of people with dementia, and the profession, workplace, and country of decision-makers were associated with ILTC recommendation. RESULTS: Client characteristics, decision-maker attributes, and country all seemed to play a part in influencing professionals' perceptions of the appropriateness of ILTC for people with dementia. Expert decision-makers were more likely to recommend ILTC for individuals who required help with mobility or had multiple care needs, and appeared to give more weight to carers' than clients' wishes. Community-based social workers were less likely than other professional groups to favor ILTC placement. Experts in Finland, Germany, and the United Kingdom were less likely to recommend ILTC than experts in France, the Netherlands, and Estonia; experts in Sweden and Spain took an intermediate position. CONCLUSION: This study provides new understanding of the factors that shape professionals' perceptions of ILTC appropriateness and highlights the need to construct multifaceted models of institutionalization when planning services for people with dementia. It also has several important clinical implications (including flagging interventions that could decrease the need for ILTC), and provides a basis for enhancing professionals' decision-making capabilities (including the greater involvement of clients themselves).

Inter-country exploration of factors associated with admission to long-term institutional dementia care: evidence from the RightTimePlaceCare study.

AIM: To explore inter-country variation of factors associated with institutionalization of people with dementia. BACKGROUND: There is an urgent need for evidence on whether factors associated with admission to institutional dementia care are applicable across healthcare systems, as increasing evidence suggests that these factors could be country-specific. DESIGN: A prospective cohort study. METHOD: Primary data were collected in eight European countries, at baseline and after 3 months follow-up (November 2010-April 2012). The sample included 2014 dyads of people with dementia and their informal caregivers; 791 patients were recently institutionalized, 1223 patients lived at home and were at risk of institutionalization. Associations between care setting (institution vs. home) and factors shown to influence institutionalization (e.g. cognition, independence in activities of daily life, behaviour) were studied. RESULTS: Considerable differences were found between the eight countries in characteristics of people with dementia who had been recently admitted to ILTC. However, caregiver burden appeared the most consistent factor associated with institutionalization in all analyses. Indications for the importance of independence in activities of daily life were found as well, although country differences may be more prominent for this factor. CONCLUSION: Evidence was found for two common factors, crucial in the process of institutionalization across countries: caregiver burden and independency in activities of daily life. However, this study also suggests that admission to institutional dementia care is context-specific, as wide variation exists in factors associated with institutionalization across countries. Tailored best-practice strategies are needed to reflect variations in response to these needs.

The association between positive-negative reactions of informal caregivers of people with dementia and health outcomes in eight European countries: a cross-sectional study.

AIM: To describe the associations between positive and negative reactions of informal caregivers of people with dementia and health outcomes across eight European Countries. BACKGROUND: Caring for someone with dementia may have implications for the caregiver's own health and for the care recipient. These consequences could be associated with caregivers' reactions to the process of care. DESIGN: Association study based on cross-sectional data. METHODS: Participants were people with dementia and their informal caregivers living at home or in long-term care institutions. Data were collected between November 2010-April 2012 using the Caregiver Reaction Assessment (with dimensions of self-esteem, lack of family support, financial problems, disrupted schedule and health problems) and associations were sought with informal caregiver burden, quality of life and psychological well-being and with dementia sufferers' neuropsychiatric symptoms, comorbidity and dependency in activities of daily living using correlation coefficients. RESULTS: Data from 2014 participants were used. Variability across countries was noted, as well as differences between care at home and in long-term care institutions. In general, self-esteem and lack of family support correlated with caregiver burden and psychological well-being. Associations were also found between disrupted schedule and caregiver burden, psychological well-being and quality of life. Health problems were clearly associated with caregiver burden, psychological well-being and quality of life. CONCLUSION: Study results support links between the reactions of informal caregivers of people with dementia and health outcomes. These may have implications in terms of how services are addressed.

Older persons with dementia at risk for institutionalization in eight European countries: a cross-sectional study on the perceptions of informal caregivers and healthcare professionals.

AIMS: To explore the perceptions of informal caregivers and healthcare professionals regarding potential reasons for the institutionalization of older persons with dementia in eight European countries. BACKGROUND: Healthcare professionals may have an important role in facilitating informal caregivers' decision-making regarding institutionalization. Little is known about the perceptions of informal caregivers and healthcare professionals prior to institutionalization. DESIGN: Cross-sectional survey in eight European countries (November 2010-January 2012). METHODS: Healthcare professionals reported why they clinically judged persons with dementia at risk for institutionalization. Informal caregivers reported potential reasons from their perspectives. Answers were openly coded and categorized. Variation between informal caregivers and healthcare professionals was investigated (agreement on at least one potential reason per case/proportion of maximum attainable kappa). RESULTS: Judgements of healthcare professionals and informal caregivers on 1160 persons with dementia were included. A total of 22 categories emerged. Approximately 90% of informal caregivers reported potential reasons. In 41% of the cases, informal caregivers and healthcare professionals agreed on at least one reason. Discrepancy was high for potential reasons related to caregiver burden. For the most frequent categories (caregiver burden, caregiver unable to provide care, neuropsychiatric symptoms, overall deterioration, care dependency), 24-41% of the attainable kappa was achieved. Differences between countries emerged indicating more favourable agreement in Finland, Sweden and Estonia and lowest agreement in England and Spain. CONCLUSION: Agreement between healthcare professionals and informal caregivers on potential reasons for institutionalization was low-to-moderate. Healthcare professionals are challenged to develop a detailed understanding of the perspectives and perceived burden of informal caregivers.

Predicting institutional long-term care admission in dementia: a mixed-methods study of informal caregivers' reports.

AIM: To investigate agreement between: (1) expected reasons and actual reasons for admission of people with dementia according to informal caregivers; (2) scores on measurement instruments prior to admission and the actual reasons for admission according to informal caregivers. BACKGROUND: Timely admission of people with dementia is a crucial issue. Information is highly warranted on whether informal caregivers are capable of prior identification of causes of admission and, can thus be considered a reliable prospective source on causes of admission. DESIGN: A cohort study among informal caregivers of people with dementia who made a transition to institutional long-term care. METHODS: Qualitative data on the expected and actual reasons for admission were collected via open-ended questions at baseline and follow-up. Furthermore, at baseline, data were collected using measurement instruments to measure pre-admission characteristics. Interviews took place between November 2010-April 2012. After categorizing the answers, the agreement between the expected and actual reasons was calculated. Furthermore, bivariate associations were calculated between the actual reasons for admission and scores on corresponding measurement instruments. RESULTS/FINDINGS: For most informal caregivers, there was agreement between their statements on the expected reason and the actual reason for admission. A third of the caregivers showed no conformity. Bivariate associations showed that there is also agreement between the actual reasons for admission and scores on corresponding measurement instruments. CONCLUSION: Informal caregivers can be considered reliable sources of information regarding what causes the admission of a person with dementia. Professional care should anticipate informal caregivers' statements and collaborate with them to strive for timely and appropriate admission.

Changes in caregiver burden and health-related quality of life of informal caregivers of older people with Dementia: evidence from the European RightTimePlaceCare prospective cohort study.

AIMS: To describe differences in caregiver burden and health-related quality of life of informal caregivers of people with dementia in eight European countries and assess changes after transition from home to institutional long-term care. BACKGROUND: Country differences in the experience of burden and health-related quality of life are rarely described. DESIGN: Prospective cohort study. METHODS: Data on burden and health-related quality of life were collected at baseline (conducted between November 2010-April 2012) and follow-up (after 3 months) using face-to-face interviews. Two groups of informal caregivers included those: (1) of people with dementia recently admitted to institutional long-term care facilities; and those (2) of people with dementia receiving home care. Statistical analyses focused on descriptive comparisons between groups and countries. RESULTS: Informal caregivers of about 2014 were interviewed. Informal caregivers of people with dementia at home experienced more burden compared with informal caregivers of recently institutionalised people with dementia. Almost no differences in health-related quality of life were found between groups. Large differences between countries on outcomes were found. Informal caregivers of people with dementia who made the transition to an institutional long-term care facility experienced a statistically significant decrease in burden and psychological distress at follow-up. CONCLUSION: Cross-country differences may be related to differences in health and social care systems. Taking this into account, informal caregiver interventions need to be tailored to (country specific) contexts and (individual) needs. Findings highlight the positive impact of admission to institutional long-term care on informal caregiver well-being.

Quality of life and quality of care for people with dementia receiving long term institutional care or professional home care: the European RightTimePlaceCare study.

OBJECTIVES: To explore how quality of life (QoL) and quality of care (QoC) for people with dementia (PwD) vary across 8 European countries; to explore how QoL and QoC for PwD vary across living arrangements; and to assess the association between QoL and QoC. DESIGN: Cross-sectional survey. SETTING: Institutional long term care and home care in 8 European countries (England, Estonia, Finland, France, Germany, the Netherlands, Spain, and Sweden). PARTICIPANTS: PwD receiving formal home care but at risk for admission to an institutional setting, and PwD who were recently admitted. MEASUREMENTS: QoL was assessed by the PwD and by their best informed proxies using the Quality of Life-Alzheimer's Disease scale (QoL-AD) (range 13-52). QoC was measured using quality of care indicators (eg, the presence of depressive symptoms, the presence of pressure ulcers). RESULTS: A total of 1123 PwD living at home (mean age 82.2, 63%women) and 791 PwD living in institutional care (mean age 84.1, 74% women) participated. QoL of PwD was most often rated highest in Sweden and England and lowest in Estonia and Spain. No differences in QoL were detected among the settings. For the QoC indicators, no consistent patterns were visible in such a way that certain countries or settings scored "higher" or "lower." The presence of depressive symptoms was most consistently associated with lower QoL (P ≤ .001). CONCLUSION: There is great variation in QoL and QoC scores among European countries and settings. To gain insight into the underlying causes of these differences, more knowledge is needed about the effect of different national health care systems and dementia strategies on QoL and QoC indicators. Depressive symptoms were associated with QoL, and executing longitudinal studies investigating which factors are associated with change in QoL is highly recommended.

Reasons for institutionalization of people with dementia: informal caregiver reports from 8 European countries.

OBJECTIVES: To explore reasons for institutionalization of people with dementia according to informal caregivers as well as variation in reasons between countries. DESIGN: An explorative cross-sectional study was conducted in 8 European countries. SETTING: Per country, a minimum of 3 long term care facilities, offering care and accommodation as a package, participated in this study. Participating countries were selected to represent different geographic areas in Europe. PARTICIPANTS: Of the 791 informal caregivers involved in the RightTimePlaceCare project of people with dementia who were recently admitted to a long term care facility, 786 were included for this study. MEASUREMENTS: As part of a semistructured interview, informal caregivers were asked the main reason for institutionalization in an open-ended question. Answers were categorized according to a conventional coding approach. All reasons were then quantified and tested. RESULTS: Mainly patient-related reasons were stated, such as neuropsychiatric symptoms (25%), care dependency (24%), and cognition (19%). Neuropsychiatric symptoms were among the most often mentioned reasons in most countries. Besides patient-related reasons, caregiver burden and the inability of the informal caregiver to care for the patient were stated as reasons (both 15%). Further analyses showed countries differ significantly in reasons according to informal caregivers. Additionally, reasons were analyzed for spouses and child-caregivers, showing that spouses more often stated reasons related to themselves compared with child-caregivers. CONCLUSION: Multiple reasons contribute to the institutionalization for people with dementia, with several factors that may influence why there were country differences. Variation in the organization of dementia care and cultural aspects, or the relationship between the informal caregiver and person with dementia may be factors influencing the reasons. Because of a wide variation in reasons between countries, no one-size-fits-all approach can be offered to guide informal caregivers when facing the possibility of institutionalization of the person with dementia.