The effect of external stimulation on functional networks in the aging healthy human brain.

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics.

Longitudinal effect of dementia carers' sense of coherence on burden.

BACKGROUND: A sense of coherence (SOC) could help us better understand why there are individuals who cope better than others in similar situations. The study aimed to assess the effect of SOC on the course of burden reports in relatives of persons with dementia. METHODS: This was a prospective cohort study of 156 dementia carers. The SOC was assessed by the Orientation to Life Questionnaire (OLQ-13), burden by Burden Interview, and personal and contextual characteristics were collected via ad hoc questions. The main dementia symptoms, including functional difficulties (Disability Assessment for Dementia), neuropsychiatric symptoms (Neuropsychiatric Inventory), and cognitive impairment (Mini-Mental State Examination), were also assessed. A general linear model was adjusted to determine the effect of SOC and other covariates on burden throughout the follow-up. Burden differences between baseline and 12 and 24 months were analysed, and the baseline OLQ-13 score was grouped by quartiles. RESULTS: The global burden reported increased after 24 months (F = 9.98; df = 2; p < 0.001), but not equally for all carers; daughters reported the greatest increase. SOC, functional disability, and neuropsychiatric disorders showed a significant effect on burden, but time did not. Carers with higher SOC at baseline tend to remain with lower burden levels, whereas carers with low SOC reported higher burden at each visit. CONCLUSIONS: This study reports evidence of the effect of SOC on burden at baseline, 12 and 24 months of follow-up. Burden scores differ by carers' SOC; those with higher SOC showed lower burden levels, whereas the low-SOC group reported a greater burden at each visit.

Whole-Brain Dynamics in Aging: Disruptions in Functional Connectivity and the Role of the Rich Club.

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50-64 years versus older group (n = 310); age range, 65-91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways.

BACKGROUND: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. METHODS: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. RESULTS: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor's bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient's mice. CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.

Changes in lifestyle resulting from confinement due to COVID-19 and depressive symptomatology: A cross-sectional a population-based study.

BACKGROUND: The measures adopted to control the spread of the COVID-19 pandemic in several countries included mobility and social restrictions that produced an immediate impact on the lifestyle of their inhabitants. METHODS: We assessed the association between the consequences of these measures and depressive symptomatology using a population-based sample of 692 individuals aged 18 or over from an ongoing study in the province of Girona (Catalonia, Spain). Participants responded to a telephone-based survey that included questions related to the consequences of confinement and the Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptomatology. Multivariate logistic and linear regressions were used to identify which changes in lifestyle resulting from confinement were independently associated with a possible depression episode and depressive symptomatology. RESULTS: The prevalence of a possible depressive episode during the confinement was 12.7% (95% CI = 10.3-15.4). An adverse work situation, expected economic distress, self-reported worsening of the mental health and of the dietary pattern, and worries about a relative's potential infection were variables related to an increased risk of having a possible depressive episode. The changes in lifestyle accounted for 32% of the variance of the PHQ-9 score. CONCLUSION: The findings indicate an association of the job situation, the expected negative economic consequences, the perceived worsening of health and habits, and the worries about COVID-19 infection with depressive symptomatology during the confinement.

Early parental death and psychosocial risk factors for dementia: A case-control study in Europe.

OBJECTIVES: To assess the association between early parental death and the risk of dementia in adult life and to examine the risk factors associated with early parental death in people with and without dementia. METHODS/DESIGN: A population-based case-control study of a sample of 65 997 participants from the Survey of Health, Ageing and Retirement in Europe study. Early parental death was operationalized as parental death at the age of ≤16 years. Main analyses were conducted using bivariate and multivariate logistic regression analyses. RESULTS: The odds ratio (OR) for dementia in individuals who experienced early parental death (father or mother) at the age of ≤16 years was 1.83 (95%CI 1.61-2.09) and 1.54 (95%CI 1.35-1.76) adjusted for age, gender and education. In the multivariate logistic regression analysis carried out with the whole sample, early parental death increased the risk of dementia (OR = 1.50, 95%CI 1.31-1.72), along with older age (OR = 5.92, 95%CI 4.86-7.17), neuroticism (OR = 2.94, 95%CI 2.61-3.31), low education level (OR = 1.84, 95%CI 1.64-2.05) and low income (OR = 1.49, 95%CI 1.34-1.67). DISCUSSION: Early parental death (≤16 years) was associated with an increased risk of dementia. We discuss the neurobiological markers associated with adverse childhood experiences (ACEs) and dementia as well as interventions to counteract the negative health effects on adults. J Am Geriatr Soc 68:-, 2020.

Antonovsky's sense of coherence and resistance resources reduce perception of burden in family carers of people with Alzheimer's disease.

Objectives: Taking care of people with dementia (PWD) has been associated with some degree of burden. The variability of the carer's burden can be partially explained by their personal characteristics. Antonovsky's model of health defined the resistance resources (RRs) as essential mechanisms to cope with stressors, and to shape the personal sense of coherence (SOC). This study identifies the RRs related with carer's SOC, and their implications in the perception of burden in family dementia carers.Methods: A sample of 308 participants from the 'SOC & DEM study' (154 carers and 154 PWD) was recruited from two memory clinics. Carer's personal characteristics of burden, SOC, self-efficacy, coping strategies, perceived social support, and depression were evaluated using standardized instruments. PWD's degree of dependence and behaviour and psychological symptoms of dementia (BPSD) were assessed too. A path analysis was used to test the relationship between caregiver burden and SOC including the personal RRs of the carers and clinical data of PWD.Results: The path model identified SOC as a major factor related to carer's burden perception (r = -.327). Self-efficacy (r = .285), two coping strategies, 'use instrumental support' (r = -.235) and 'behavioural disengagement' (r = -.219), and social support perceived (r = .304) were the main carer's personal characteristics directly related with SOC. Caring experience (r = -.281) was the main carer factor related with burden while dependence (r = .156) and BPSD (r = .157) were the dementia factors.Conclusion: The SOC has previously related with carer's burden. The results contributed to identify relevant and modifiable personal characteristics as RRs that could reduce this burden.

Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube.

INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.

Study of the strength of the evidence and the redundancy of the research on pharmacological treatment for Alzheimer's disease: a cumulative meta-analysis and trial sequential analysis.

PURPOSE: To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to determine the number of redundant post-authorisation trials. METHODS: A cumulative meta-analysis with a trial sequential analysis (TSA) was performed. Primary outcomes were cognitive function assessed with ADAS-cog or SIB scales, discontinuation due to adverse events (AE) and discontinuation for any reason. The redundancy of post-authorisation clinical trials was studied by determining the novel aspects of each study on patient, intervention, comparator and trial outcome characteristics. Two criteria of futile trial (lenient and strict) were used. RESULTS: A total of 63 randomised clinical trials (RCTs) (16,576 patients) were included. It was conclusive that neither ChEI nor memantine achieved clinically significant improvement in cognitive function. In relation to safety, there was sufficient evidence to conclude that donepezil caused a clinically relevant increase on dropouts due to AE whereas the evidence was inconclusive for the remaining interventions. Regarding acceptability, it was conclusive that no ChEI improved treatment discontinuation while it was uncertain for memantine. The proportion of redundant trials was 5.6% with the lenient criteria and 42.6% with the strict one. CONCLUSIONS: The evidence is conclusive that ChEI and memantine do not achieve clinically significant symptomatic improvement in AD while the acceptability of ChEI is unsatisfactory. Although evidence on the safety of pharmacological interventions for AD and acceptability of memantine is inconclusive, no further RCTs are needed as their efficacy is not clinically relevant. Redundant trials were identified but their number depends on the criteria of futility used.

Incidence and characteristics of uncommon dementia subtypes: Results from 10 years of clinical surveillance by the Registry of Dementia of Girona.

INTRODUCTION: Age- and sex-stratified incidence rates of uncommon dementia subtypes are imprecise and scarce. METHODS: We used data from 7357 newly diagnosed individuals aged between 30.6 and 101.0 years from the Registry of Dementia of Girona during 2007-2016 to determine the incidence rates of uncommon dementia subtypes stratified by sex and age groups and to describe their clinical characteristics. RESULTS: Uncommon dementia subtypes were classified according to their etiology. The incidence rate of uncommon dementia subtypes was 27.8 cases per 100,000 person-years for those aged 30 years and older, 3.7 cases per 100,000 person-years for people aged less than 65 years, and 110.9 per 100,000 person-years for those aged 65 years and older. Age, sex, dementia severity, and medical comorbidities were different depending on the dementia subtype. DISCUSSION: There are differences in the incidence rates and the demographic and clinical characteristics among uncommon dementia subtypes for age and sex groups.

Measuring anticholinergic exposure in patients with dementia: A comparative study of nine anticholinergic risk scales.

OBJECTIVE: To describe the prevalence and concordance of anticholinergic exposure according to 9 published scales, to quantify the relative weight of the drug subtypes included in each scale, and to identify clinical variables related to anticholinergic exposure. METHODS: Observational and cross-sectional study using 5323 cases of dementia diagnosed in the 7 hospitals of the public health care system of the Health Region of Girona (Spain) between 2007 and 2014 and registered by the Registry of Dementias of Girona (ReDeGi). We used the Pharmacy database that includes all the drugs prescribed by specialist and primary care physicians and dispensed in pharmacies. We calculated the anticholinergic exposure using the scoring rules of each scale. Age, gender, place of residence, dementia subtype, Clinical Dementia Rating score, Mini-Mental Status Examination score, and Blessed Dementia Rating Score at the moment of dementia diagnose were retrieved from the ReDeGi. RESULTS: Prevalence of the annual anticholinergic exposure ranged from 36.3% to 69.0% according to the different scales, the concordance among scales was poor to moderate, and the central nervous system drugs accounted the most for anticholinergic exposure. Being in a nursing home, having depressive symptoms, having a non-Alzheimer's dementia subtype, the number of drug treatments, and the severity of dementia were main determinants of anticholinergic exposure. CONCLUSIONS: There is a large difference in outcomes among the 9 anticholinergic risk scales. Clinicians and researchers should be aware of these differences when using these instruments in patients with dementia.

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

BACKGROUND: The risk-benefit relationship of memantine treatment for Alzheimer's disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates. METHODS: A systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials. RESULTS: Eighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE. CONCLUSIONS: Our study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship. PROSPERO REGISTRATION: CRD42014015696 .

Factor structure of depressive symptoms using the EURO-D scale in the over-50s in Europe. Findings from the SHARE project.

OBJECTIVES: The aims of this study are: to analyze the factor structure of the EURO-D depression scale; to explore the variables associated with depressive symptoms in the total sample and in the EURO-D factors; and to compare the presence of depressive symptoms and the factor distribution in 15 European countries. METHOD: 62,182 participants in Wave 5 (2013) of the Survey of Health, Aging and Retirement in Europe (SHARE) were included. INSTRUMENTS: The SHARE study and the EURO-D scale. Factor, bivariate and multilevel analyses were performed. RESULTS: Higher levels of depressive symptoms were associated with a poorer self-perception of physical health (η2 = 0.22) and economic difficulties (η2 = 0.07). Factor analysis of the EURO-D identified two factors: Suffering and Motivation. Higher levels of depressive symptoms were associated with female gender and younger age (≤60) in the Suffering factor, and with less activity and exercise, older age (≥71), widowhood and lower educational level in the Motivation factor. Poorer self-perception of physical health and economic difficulties were associated with higher depressive symptomatology in both factors. CONCLUSIONS: Poorer self-perception of physical health, female gender, economic difficulties, widowhood, lower levels of activity and exercise and lower educational level were associated with higher depressive symptomatology. In the countries of southern Europe, the Motivation factor predominated.

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.

Background: We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer's disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.

Kinship and cohabitation in relation to caregiver burden in the context of Alzheimer's disease: a 24-month longitudinal study.

OBJECTIVES: The aims of the study were to identify the clinical characteristics of three groups of caregivers: spouses, live-in adult-child or non-live-in adult-child, and their relation to the degree of perceived burden (Caregiver Burden Interview). METHODS: The sample comprised 275 Alzheimer's disease primary caregivers, with a follow-up of 24 months. Cognitive, functional and behavioural characteristics were evaluated in persons with dementia, whilst sociodemographic data, use of socio-medical resources, physical and mental health and self-perceived burden were assessed in caregivers. Generalized estimating equations were used for longitudinal data analysis. RESULTS: Spouse caregivers were 45.0% men, sole caregivers (>80%), used few external resources and had worse physical health. The number of female adult-child caregivers was higher (>75%). The live-in adult-child group, compared with the non-live-in adult-child group, was less likely to be married, had a lower level of education, was more commonly the sole caregiver and used fewer external resources. The greatest burden was observed in live-in adult-child caregivers, and the lowest in the non-live-in adult-child group, with no significant variation in the follow-up for both groups. Spouses had an intermediate level of perceived burden, which rose significantly during follow-up (p < 0.001). CONCLUSIONS: Kinship and cohabitation with the persons with dementia were associated with different scores and evolution of the burden, with an increase in the follow-up of the spouses, and with more or less burden, depending on cohabitation, in the adult-child groups. Interventions to reduce the level of burden on caregivers should consider these differences. Copyright © 2017 John Wiley & Sons, Ltd.

Quality of life in people aged 65+ in Europe: associated factors and models of social welfare-analysis of data from the SHARE project (Wave 5).

PURPOSE: To analyse the clinical, sociodemographic and socioeconomic factors that influence perceived quality of life (QoL) in a community sample of 33,241 people aged 65+ and to examine the relationship with models of social welfare in Europe. METHODS: This was a cross-sectional study of data from Wave 5 (2013) of the Survey of Health, Ageing and Retirement in Europe (SHARE). The instruments used in the present study were as follows: sociodemographic data, CASP-12 (QoL), EURO-D (depression), indicators of life expectancy and suicide (WHO), and economic indicators (World Bank). Statistical analysis included bivariate and multilevel analyses. RESULTS: In the multilevel analysis, greater satisfaction in life, less depression, sufficient income, better subjective health, physical activity, an absence of functional impairment, younger age and participation in activities were associated with better QoL in all countries. More education was only associated with higher QoL in Eastern European and Mediterranean countries, and only in the latter was caring for grandchildren also related to better QoL. Socioeconomic indicators were better and QoL scores higher (mean = 38.5 ± 5.8) in countries that had a social democratic (Nordic cluster) or corporatist model (Continental cluster) of social welfare, as compared to Eastern European and Mediterranean countries, which were characterized by poorer socioeconomic conditions, more limited social welfare provision and lower QoL scores (mean = 33.5 ± 6.4). CONCLUSIONS: Perceived quality-of-life scores are consistent with the sociodemographic and clinical characteristics of participants, as well as with the socioeconomic indicators and models of social welfare of the countries in which they live.

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain.

BACKGROUND: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. METHODS: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). RESULTS: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95%CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. CONCLUSIONS: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain.

Factor structure and concurrent construct validity of ICG among bereaved substance users.

BACKGROUND: It is important to understand the repercussions of Complicated Grief (CG) symptoms in addictions. There are no studies to date which have examined the psychometric properties of any test of bereavement among people with substance use disorder (SUD). Participants with SUD can have a different experience of bereavement from other people and therefore could respond differently to the usual instruments which assess CG symptomatology. METHOD: This study aims to establish the psychometric properties of the Spanish adaption of the Inventory of Complicated Grief (ICG) in a sample of 196 bereaved drug dependent patients. RESULTS: Results indicate that the internal consistency of the Spanish ICG was high (Cronbach’s alpha=0.922). The Spanish IDC shows good psychometric properties and it is a useful tool to discriminate adaptive reactions to symptomatology of complicated grief. Four factors were identified: discomfort, non-acceptance, loneliness-isolation and presence of deceased. Those factors showed a good internal reliability (minimum Cronbach’s alpha=0.78). CONCLUSIONS: The results of the current study confirm the multidimensionality of CG’s symptomatology construct.

Dependence scale for Alzheimer's disease: relationship with other clinical indicators and psychometric properties.

The objective of this cross-sectional and multicenter study was to evaluate the psychometric properties of the Spanish version of the Dependence Scale (DS) and to assess the relationship between dependence and clinical measures according to disease severity. Medical comorbidities, cognitive status and functional status, behavior, dependence, caregiver burden, and medical and social resources were assessed using standardized instruments. The sample consisted of 343 patients (32.1% mild, 36.7% moderate, and 31.2% severe), the mean age was 78.9 years (standard deviation=7.4), and 67.0% were women. Criterion and construct validity index of DS were appropriate. The DS standard error of measurement was ±1.23. The explained variance in DS ranged between 0.598 and 0.731, and the relative contribution of clinical measures depended on disease severity. Current findings confirm that the Spanish version of the DS has appropriate psychometric indices and suggest that clinical indicators have different contribution to dependence according to disease severity.