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The aim was to systematically review the effectiveness and safety of telemedicine combined with usual care (in-person visits) compared to usual care for the therapeutic management and follow-up assessment of neurological diseases.The electronic databases MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched (June 2021). Randomized controlled trials (RCTs) on patients of any age with neurological diseases were considered. Two reviewers screened and abstracted data in duplicate and independently and assessed risk of bias using the Cochrane risk-of-bias tool for randomized trials (RoB 2). When possible, pooled effect estimates were calculated.Of a total of 3018 records initially retrieved, 25 RCTs (n = 2335) were included: 11 (n = 804) on stroke, four (n = 520) on Parkinson's disease, three (n = 110) on multiple sclerosis, two (n = 320) on epilepsy, one (n = 63) on dementia, one (n = 23) on spina bifida, one (n = 40) on migraine, one (n = 22) on cerebral palsy and one (n = 433) on brain damage. Types of telemedicine assessed were online visits (11 studies), tele-rehabilitation (seven studies), telephone calls (three), smartphone apps (two) and online computer software (two). The evidence was quite limited except for stroke. Compared to usual care alone, telemedicine plus usual care was found to improve depressive symptoms, functional status, motor function, executive function, generic quality of life, healthcare utilization and healthy lifestyle in patients in post-stroke follow-up.Well-designed and executed RCTs are needed to confirm our findings on stroke and to have more scientific evidence available for the other neurological diseases.

In the Alzheimer Management by Albumin Replacement (AMBAR) study, mild-to-moderate Alzheimer's disease (AD) patients were treated with a plasma exchange (PE) program. Feasibility and safety of PE in this specific population are poorly understood and were analyzed in detail in this study.Qualified patients were treated with 6 weeks of weekly conventional therapeutic plasma exchange (TPE) with albumin replacement followed by monthly low-volume plasma exchange (LVPE) for 12 months. The patients were divided into four groups: placebo (sham PE treatment), low-albumin (20 g), low-albumin + intravenous immunoglobulin (IVIG) (10 g), and high-albumin (40 g) + IVIG (20 g). Adverse events (AEs) were recorded and analyzed for all PE treatment groups and PE modalities.PE procedure-related AEs were more common in the active treatment groups (16.9% out of 1283 TPE and 12.5% out of 2203 LVPE were associated with at least one AE, a similar rate than in other PE indications) than in the placebo group (0.7% out of 1223 sham PE). Percentage of procedures with at least one AEs was higher with central venous access compared to peripheral venous access in all three active treatment groups (20.1% vs 13.1%, respectively).The TPE and LVPE procedures used in the AMBAR study on mild-to-moderate AD population were as safe and feasible as in other therapeutic applications of PE or routine plasmapheresis.

The COVID-19 pandemic added a new stress source for caregivers. Many aspects influence the potential depressive or anxiety symptomatology in caregivers. This study explored the association among COVID-19 related stressors, insomnia, leisure, and caregivers' depression and anxiety. 101 family caregivers of people with dementia were asked about COVID-19 related stressors, insomnia, leisure, depression and anxiety symptoms. Four regression models with caregivers' depression and anxiety symptoms as dependent variables were tested. Four potential mediation models were investigated. Two of them had insomnia as the independent variable and leisure as a mediator, and the other two had leisure as the independent variable and insomnia as a mediator. Regression models accounted for 48% and 40.6% of the variance in depressive and anxiety symptoms, respectively. The four mediator models were statistically significant. Findings suggest two potential mechanisms affecting caregivers' distress during the pandemic. Insomnia and leisure significantly contributed to explain caregivers' anxiety and depressive symptoms, even after controlling for COVID-19 related stressors. Provision of resources to increase the chances of caregivers engaging in leisure activities, alongside a reduction of barriers potentially limiting good sleep, may contribute significantly to improving the depression and anxiety symptoms of family caregivers.

Introduction We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). Methods Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. Results The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). Discussion PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

Background: Over- and potentially inappropriate prescribing of psychotropic medications is a major public health concern among people with dementia. Objective: Describe the CHemical Restraints avOidance MEthodology (CHROME) criteria and evaluate its effects on psychotropic prescribing and quality of life (QoL). Methods: Observational, prospective, two-wave study conducted in two nursing homes. A multicomponent program to eliminate chemical restraints and attain quality prescription of psychotropic medications was implemented. CHROME’s diagnostic criteria comprise constellations of behavioral and psychological symptoms of dementia under six primary syndromic diagnoses. Since pharmacologic treatment is aimed at only one syndrome, polypharmacy is avoided. Psychotropic prescription, QoL, neuropsychiatric symptoms (NPS), and other clinical measurements were collected before and one year after the intervention. Results are presented for all residents (n = 171) and for completer subjects (n = 115). Results: Mean age (SD) of the residents was 87.8 (5.7), 78.9% were women, and 68.5% suffered advanced dementia. Psychotropic prescriptions decreased from 1.9 (1.1) to 0.9 (1.0) (p

Comorbid depression and anxiety is linked to worse outcomes such as increased impairment, distress, and morbidity, as well as worse treatment outcomes. Transdiagnostic variables such as cognitive fusion are considered potential factors for explaining comorbidity. The aim of this study was to analyze the differences between symptom profiles of caregivers (comorbid, depressive, anxiety, and subclinical) in terms of demographic and contextual factors, stress variables, and cognitive fusion. Individual interviews were conducted with 553 caregivers of a relative with dementia. Sociodemographic variables, stressors, cognitive fusion, and depressive and anxiety symptoms were assessed. Caregivers were grouped into four symptom profiles, comorbid (n = 303), depressed (n = 40) anxiety (n = 86), and subclinical (n = 124), based on their depressive and anxiety symptoms. The likelihood of presenting a comorbid profile relative to the subclinical profile was higher in female caregivers. In addition, higher frequency of disruptive behaviors of the care recipient was a risk factor for presenting a comorbid profile relative to the other three profiles, and higher scores in cognitive fusion were a risk factor of comorbidity relative to the other profiles (anxiety, depressive, and subclinical). The findings suggest that the likelihood of presenting comorbid symptomatology is higher for female caregivers and those reporting higher levels of cognitive fusion and higher frequency of disruptive behaviors. These characteristics may describe a vulnerable profile of dementia family caregivers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Behavioral and psychological symptoms of dementia (BPSD) are considered to cause ambivalent feelings in caregivers that may contribute to understanding their depressive symptoms. Transnational research is needed in order to increase our knowledge about the cross-cultural equivalence of theoretical models to understand caregivers' mental health. The aim of this study was to cross-culturally analyze the association between BPSD, ambivalent feelings and depressive symptoms in two samples of family caregivers of people with dementia from Spain and the UK.Participants in this study were 432 caregivers who completed measures of BPSD, ambivalent feelings and depressive symptoms. The association between the assessed variables was tested through path-analysis, with differences between countries tested through multigroup analysis.The results suggest that the influence of BPSD on caregivers' depressive symptoms is indirect, through ambivalent feelings. The observed associations were equivalent between countries and explained a significant percentage of the variance of depressive symptoms.The findings of this study provide, for the first time, evidence of equivalent cross-cultural paths analyzing the role of ambivalent feelings for understanding caregivers' depressive symptoms. The practical implications of these results are discussed.

Objectives: To analyze caregivers' perceived impact of the pandemic in their mental health and the well-being of the care-recipients.Methods: Caregivers (N = 88) were asked if they had COVID-19 and about their perceptions of change of care-recipients' health conditions as well as whether their own mental health, conflicts with care-recipients and other relatives, thoughts of giving up caregiving, and feelings of coping well with the situation.Results: A large percentage of caregivers perceived a worsening of care-recipients' symptoms and of their own negative emotions, an increase in the number of conflicts and thoughts of needing to give up caregiving. Having had COVID-19 and reporting higher levels of distress as well as giving up caregiving were related to perceived worsening in care-recipients well-being. Perceived increases were mainly reported by younger caregivers, those who perceived to have not coped well, and those reporting an increase in conflicts. Some caregivers perceived an increase in positive emotions.Conclusions: The pandemic has a negative impact on caregivers' perceptions about the course of their own emotions and care-recipients' well-being.Clinical implications: Interventions are needed to train caregivers in strategies to cope with the sources of stress caused by the pandemic and to promote social support.

Study objectives Family caregivers of people with dementia frequently report sleep problems that are linked to depressive and anxious symptoms. However, data are needed regarding the psychometric properties of specific measures of sleep problems in caregiving populations. The aim of this study is to analyse the psychometric properties of the Insomnia Severity Index (ISI; Morin, 1993) in a Spanish dementia caregiver sample. Methods 271 participants took part in face-to face interviews where, along with sociodemographic variables, caregivers' sleep problems, depressive and anxious symptoms were measured. The psychometric properties of the ISI were analysed through Confirmatory Factor Analysis (CFA) and analysis of the internal consistency and convergent and criterion validity. Results The Spanish version of the Insomnia Severity Index showed adequate indices of internal consistency (Cronbach's alpha = 0.78) in our sample of family caregivers of people with dementia. A one-factor structure provided a better fit to the data than two- and three-factor structures. The ISI was significantly associated with lower sleep quality, less average sleep time per day and lower self-perception of vitality, as well as with higher depressive and anxious symptoms. Differences in ISI scores were found between people with and without depressive and anxious symptoms. Statistically significant gender-based differences in sleep problems were also found, with female caregivers showing higher sleep problems. Conclusions The ISI is a reliable and valid instrument to assess the subjective severity of sleep problems in the family dementia caregiver population and may be a useful instrument in intervention and research settings. Additional evidence was also provided of the importance of considering sleep problems in the studied population.

Background: Comprehensive clinicopathological studies of neuropsychiatric symptoms (NPS) in dementia are lacking. Objective: To describe the pathological correlations of NPS in a sample of institutionalized people with dementia. Methods: We studied 59 people who were consecutively admitted to a nursing home and donated their brain. Correlations between pathological variables and NPS upon admission (n = 59) and at one-year follow-up assessment (n = 46) were explored and confirmed using bivariate and multivariate statistical methods. Results: Mean (SD) age at admission was 83.2 (6.4) years and mean (SD) age at demise was 85.4 (6.6); 73% of the subjects were female and 98% presented advanced dementia. The most frequent etiological diagnosis was Alzheimer’s disease (AD; 74.6% clinical diagnosis, 67.8% pathological diagnosis). The pathological diagnosis of AD was associated with aggression (β est 0.31), depression (β est 0.31), anxiety (β est 0.38), and irritability (β est 0.28). Tau stage correlated with aggressive symptoms (β est 0.32) and anxiety (βest 0.33). Coexistence of AD and Lewy body pathology was associated with depression (β est 0.32), while argyrophilic grains were associated with eating symptoms (β est 0.29). Predictive models were achieved for apathy, including cognitive performance, basal ganglia ischemic lesions, and sex as predictors (R2 0.38) and for sleep disorders, including pathological diagnosis of AD and age at demise (R2 0.18) (all p-values

Introduction This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer's disease (AD). Methods Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham). Results PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P

To analyze the association between diverse medical conditions and depressive symptoms in different profiles of dementia caregivers based on sex and kinship (wives, husbands, daughters, and sons).Individual interviews were conducted with 338 dementia family caregivers. Depressive symptoms were measured with the Spanish version of the Center for Epidemiologic Studies-Depression Scale. Medical conditions encompassed the following physical diseases: high cholesterol, osteoarthritis, hypertension, diabetes, cancer, and cardiovascular, brain, kidney, liver, and stomach diseases.Logistic regression analyses were carried out to identify determinants associated to thepresenceof depressive symptoms.High cholesterol was the most frequent disease among caregivers.Significant differences among groups were found in depressive symptoms: between wives (50.60%) and husbands (28.40%),(p = 0.033), and between daughters (57.00%) and husbands (p = 0.001). Half of the sonsreported thepresenceof depressive symptoms. In daughters, depressive symptomatology was significantly more likely whether they presented a worse reaction to disruptive behaviors, a poor assessment of global deterioration of care recipient, and less perceived health status. Furthermore, daughters were 1.94 times more likely to experience depressive symptoms if they presented medical conditions (p = 0.017).Daughter caregivers that have depressive and physical diseases may be an especially vulnerable subgroup of caregivers that may not be the ideal population to provide care. Access to high-quality, evidence-based therapies focused on improving caregivers' physical health could have a positiveeffecton thepresenceof depressive symptoms, particularly in the case of daughter caregivers.

Objectives:Caring for a relative with dementia is associated with adverse consequences for cardiovascular health. Cognitive and behavioral factors, such as high perceived activity restriction and low frequency of pleasant events have been found to be associated with higher levels of blood pressure, but the role these variables play in the stress and coping process remains understudied. The objective of this study is to analyze the associations between behavioral and psychological symptoms of dementia, activity restriction, frequency of pleasant events, and mean arterial pressure.Design:Face-to-face interviews and cross-sectional analyses.Setting:Social services, healthcare centers, and adult day services of Comunidad de Madrid, Spain.Participants:One hundred and two family caregivers of a spouse or parent with dementia.Measurements:Apart from various sociodemographic and health-related variables, behavioral and psychological symptoms of dementia, activity restriction, and frequency of leisure activities were assessed. In addition, measurement of blood pressure levels was conducted through an electronic sphygmomanometer.Results:The obtained model suggests that there is a significant indirect association between behavioral and psychological symptoms of dementia and mean arterial pressure through activity restriction and frequency of pleasant events.Conclusions:The findings of this study provide preliminary support for a potential indirect effect between behavioral and psychological symptoms of dementia and blood pressure, through the effects of behavioral and psychological symptoms of dementia on the caregivers’ levels of activity restriction and frequency of pleasant activities. Our manuscript provides additional support for the pleasant events and activity restriction model (Mausbach et al., 2011; Chattillion et al., 2013), by highlighting the importance of considering caregiving stressors as a source of caregivers’ activity restriction in the theoretical framework of the model.

Background: There is high prevalence of neuropsychiatric symptoms (NPS) among dementia patients. NPS are correlated with dementia progression, functional decline, early institutionalization, and death. There is scarce evidence on the progression of NPS in the latest stages of dementia. Objective: To describe the prevalence of NPS in mild-moderate to severe dementia and to reveal the progression of each NPS over time. Methods: We studied 317 patients (77.3% female, average age: 81.5 years) with a DSM-IV-TR diagnosis of dementia. This is a cross-sectional, and a prospective longitudinal study with 78-month follow-up. We assessed cognitive status (Mini-Mental State Examination and Severe Mini-Mental State Examination), dementia severity (Global Deterioration Scale and Clinical Dementia Rating), and psychopathological measures (Neuropsychiatric Inventory, APADEM-Nursing Home, Apathy Inventory, Cornell Scale for Depression in Dementia, and Cohen-Mansfield Agitation Inventory). Results: Overall prevalence of NPS was 94.6%, being apathy the most prevalent (66.7%) and the one whose severity increased the most with progression of dementia. Agitation/aggression, irritability, and sleeping and eating disorders also increased over time. Delusions and depressive symptoms decreased in severity with disease progression. In severe dementia, female displayed more depressive symptoms and eating disorders, while male displayed more agitation/aggression and sleep disturbances. Conclusion: NPS in dementia follow a heterogeneous course. Apathy is the most prevalent NPS and the one that worsens most significantly over time. The course of some NPS differs between sexes. Further research is required to understand the evolution of NPS at advanced stages of dementia.

Background:Chronic drug intake has been associated with negative and positive cognitive effects in elderly people, although subjacent conditions may be confounding factors.Aim:To study the effects on cognitive performance of commonly prescribed medications in a cohort of cognitively normal older adults.Methods:Medication intake was recorded during two years in 1087 individuals 70–85 years old, without neurological or psychiatric conditions. The influence of every drug, drug family and therapeutic group on six cognitive scores and on the conversion to mild cognitive impairment over two years was ascertained by cross-sectional and longitudinal analyses controlling for demographic and clinical variables.Results:Small effects of several drugs on information processing were found in cross-sectional analyses but only confirmed for a positive effect of vitamin D in case–control analyses. Longitudinal analyses showed no drug effects on the cognitive slopes. Several hypotensive drugs reduced, whereas bromazepam and glucose lowering drugs increased, the conversion rate to mild cognitive impairment with very small effects ( R2=0.3–1%).Conclusions:Cognitively healthy elderly individuals show minimal negative effects on information processing associated with chronic intake of some drugs probably related to the subjacent condition. Some drugs slightly affect the rate of conversion to mild cognitive impairment. Positive effects of vitamin D, chondroitin, atorvastatin and antihypertensive drugs, and negative effects of antidepressants and benzodiazepines, should be further explored in studies with longer follow-up.

Background: While most intervention studies conducted with dementia family caregivers have focused on depressive symptoms as the main outcome, no study has analyzed the effects of an intervention on comorbid clinical presentations of depressive and anxious symptomatology. Objective: The aim of this study was to examine the association between clinical depressive and anxious symptomatology at baseline and treatment responses of dementia family caregivers using samples from two randomized intervention trials with the same pre-post design. Methods: Specifically, the effects on depressive and anxious comorbidity of three intervention conditions (Cognitive Behavioral Therapy (CBT), Acceptance and Commitment Therapy (ACT), and a control group (CG)) were analyzed. Participants were 130 dementia family caregivers. In addition to sociodemographic variables, depressive and anxious symptomatology were measured. Results: Caregivers with clinical depressive and anxiety comorbid symptoms at baseline recovered less well from depressive symptoms after CBT (45.45%) and ACT (47.72%) interventions than caregivers with non-comorbidity (100% recovery in both treatments). No significant association between comorbidity and treatment responses on depression was found for the control group. Regarding anxiety, among participants with comorbidity at baseline, 36.36% of caregivers in CBT and 30.9 % in the ACT group recovered from anxiety symptoms after treatment, compared to 6.45% in the control group. Similar results were obtained regarding those caregivers who recovered both from clinical depressive and anxiety symptoms and showed comorbidity at baseline. Conclusion: Caregivers that show comorbid depressive and anxiety symptoms at baseline may benefit less from interventions than caregivers who do not show comorbidity.

Objective:Describe and validate the CHROME (CHemical Restraints avOidance MEthodology) criteria.Design:Observational prospective longitudinal study.Setting:Single nursing home in Las Palmas de Gran Canaria, Spain.Participants:288 residents; mean age: 81.6 (SD 10.6). 77.4% had dementia.Intervention:Multicomponent training and consultancy program to eliminate physical and chemical restraints and promote overall quality care. Clinicians were trained in stringent diagnostic criteria of neuropsychiatric syndromes and adequate psychotropic prescription.Measurements:Psychotropic prescription (primary study target), neuropsychiatric syndromes, physical restraints, falls, and emergency room visits were semi-annually collected from December 2015 to December 2017. Results are presented for all residents and for those who had dementia and participated in the five study waves (completer analysis, n=107).Results:For the study completers, atypical neuroleptic prescription dropped from 42.7% to 18.7%, long half-life benzodiazepines dropped from 25.2% to 6.5%, and hypnotic medications from 47.7% to 12.1% (ppConclusions:Implementing the CHROME criteria reduced the prescription of the most dangerous medications in institutionalized people with dementia. Two independent audits found no physical or chemical restraint and confirmed prescription quality of psychotropic drugs. Adequate diagnosis and independent audits appear to be the keys to help and motivate professionals to optimize and reduce the use of psychotropic medication. The CHROME criteria unify, in a single compendium, neuropsychiatric diagnostic criteria, prescription guidelines, independent audit methodology, and minimum legal standards. These criteria can be easily adapted to other countries.

Background: Alzheimer's disease (AD) and other forms of dementia are among the most common causes of disability in the elderly. Dementia is often accompanied by depression, but specific diagnostic criteria and treatment approaches are still lacking. This study aimed to gather expert opinions on dementia and depressed patient management to reduce heterogeneity in everyday practice.Methods: Prospective, multicenter, 2-round Modified Delphi survey with 53 questions regarding risk factors (11), signs and symptoms (7), diagnosis (8), and treatment (27) of depression in dementia, with a particular focus on AD. The questionnaire was completed by a panel of 37 expert physicians in neurodegenerative diseases (19 neurologists, 17 psychiatrists, and 1 geriatrician).Results: Consensus was achieved in 40 (75.5%) of the items: agreement in 33 (62.3%) and disagreement in 7 (13.2%) of them. Among the most relevant findings, depression in the elderly was considered an early sign (prodromal) and/or a dementia risk factor, so routine cognitive check-ups in depressed patients should be adopted, aided by clinical scales and information from relatives. Careful interpretation of neuropsychological assessment must be carried out in patients with depression as it can undermine cognitive outcomes. As agreed, depression in early AD is characterized by somatic symptoms and can be differentiated from apathy by the presence of sadness, depressive thoughts and early-morning awakening. In later-phases, symptoms of depression would include sleep-wake cycle reversal, aggressive behavior, and agitation. Regardless of the stage of dementia, depression would accelerate its course, whereas antidepressants would have the opposite effect. Those that improve cognitive function and/or have a dual or multimodal mode of action were preferred: Duloxetine, venlafaxine/desvenlafaxine, vortioxetine, tianeptine, and mirtazapine. Although antidepressants may be less effective than in cognitively healthy patients, neither dosage nor treatment duration should differ. Anti-dementia cholinesterase inhibitors may have a synergistic effect with antidepressants. Exercise and psychological interventions should not be applied alone before any pharmacological treatment, yet they do play a part in improving depressive symptoms in demented patients.Conclusions: This study sheds light on several unresolved clinical challenges regarding depression in dementia patients. Further studies and specific recommendations for this comorbid patient population are still needed.

Culture-related variables, such as personal values, have been suggested as important in stress processes, such as family caregiving of people with dementia. Personal values may be categorized into two dimensions: family and own personal values. Drawing upon the Sociocultural Stress and Coping model, the objective of this study is to analyze differences between caregivers depending on their values profiles.Participants were 333 family caregivers of a spouse or a parent with dementia. Caregivers chose their two most important values, apart from caregiving, from a list of eight family-related and non-family-related values (own values). Therefore, three values profiles were possible: Family-values profile (FVP: the two values are family related), Mixed-values profile (MVP: one family related value and one own value), and Own-values profile (OVP: two own values were selected). In addition to values, sociodemographic variables, commitment and satisfaction with caregiving value and with chosen values, ambivalent feelings, and anxiety and depression symptomatology were assessed. ANOVA analyses were conducted.The analyses suggest that caregivers in the FVP had lower levels of anxiety and ambivalent feelings and a higher commitment to and satisfaction with their chosen values than the other profiles. No differences were found for commitment and satisfaction with the caregiving value.Caregivers' value profiles seem to play an important role in the effects of stress over psychological health. Possible explanations of these effects about potential role conflicts and a higher commitment to values are discussed.

Background Predementia is a heuristic umbrella concept to classify older adults with cognitive impairment who do not suffer dementia. Many diagnostic entities have been proposed to address this concept, but most of them have not had widespread acceptance. Aims To review clinical definitions, epidemiologic data (prevalence, incidence) and rate of conversion to dementia of the main predementia constructs, with special interest in the two most frequently used: mild cognitive impairment (MCI) and minor neurocognitive disorder (miNCD). Methods We have selected in three databases (MEDLINE, Web of Science and Google scholar) the references from inception to 31 December 2019 of relevant reviews, population and community-based surveys, and clinical series with >500 participants and >3 years follow-up as the best source of evidence. Main results The history of predementia constructs shows that MCI is the most referred entity. It is widely recognized as a clinical syndrome harbinger of dementia of several etiologies, mainly MCI due to Alzheimer's disease. The operational definition of MCI has shortcomings: vagueness of its requirement of "preserved independence in functional abilities" and others. The recent miNCD construct presents analogous difficulties. Current data indicate that it is a stricter predementia condition, with lower prevalence than MCI, less sensitivity to cognitive decline and, possibly, higher conversion rate to dementia. Conclusions MCI is a widely employed research and clinical entity. Preliminary data indicate that the clinical use of miNCD instead of MCI requires more scientific evidence. Both approaches have common limitations that need to be addressed.

Background: Recent research pointed to executive dysfunction as a potential early predictor of the progression of mild cognitive impairment (MCI) to dementia in Alzheimer’s clinical syndrome (ACS). Such cognitive impairments account for functional impairments in instrumental activities of daily living (IADL). Objective: The present study analyzes the contributions of executive functions to predict MCI–dementia progression in ACS. Methods: We assessed 145 participants, 51 cognitively unimpaired and 94 MCI. The latter were divided using the traditional, memory-based MCI classification (single domain amnestic, multidomain amnestic, and non-amnestic). Eight tests assessing executive functions were administered at baseline and at 1-year follow-up, together with cognitive screening tools and IADL measures. MCI patients were reclassified based on the outcomes from a K-mean cluster analysis which identified three groups. A simple lineal regression model was used to examine whether the classification based on executive functioning could more accurately predict progression to dementia a year later. Results: Clusters based on executive function deficits explained a significant proportion of the variance linked to MCI–dementia conversion, even after controlling for the severity of MCI at baseline (F(1, 68) = 116.25, p = 0.000, R2 = 0.63). Classical memory-based MCI classification failed to predict such a conversion (F(1, 68) = 5.09, p = 0.955, R2 = 0.07). Switching, categories generation, and planning were the executive functions that best distinguished between MCI converters and stable. Conclusion: MCI with a dysexecutive phenotype significantly predicts conversion to dementia in ACS a year later. Switching abilities and verbal fluency (categories) must be evaluated in MCI patients to assess risk of future dementia.

Cross-sectional data show that caregivers’ ambivalent feelings are associated with psychological distress. The association of ambivalent feelings with caregivers’ cardiovascular risk has not been studied. For this purpose we analyzed preliminary data from the Spanish Longitudinal Caregiving Spanish Longitudinal Study (CUIDA-LONG). One-year follow-up data were available for 96 dementia family caregivers. The following variables were assessed: sociodemographics, body mass index (BMI), disruptive behaviors, ambivalence, depressive symptomatology and cardiovascular risk with the inflammatory biomarker C-reactive protein (CRP). A hierarchical regression model was tested. Sociodemographic variables and change over time in stressors, ambivalence and depression were entered as predictors of change in CRP. 27% of the variance in CRP was explained through the model. More time since being a caregiver, higher BMI and greater increase in ambivalence contributed significantly to an increase in CRP. Ambivalent feelings contribute significantly to the cardiovascular risk of those who care for a relative with dementia.

OBJECTIVES: Although research shows that nursing home staff experience significant levels of stress and burnout, studies analyzing the relationship of psychosocial variables on their feelings of anxiety are scarce. This study aims to analyze the relationship between psychosocial variables and levels of anxiety among staff. METHOD: Participants were 101 nursing home professionals. In addition to anxiety, socio-demographic variables, depersonalization, burden, relationship with families of the residents, and guilt about the care offered to the residents were assessed. A hierarchical regression analysis was carried out to analyze the contribution of the assessed variables to staff anxiety levels. RESULTS: The obtained model explained 57% of the variance in anxious symptomatology. Guilt about the care offered and poor quality of the relationship with residents’ family were associated with anxiety. Further, working at nursing homes where the staff report higher levels of anxiety symptoms, the presence of depersonalization and burden were also associated with anxiety. CONCLUSION: The findings suggest that in addition to work-related variables (burden and burnout), problems with family members and guilt about the care offered are relevant variables for understanding staff’s anxious symptomatology. CLINICAL IMPLICATIONS: Interventions that address issues of guilt about the quality of care, and problematic relationships with family members of residents, may have potential to reduce staff anxiety and promote their well-being.

Background:Country-specific data on resource use and costs associated with Alzheimer's disease (AD) help inform governments about the increasing need for medical and financial support as the disease increases in prevalence.Methods:GERAS II, a prospective observational study, assessed resource use, costs, and health-related quality of life (HRQoL) among patients with AD and their caregivers in Spain. Community-dwelling patients aged ≥55 years with probable AD, and their primary caregivers, were recruited by study investigators during routine clinical practice and assessed as having mild, moderate, or moderately severe/severe (MS/S) AD dementia based on patient Mini-Mental State Examination scores. Costs of AD were calculated by applying costs to resource-use data obtained in caregiver interviews using the Resource Utilization in Dementia instrument. Total societal costs included patients’ health and social care costs and caregiver informal care costs. Baseline results are presented.Results:Total mean monthly societal costs/patient (2013 values) were €1514 for mild (n = 116), €2082 for moderate (n = 118), and €2818 for MS/S AD dementia (n = 146) (p value Conclusions:Societal costs associated with AD in Spain were largely attributable to caregiver informal care costs and increased with increasing AD dementia severity.

Alzheimer's disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). We compared data from two studies on temporary binding which assessed people with MCI and controls using different memory loads (2 or 3 items). Selective binding impairments were found in MCI, but relative to controls, such selectivity was contingent upon memory load (i.e., present with 2 items). Further analysis with MCI people who tested positive to neuroimaging biomarkers (i.e., hippocampal atrophy) confirmed that this specific binding impairments are a feature of prodromal AD. The temporary binding task has been recently suggested by consensus papers as a potential screening tool for AD. The results presented here inform on task properties that can maximize the reliability of this new assessment tool for the detection of memory impairments in prodromal cases of AD.

Objective Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD). Methods The setting of the study was at the Alzheimer Center Reina Sofia Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted. Results Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 ± 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p

According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.

Background and Objectives: The existence of different patterns of functional impairment in older adults has scarcely been addressed. This research investigates major patterns of functional impairme...

Accurate blood-based biomarkers of Alzheimer's disease (AD) could constitute simple, inexpensive, and non-invasive tools for the early diagnosis and treatment of this devastating neurodegenerative disease. We sought to develop a robust AD biomarker panel by identifying alterations in plasma metabolites that persist throughout the continuum of AD pathophysiology. Using a multicenter, cross-sectional study design, we based our analysis on metabolites whose levels were altered both in AD patients and in patients with amnestic mild cognitive impairment (aMCI), the earliest identifiable stage of AD. UPLC coupled to mass spectrometry was used to independently compare the levels of 495 plasma metabolites in aMCI (n = 58) and AD (n = 100) patients with those of normal cognition controls (NC, n = 93). Metabolite alterations common to both aMCI and AD patients were used to generate a logistic regression model that accurately distinguished AD from NC patients. The final panel consisted of seven metabolites: three amino acids (glutamic acid, alanine, and aspartic acid), one non-esterified fatty acid (22:6n-3, DHA), one bile acid (deoxycholic acid), one phosphatidylethanolamine [PE(36:4)], and one sphingomyelin [SM(39:1)]. Detailed analysis ruled out the influence of potential confounding variables, including comorbidities and treatments, on each of the seven biomarkers. The final model accurately distinguished AD from NC patients (AUC, 0.918). Importantly, the model also distinguished aMCI from NC patients (AUC, 0.826), indicating its potential diagnostic utility in early disease stages. These findings describe a sensitive biomarker panel that may facilitate the specific detection of early-stage AD through the analysis of plasma samples.

Background: Little is known about the long-term acceptance and effects of cognitive and motor stimulation interventions (CMSI) in Alzheimer’s disease (AD). Objective: To evaluate a replicable CMSI program for mild cognitive impairment (MCI) and mild-to-moderate AD persons. Methods: Eighty-four non-institutionalized subjects with AD were randomized to receive either CMSI, administered by a single care provider, or standard support. Cognition, activities of daily living (ADL), mood, and study partner’s subjective burden were assessed by blinded raters. Data on institutionalization, psychiatric medications, and demise were collected by the study physicians. Random effects model and survival analyses were conducted, after 2 and 3 years of study. Results: Three-year assessments could be performed by the physician in 85% and by the blinded rater in 66% of subjects. Significant benefits were observed in basic ADL at the 2- and 3-year assessments, whereas instrumental ADL showed benefits only up to the second year of intervention (p < 0.05). Conclusion: Long-term cognitive-motor stimulation is well accepted and produces functional benefits in subjects with AD, with no extra subjective burden in the partner.

Apathy is one of the most frequent symptoms of dementia, still needing better measurement methods. The objective of this study was to validate a new scale for apathy in institutionalized persons with dementia (APADEM-NH).The scale includes 26 items distributed in three dimensions: Deficit of Thinking and Self-Generated behaviors (DT): 13 items, Emotional Blunting (EB): 7 items, and Cognitive Inertia (CI): 6 items. The sample included 100 institutionalized patients (90% female) with probable Alzheimer disease (AD) (57%), possible AD (13%), AD + cerebral vascular disease (17%), Lewy body dementia (11%), and Parkinson associated to dementia (2%), covering all stages of dementia severity according to the Global Deterioration Scale and Clinical Dementia Rating. Additional assessments were the Apathy Inventory, Neuropsychiatric Inventory, Cornell Scale for Depression, and the tested scale. Re-test and inter-rater reliability were carried out in 50 patients.All subscales lacked relevant floor and ceiling effects (15%). Internal consistency for each dimension was (Cronbach's α): DT = 0.88, EB = 0.83, CI = 0.88; item-total correlations were0.40; and item homogeneity 0.36-0.51. Test-retest reliability for the items was kW = 0.48-0.92; for the subscales, intraclass correlation coefficient (ICC) = 0.80-0.88; and for the total score, ICC = 0.90. Inter-rater reliability reached kW values of 0.84-1.00; subscales ICC, 0.97-0.99, and total score ICC, 0.99. Standard error of measurement for total score was 6.41 and internal validity ranged from rS = 0.69-0.80.APADEM-NH proved to be feasible, reliable, and valid for apathy assessment in institutionalized patients suffering mild to severe dementia, discerning well between apathy and depression.

Non-pharmacological therapies (NPT) are nonchemical, theoretically based, replicable interventions that produce relevant benefits for people with dementia and their caregivers. Three types of cognition-focused NPT are distinguished: cognitive stimulation (CS), which engages people with cognitive deterioration in a range of group activities and discussions aimed at general enhancement of cognitive and social functioning; cognitive training (CT), which focuses on particular cognitive functions; and cognitive rehabilitation (CR), which involves patients and family to achieve personally relevant goals. While CS is indicated in people with mild to moderate dementia for improvement in general cognition, CR faces the challenge to deliver cost-effective programmes.

Unawareness of deficit has been shown to affect the outcome of targeted cognitive intervention programmes applied to patients with Alzheimer' disease (AD), but the effects on multimodal therapeutic approaches have not yet been explored. This research investigated the efficacy of the Multi-Intervention Programme (MIP) approach on improving cognitive, functional, affective, and behavioural symptoms in people with mild AD. In addition, we examined whether the presence of unawareness influences the MIP outcomes. Sixty-one mild stage AD patients were randomly assigned to either an experimental group which carried out an MIP individually (48 sessions, 16 weeks duration), combining diverse cognitive tasks, training in daily life and recreational activities, or a waiting list group which did not receive any treatment for the same time period. The efficacy of MIP (vs. waiting list) was tested using various standardised neuropsychological, functional, and behavioural outcome measures. Planned analyses were carried out to determine the effect of unawareness versus awareness on such outcomes. The results showed that patients overall benefited from the MIP in terms of both cognitive and non-cognitive symptoms. AD patients with awareness of deficits showed positive effects on all outcome measures in comparison with the waiting list group, while AD patients with unawareness showed improvements in non-cognitive symptoms only. In conclusion, the presence of unawareness reduces the cognitive and functional effects of MIP in patients with mild AD.

Objective: A cross-sectional study was conducted to describe the prevalence, locations, and risk factors for brain microbleeds (BMBs) in neurodegenerative dementia. Methods: The database of the Alzheimer Center Reina Sofía Foundation was searched, BMBs were described, and the potential associations of BMBs were investigated using univariate statistics. Results: A total of 148 patients (age 81.6 [standard deviation 6.7], 79.1% female) were studied. Prevalence of BMBs was 44.6%. A group of patients with unusually high (ie, ≥4) number of BMBs were identified, which displayed higher number of vascular risk factors and vascular diseases. Brain microbleeds were also associated with ischemic lesions in the basal ganglia ( r = .39), clinical diagnosis of Alzheimer’s disease (AD) and cerebrovascular disease ( r = .33), cortical infarction ( r = .20), and antiaggregant or anticoagulant treatment duration ( r = .20). Conclusions: Brain microbleeds are associated with vascular burden and AD diagnosis in old patients with neurodegenerative dementia. More research is warranted regarding the mechanisms and potential clinical implications of these results.