[DemStepCare: Risk-stratified support for primary care-based dementia care - evaluation from general practitioner's view]. / DemStepCare: Risikostratifizierte Unterstützung der ambulanten Demenzversorgung ­ Bewertung aus hausärztlicher Perspektive.

OBJECTIVE: The innovation fund project DemStepCare aimed to optimize multi-professional care through case management, risk stratification, and crisis outpatient clinic. Here, the evaluation results from the perspective of the general practitioners are presented. METHODS: A quantitative survey was carried out at three time points regarding acceptance, benefit assessment and sensitivity to dementia of the general practitioners. In addition, qualitative interviews were conducted. RESULTS: Satisfaction with the overall project was high. Added value and relief factors were perceived and more effective and stable dementia care was achieved through collaboration with case management. Physicians reported increased subjective competence in diagnostics and disease management. CONCLUSIONS: The results confirm the benefit and effectiveness of DemStepCare from general practitioner's perspective.

Interhemispheric transfer time correlates with white matter integrity of the corpus callosum in healthy older adults.

The corpus callosum (CC) has been identified as an important structure in the context of cognitive aging (Fling et al., 2011). Interhemispheric transfer time (IHTT) is regularly used in order to estimate interhemispheric integration enabled by the CC (Marzi, 2010; Nowicka and Tacikowski, 2011). However, only little is known with regards to the relationship between IHTT and the structural properties of the CC with only few studies with specific samples and methods available (Whitford et al., 2011). Thus, the present study aimed at investigating this relationship applying an event-related potentials (ERP) based approach of estimating IHTT as well as diffusion weighted imaging (DWI) with fractional anisotropy (FA) as an indicator of white matter integrity (WMI) of the genu, corpus and splenium of the CC. 56 healthy older adults performed a Dimond Task while ERPs were recorded and underwent DWI scanning. IHTT derived from posterior electrode sites correlated significantly with FA of the splenium (r = -0.286*, p = .03) but not the corpus (r = -0.187, p = .08) or genu (r = -0.189, p = .18). The present results support the notion that IHTT is related to WMI of the posterior CC. It may be concluded that ERP based IHTT is a suitable indicator of CC structure and function, however, likely specific to the interhemispheric transfer of visual information. Future studies may wish to confirm these findings in a more divers sample further exploring the precise interrelation between IHTT and structural or functional properties of the CC.

Influence of loss- and restoration-oriented stressors on grief in times of COVID-19.

This study aimed to examine the influence of COVID-specific stressors on cross-sectional and longitudinal bereavement outcomes. According to the Dual Process Model of grief these stress-inducing factors can relate to the loss (loss-oriented stressors) or to manage everyday life (restoration-oriented stressors) and require coping in the grief process. A total of 491 participants (94.1% female; 43.92 years on average; 44.4% loss of a parent) were included at the first measurement time point (T0), of whom 99 individuals also participated in a follow-up assessment 6 months later (T1). Participants frequently reported loss-oriented (on average 7.30 out of 21 queried) and restoration-oriented stressors (on average 6.99 out of 19 queried). Cross-sectionally, higher acute grief intensity was associated with a higher number of loss-oriented stressors, poorer mental well-being, and sociodemographic variables. This effect disappeared longitudinally, with only acute grief intensity and poorer mental well-being at T0 predicting higher prolonged grief at T1. Common resilience factors did not buffer the effects of the pandemic on grief. Loss-oriented stressors seem to be especially relevant for understanding grief and might be a mediator of higher long-term grief. The findings suggest that COVID-specific strains need to be specifically taken into account in the support of bereaved individuals.

Public knowledge and attitudes about mental health in older age in Germany - Focus on dementia and late-life depression.

Older people with mental disorders represent a particularly vulnerable group in the health care system. Despite this, mental disorders in this group often remain undiagnosed or are not treated in accordance with guidelines, potentially due to a lack of knowledge or unfavorable attitudes regarding mental disorders in older individuals. Therefore, in an anonymous online survey of 1,284 participants (71.8% female, mean age 52.3 ± 18.0 years), we assessed knowledge and attitudes regarding mental health in old age in general and regarding dementia and late-life depression in particular. Regression analyses were conducted to determine predictors of higher knowledge and more favorable attitudes based on sociodemographic data. On average, participants answered 11 ± 2 out of 15 of the knowledge questions correctly. Items on the prevention of dementia, late-life depression symptoms, and associated suicide risk were most likely to be answered incorrectly. Participants showed less favorable attitudes towards people living with dementia than towards people with late-life depression, and higher knowledge scores were associated with more favorable attitudes. Our findings highlight a clear need for psychoeducation in the field of dementia and late-life depression, with a special emphasis on prevention-related knowledge. Fostering knowledge in this area is highly relevant, as it might positively influence attitudes towards older people with mental disorders, in turn facilitating health care and health-promoting behavior among older people.

The relationship between interhemispheric transfer time and physical activity as well as cardiorespiratory fitness in healthy older adults.

The structural and functional degradation of the corpus callosum (CC) has been shown to play an important role in the context of cognitive aging (Reuter-Lorenz and Stanczak, 2000). This is also reflected by findings of elongated interhemispheric transfer time (IHTT) in older adults (Riedel et al., 2022). At the same time, a protective effect of physical activity (PA) and cardiorespiratory fitness (CRF) on brain health including the CC is widely accepted (Hillman et al., 2008; Loprinzi et al., 2020). Based on this idea, the present study investigated the relationship between IHTT and PA/CRF in 107 healthy older adults (m: 64, f: 43) aged 67.69 ± 5.18. IHTT was calculated detecting event-related potentials (ERPs) using an established Dimond-Task. PA was evaluated using accelerometry resulting in estimates of overall bodily motion and time spent at higher intensity PA. CRF was estimated using graded exercise testing, approximating running speed at 4 mmol/l blood lactate concentration. The results showed a negative correlation between IHTTright→left and PA overall as well as in the male subgroup and between IHTTleft→right and CRF in women. This indicates a potential relationship between IHTT and PA/CRF. While the present investigation is only the first to hint at such a relationship taking into account the differential effects with regards to sex, mode of PA/CRF and IHTT direction, it is in line with previous findings and theoretical suggestions linking brain health to PA/CRF in the context of aging. Further research is needed in order to increase our understanding of the underlying mechanisms and of the influence of sex, PA intensity, degree of CRF and significance of IHTT direction.

Apathy in patients with Alzheimer's disease is a cost-driving factor.

BACKGROUND: Apathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers. METHODS: Included were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment. The Resource Utilization in Dementia (RUD) instrument assessed costs over a 1-month period prior to baseline. Cost predictors were determined via a least absolute shrinkage and selection operator (LASSO). RESULTS: On average, total monthly costs were €3070, of which €2711 accounted for caregivers' and €359 for patients' costs. An increase of one point in the Apathy Evaluation Scale resulted in a 4.1% increase in total costs. DISCUSSION: Apathy is a significant cost driving factor for total costs in mild to moderate DAT. Effective treatment of apathy might be associated with reduced overall costs in DAT.

Psychobiological Evaluation of Day Clinic Treatment for People Living With Dementia - Feasibility and Pilot Analyses.

Background: Hospitalization is often stressful and burdensome for people living with dementia (PwD) and their informal caregivers (ICs). Day clinic treatment may provide a suitable alternative, but is often precluded by a diagnosis of dementia. Furthermore, it is often caregiver-based ratings that measure treatment success as the validity of self-reports in PwD is critically discussed. We therefore set out to examine the feasibility of psychobiological stress measures in PwD and ICs and to evaluate treatment trajectories considering both the day clinic context and the daily life of the dyads. Method: A total of 40 dyads of PwD (mean age: 78.15 ± 6.80) and their ICs (mean age: 63.85 ± 13.09) completed paper-and-pencil questionnaires (covering stress, depressive symptoms, and caregiver burden among others) in addition to the measurement of hair cortisol concentrations (HCC) at admission, discharge, and follow-up 6 months after day clinic treatment. As part of an ambulatory assessment, for 2 days at the beginning and 2 days at the end of the day clinic treatment, PwD and ICs collected six saliva samples per day for the analysis of salivary cortisol (sCort) and alpha-amylase (sAA). Results: Paper-and-pencil questionnaires and HCC assessments were more feasible than the ambulatory assessment. We found discrepancies between subjective and physiological markers of stress in PwD. Whereas HCC decreased over time, self-reported stress increased. Child-parent dyads reported decreases in neuropsychiatric symptoms, associated burden, and self-reported stress from admission to follow-up. In daily life, both PwD and ICs showed characteristic diurnal profiles of sAA and sCort, however, we found no differences in summary indicators of salivary stress markers over time. Discussion: The psychobiological evaluation was feasible and added informative value, underlining the potential of physiological stress markers to complement self-reports on stress in PwD and to objectively evaluate treatment trajectories. In this sample, HCC was more feasible and acceptable as biological marker of stress compared to saliva samples. Concerning treatment trajectories, differential effects on the dyads were found, with child-parent dyads benefiting more from day clinic treatment compared to spousal dyads.

Psychobiological Monitoring of a Home-Based Dyadic Intervention for People Living with Dementia and Their Caregivers: Added Value to Evaluate Treatment Success and Understand Underlying Mechanisms.

BACKGROUND: Research concerning people living with dementia (PwD) and their informal caregivers (ICs) has recently begun to focus on dyadic aspects of psychosocial interventions. OBJECTIVE: We adapted a dyadic psychosocial intervention and examined its effects on psychobiological stress in daily life. METHODS: Twenty-four PwD-caregiver dyads were visited seven times at home by specialized nursing staff. Momentary subjective stress, salivary cortisol (sCort), and salivary alpha-amylase (sAA) were measured in PwD and ICs before and after each home visit as well as six times per day at two days each at the beginning and end of the intervention as part of an ambulatory assessment. Hair cortisol concentrations (HCC) were measured twice. RESULTS: After each home visit session, ICs reported lower subjective stress. sCort was lower in both ICs and PwD, whereas sAA did not change. In daily life, area under the curve (AUCg) concerning sCort secretion indicated that PwD had lower sCort daily output at the end of the intervention, and AUCg concerning subjective stress indicated that both PwD and ICs reported lower subjective stress than at the beginning of the intervention. AUCg concerning sAA did not change over time in either group. HCC did not vary over time but increased with disease severity. CONCLUSION: The psychosocial intervention reduced psychobiological stress but affected psychobiological stress measures differently in PwD and ICs. In particular, the discrepancy between subjective and physiological markers of stress in PwD emphasizes the added value to evaluate treatment success and understand underlying mechanisms as a complement to self-reports.

Lifetime musical training and cognitive performance in a memory clinic population: A cross-sectional study.

BACKGROUND: Music training has been found to be beneficial for young and healthy participants but the associations between musical training and the cognitive functioning of elderly participants have not been reported consistently. We examined whether lifetime musical training is associated with neuropsychological performance in a memory clinic population of older patients. METHODS: A total of 478 patients (54.2% female, mean age 73.70 ± 6.22, mean Mini Mental State Examination score 25 ± 3) were included in the cross-sectional analyses. All patients were referred to the memory clinic due to cognitive impairments. During the course of diagnosis, all patients underwent neuropsychological tests using the CERAD neuropsychological assessment battery. Patients provided information on whether they ever learned to play an instrument for at least five years in their life. RESULTS: Neuropsychological test results differed based on musical training (p = .042). Overall, there were no differences in any domains of cognitive functioning, other than that patients with musical training performed worse on word list memory (p = .008). However, this relationship varied based on the extent of cognitive impairments. Patients who were cognitively unimpaired (Mini Mental State Examination score 27-30) and had musical training showed better word list learning, whereas patients with cognitive impairments (Mini Mental State Examination score < 27) and musical training performed worse in word list learning (p = .042) and word list recall (p = .045). DISCUSSION: Overall, there was little evidence of associations between specific neuropsychological test results and musical training. Only in cognitively unimpaired patients was there evidence that musical training had beneficial associations. In patients with cognitive impairment, there were suggestions of negative associations with verbal memory. Future research should longitudinally investigate the beneficial effects of musical training in people with and without cognitive impairments.

The impact of aging on interhemispheric transfer time and respective sex differences.

Age-related cognitive decline has been attributed to degeneration of the corpus callosum (CC), which allows for interhemispheric integration and information processing [22,69]. Along with decreased structural integrity, altered functional properties of the CC may cause impaired cognitive performance in older adults, yet this aspect of age-related decline remains insufficiently researched [59]. In this context, potential sex-related differences have been proposed [31,58]. A promising parameter, which has been suggested to estimate functional properties of the CC is the interhemispheric transfer time (IHTT), which is ideally obtained from event-related potentials (ERP) evoked by lateralized stimuli [45]. To examine the possible functional consequences of aging with regards to the CC, the present study investigated the IHTT of 107 older (67.69 ±â€¯5.18y) as well as of 23 younger participants (25.09 ±â€¯2.59y). IHTT was obtained using an established letter matching task and targeting early N170 ERP components at posterior electrode sites. The results revealed significantly elongated IHTT in older compared to younger participants, but no significant sex differences. Furthermore, there was a significant positive correlation between IHTT and age, predominantly driven by the female participants. The present findings add support to the notion, that IHTT is subject to age-related elongation reflecting impaired interhemispheric transmission. Age-related decline in women appears to occur at a different age range compared to men.

Introduction and Psychometric Validation of the Resilience and Strain Questionnaire (ResQ-Care)- A Scale on the Ratio of Informal Caregivers' Resilience and Stress Factors.

Background: Informal caregivers are a particularly vulnerable population at risk for adverse health outcomes. Likewise, there are many scales available assessing individual caregiver burden and stress. Recently, resilience in caregivers gained increasing interest and scales started to assess resilience factors as well. Drawing on a homeostatic model, we developed a scale assessing both caregivers' stress and resilience factors. We propose four scales, two covering stress and two covering resilience factors, in addition to a sociodemographic basic scale. Based on the stress:resilience ratio, the individual risk of adverse health outcomes and suggestions for interventions can be derived. Methods: A total of 291 informal caregivers filled in the ResQ-Care as part of a survey study conducted during the second wave of the COVID-19 pandemic in Germany. Exploratory factor analysis was performed. Validity analyses were examined by correlations with the Brief Resilience Scale (BRS), the Perceived Stress Scale (PSS-4) and the Geriatric Depression Scale (GDS-15). Results: The data fitted our proposed four-factor solution well, explaining 43.3% of the variance. Reliability of each scale was at least acceptable with Cronbach's α ≥0.67 and MacDonald's ω ≥0.68 for all scales. The two strain scales weighed more than the resilience scales and explained 65.6% of the variance. Convergent and discriminant validity was confirmed for the BRS and PSS-4, whereas the GDS-15 correlation pattern was counterintuitive. Conclusion: The factor structure of the ResQ-Care scale was confirmed, with good indications of reliability and validity. Inconsistent correlations of the scales with the GDS-15 might be due to a reduced validity of GDS-15 assessment during the COVID-19 lockdown.

Primary dementia care based on the individual needs of the patient: study protocol of the cluster randomized controlled trial, DemStepCare.

BACKGROUND: Most people with dementia (PwD) are cared for at home, with general practitioners (GPs) playing a key part in the treatment. However, primary dementia care suffers from a number of shortcomings: Often, diagnoses are made too late and therapies by GPs do not follow the guidelines. In cases of acute crises, PwD are too often admitted to hospital with adverse effects on the further course of the disease. The aim of this study is to implement and evaluate a new GP-based, complex dementia care model, DemStepCare. DemStepCare aims to ensure demand-oriented, stepped care for PwD and their caregivers. METHODS/DESIGN: In a cluster randomized controlled trial, the care of PwD receiving a complex intervention, where the GP is supported by a multi-professional team, is compared to (slightly expanded) usual care. GPs are clustered by GP practice, with 120 GP practices participating in total. GP practices are randomized to an intervention or a control group. 800 PwD are to be included per group. Recruitment takes place in Rhineland-Palatinate, Germany. In addition, a second control group with at least 800 PwD will be formed using aggregated routine data from German health insurance companies. The intervention comprises the training of GPs, case management including repeated risk assessment of the patients' care situation, the demand-oriented service of an outpatient clinic, an electronic case record, external medication analyses and a link to regional support services. The primary aims of the intervention are to positively influence the quality of life for PwD, to reduce the caregivers' burden, and to reduce the days spent in hospital. Secondary endpoints address medication adequacy and GPs' attitudes and sensitivity towards dementia, among others. DISCUSSION: The GP-based dementia care model DemStepCare is intended to combine a number of promising interventions to provide a complex, stepped intervention that follows the individual needs of PwD and their caregivers. Its effectiveness and feasibility will be assessed in a formative and a summative evaluation. TRIAL REGISTRATION: German Register of Clinical Trials (Deutsches Register Klinischer Studien, DRKS), DRKS00023560 . Registered 13 November 2020 - Retrospectively registered. HTML&TRIAL_ID=DRKS00023560.

Dorsolateral Prefrontal Functional Connectivity Predicts Working Memory Training Gains.

Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training. Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19). Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task. Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

Structural Network Efficiency Predicts Resilience to Cognitive Decline in Elderly at Risk for Alzheimer's Disease.

Introduction: Functional imaging studies have demonstrated the recruitment of additional neural resources as a possible mechanism to compensate for age and Alzheimer's disease (AD)-related cerebral pathology, the efficacy of which is potentially modulated by underlying structural network connectivity. Additionally, structural network efficiency (SNE) is associated with intelligence across the lifespan, which is a known factor for resilience to cognitive decline. We hypothesized that SNE may be a surrogate of the physiological basis of resilience to cognitive decline in elderly persons without dementia and with age- and AD-related cerebral pathology.Methods: We included 85 cognitively normal elderly subjects or mild cognitive impairment (MCI) patients submitted to baseline diffusion imaging, liquor specimens, amyloid-PET and longitudinal cognitive assessments. SNE was calculated from baseline MRI scans using fiber tractography and graph theory. Mixed linear effects models were estimated to investigate the association of higher resilience to cognitive decline with higher SNE and the modulation of this association by increased cerebral amyloid, liquor tau or WMHV. Results: For the majority of cognitive outcome measures, higher SNE was associated with higher resilience to cognitive decline (p-values: 0.011-0.039). Additionally, subjects with higher SNE showed more resilience to cognitive decline at higher cerebral amyloid burden (p-values: <0.001-0.036) and lower tau levels (p-values: 0.002-0.015).Conclusion: These results suggest that SNE to some extent may quantify the physiological basis of resilience to cognitive decline most effective at the earliest stages of AD, namely at increased amyloid burden and before increased tauopathy.

Psychobiological mechanisms underlying the health-beneficial effects of music in people living with dementia: A systematic review of the literature.

BACKGROUND: Music has been used as agent in medicine for decades. The applications of music in health span from music therapy to music listening interventions to mere music listening. Music may reduce stress and improve health in people living with dementia (PwD), but the exact underpinnings of these effects are unclear. It is proposed that beneficial effects of music are mediated by a reduction in psychobiological stress. Therefore, the present review aims to shed light on the potential psychobiological mechanisms underlying the health-beneficial effects of music in PwD. METHODS: We searched for studies investigating health-beneficial effects of music in PwD by means of psychobiological stress measures using the PubMed, PsycINFO and Web of Science databases and by hand-searching. RESULTS: The inclusion criteria were met by 12 studies. Seven of the included studies investigated effects of music therapy on the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis or the immune system in patients with mild to moderate dementia. Results showed decreased ANS activity as measured by heart rate variability but no effect on alpha-amylase. Effects on blood pressure were mixed. Concerning the secretion of cortisol, one study found decreased HPA axis activity whereas two studies found no significant effects. No effects were found on salivary immunoglobin A. Three studies investigated the effects of music listening interventions in patients with severe dementia by means of predominantly ANS parameters with evidence indicating increased parasympathetic activation after music listening. Two studies investigated the effects of mere music listening on skin conductance using experimental designs. One study found increases in arousal due to music listening, whereas the other study found no effect. DISCUSSION AND CONCLUSION: These very preliminary results indicate effects of music on central stress pathways in PwD, but also highlight the need for further research focussing on a comprehensive assessment of autonomic, endocrine and immunological parameters in response to music. Furthermore, future studies should directly compare music therapy to music listening interventions and mere music listening in samples of PwD of varying disease severity and varying care settings.

The Impact of Age on the Association Between Physical Activity and White Matter Integrity in Cognitively Healthy Older Adults.

Cognition emerges from coordinated processing among distributed cortical brain regions, enabled through interconnected white matter networks. Cortical disconnection caused by age-related decline in white matter integrity (WMI) is likely to contribute to age-related cognitive decline. Physical activity (PA) has been suggested to have beneficial effects on white matter structure. However, its potential to counteract age-related decline in WMI is not yet well established. The present explorative study analyzed if PA was associated with WMI in cognitively healthy older adults and if this association was modulated by age. Forty-four cognitively healthy older individuals (aged 60-88 years) with diffusion-tensor imaging (DTI) and PA measurements were included from the AgeGain study. Voxelwise analysis using Tract-Based Spatial Statistics (TBSS) demonstrated that PA was associated with WMI in older adults. However, results emphasized that this association was restricted to high age. The association between PA and WMI was found in widespread white matter regions suggesting a global rather than a regional effect. Supplementary analyses demonstrated an association between the integrity of these regions and the performance in memory [verbal learning and memory test (VLMT)] and executive functioning (Tower of London).Results of the present explorative study support the assumption that PA is associated with WMI in older adults. However, results emphasize that this association is restricted to high age. Since cognitive decline in the elderly is typically most pronounced in later stages of aging, PA qualifies as a promising tool to foster resilience against age-related cognitive decline, via the preservation of the integrity of the brains WM.

Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed. Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Design, Setting, and Participants: This 12-week, multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in a psychiatric and neurological outpatient setting between July 2010 and July 2014 in Germany. Patients with mild-to-moderate dementia of Alzheimer type and clinically relevant apathy were included. Patients with additional clinically relevant depressed mood were excluded. Data analyses were performed between August 2018 and August 2019. Interventions: Patients received either bupropion or placebo (150 mg for 4 weeks plus 300 mg for 8 weeks). In case of intolerability of 300 mg, patients continued to receive 150 mg throughout the study. Main Outcomes and Measures: Change on the Apathy Evaluation Scale-Clinician Version (AES-C) (score range, 18-72 points) between baseline and week 12 was the primary outcome parameter. Secondary outcome parameters included measures of neuropsychiatric symptoms, cognition, activities of daily living, and quality of life. Outcome measures were assessed at baseline and at 4, 8, and 12 weeks. Results: A total of 108 patients (mean [SD] age, 74.8 [5.9] years; 67 men [62%]) were included in the intention-to-treat analysis, with 54 randomized to receive bupropion and 54 randomized to receive placebo. The baseline AES-C score was comparable between the bupropion group and the placebo group (mean [SD], 52.2 [8.7] vs 50.4 [8.2]). After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11). Results on secondary outcomes showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms (mean change, 5.52; 95% CI, 2.00 to 9.04; P = .003) and health-related quality of life (uncorrected for multiple comparisons; mean change, -1.66; 95% CI, -3.01 to -0.31; P = .02) with greater improvement in the placebo group. No statistically significant changes between groups were found for activities of daily living (mean change, -2.92; 95% CI, -5.89 to 0.06; P = .05) and cognition (mean change, -0.27; 95% CI, -3.26 to 2.73; P = .86). The numbers of adverse events (bupropion group, 39 patients [72.2%]; placebo group, 33 patients [61.1%]) and serious adverse events (bupropion group, 5 patients [9.3%]; placebo group, 2 patients [3.7%]) were comparable between groups. Conclusions and Relevance: Although it is safe, bupropion was not superior to placebo for the treatment of apathy in patients with dementia of Alzheimer type in the absence of clinically relevant depressed mood. Trial Registration: EU Clinical Trials Register Identifier: 2007-005352-17.

Apolipoprotein A1 in Cerebrospinal Fluid Is Insufficient to Distinguish Alzheimer's Disease from Other Dementias in a Naturalistic, Clinical Setting.

Apolipoprotein A1 (ApoA1) is the major protein component of the high-density lipoprotein and involved in cholesterol transport. Disruption of cholesterol homeostasis has been identified as a contributing factor for Alzheimer's disease (AD). Moreover, polymorphisms of ApoA1 have been associated with higher risk of disease onset and cognitive decline. Therefore, ApoA1 has been suggested as a biomarker in AD. Here, we tested a small cohort of AD and non-AD dementia patients and measured levels of ApoA1 in cerebrospinal fluid. Our results indicate that ApoA1 might not be applicable to distinguish AD from other forms of dementia.

The Synthetic Retinoid Acitretin Increases IL-6 in the Central Nervous System of Alzheimer Disease Model Mice and Human Patients.

These days, the important role of retinoids in adult brain functionality and homeostasis is well accepted and has been proven by genomic as well as non-genomic mechanisms. In the healthy brain, numerous biological processes, e.g., cell proliferation, neurogenesis, dendritic spine formation as well as modulation of the immune system, have been attributed to retinoid signaling. This, together with the finding that retinoid metabolism is impaired in Alzheimer's disease (AD), led to preclinical and early clinical testing of natural and synthetic retinoids as innovative pharmaceuticals with multifactorial properties. Acitretin, an aromatic retinoid, was found to exert an anti-amyloidogenic effect in mouse models for AD as well as in human patients by stimulating the alpha-secretase ADAM10. The lipophilic drug was already demonstrated to easily pass the blood brain barrier after i.p. administration and evoked increased nest building capability in the 5xFAD mouse model. Additionally, we analyzed the immune-modulatory capacity of acitretin via a multiplex array in the 5xFAD mouse model and evaluated some of our findings in human CSF derived from a pilot study using acitretin. Although several serum analytes did not display changes, Interleukin-6 (IL-6) was found to be significantly increased in both-mouse and human neural material. This demonstrates that acitretin exerts an immune stimulatory effect-besides the alpha-secretase induction-which could impact the alleviation of learning and memory disabilities observed in the mouse model.