Cholinergic modulation of motor sequence learning.

The cholinergic system plays a key role in motor function, but whether pharmacological modulation of cholinergic activity affects motor sequence learning is unknown. The acetylcholine receptor antagonist biperiden, an established treatment in movement disorders, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double-blind placebo-controlled crossover design, we tested 30 healthy young participants and showed that biperiden impairs the ability to learn sequential finger movements, accompanied by widespread oscillatory broadband power changes (4-25 Hz) in the motor sequence learning network after receiving biperiden, with greater power in the theta, alpha and beta bands over ipsilateral motor and bilateral parietal-occipital areas. The reduced early theta power during a repeated compared with random sequence, likely reflecting disengagement of top-down attention to sensory processes, was disrupted by biperiden. Alpha synchronization during repeated sequences reflects sensory gating and lower visuospatial attention requirements compared with visuomotor responses to random sequences. After biperiden, alpha synchronization was greater, potentially reflecting excessive visuospatial attention reduction, affecting visuomotor responding required to enable sequence learning. Beta oscillations facilitate sequence learning by integrating visual and somatosensory inputs, stabilizing repeated sequences and promoting prediction of the next stimulus. The beta synchronization after biperiden fits with a disruption of the selective visuospatial attention enhancement associated with initial sequence learning. These findings highlight the role of cholinergic processes in motor sequence learning.

Parietal cortical alpha/beta suppression during prospective memory retrieval.

Prospective memory (PM) impairment is among the most frequent memory complaints, yet little is known about the underlying neural mechanisms. PM for a planned intention may be achieved through strategic monitoring of the environment for cues, involving ongoing attentional processes, or through spontaneous retrieval. We hypothesized that parietal spectral power modulation accompanies prospectively encoded intention retrieval, irrespective of PM retrieval approach. A cognitively engaging arithmetic-based ongoing task (OGT) was employed to encourage spontaneous retrieval, with a focal, internally generated PM cue to eliminate OGT/PM trial differentiation based on perceptual or conceptual PM cue features. Two PM repetition frequencies were used to vary the extent of strategic monitoring. We observed a transient parietal alpha/beta spectral power reduction directly preceding the response, which was distinguishable on a single trial basis, as revealed by an OGT/PM trial classification rate exceeding 70% using linear discriminant analysis. The alpha/beta idling rhythm reflects cortical inhibition. A disengagement of task-relevant neural assemblies from this rhythm, reflected in alpha/beta power reduction, is deemed to increase information content, facilitate information integration, and enable engagement of neural assemblies in task-related cortical networks. The observed power reduction is consistent with the Dual Pathways model, where PM strategies converge at the PM retrieval stage.

Relative contributions of the face and body to social judgements: emotion, threat and status.

Do the nonverbal signals used to make social judgements differ depending on the type of judgement being made and what other nonverbal signals are visible? Experiment 1 investigated how nonverbal signals across three channels (face: angry/fearful, posture: expanded/contracted, lean: forward/backward), when viewed together, were used for judgements of emotion, threat, and status. Experiment 2 replicated Experiment 1 and explored how use of the body channels differed in making social judgements when the face channel was obscured. Both experiments found facial anger linked to high anger, threat, and status ratings; facial fear was linked to low ratings. Expanded body posture increased threat and status judgements, while backward lean decreased anger and threat. With the face channel blocked (Experiment 2B), the influence of body posture increased across emotion, threat, and status judgements, while body lean was more consistent. Findings demonstrate that despite the face's importance across types of social judgements, the body channels differentially contribute to judgements of emotion, threat and status. Further, they are differentially affected by the absence of facial information. How much face and body-related channels are used in social judgements is moderated by the type of judgement being made and the availability of other (particularly facial) channel information.

Suppression of Motor Sequence Learning and Execution Through Anodal Cerebellar Transcranial Electrical Stimulation.

Cerebellum (CB) and primary motor cortex (M1) have been associated with motor learning, with different putative roles. Modulation of task performance through application of transcranial direct current stimulation (TDCS) to brain structures provides causal evidence for their engagement in the task. Studies evaluating and comparing TDCS to these structures have provided conflicting results, however, likely due to varying paradigms and stimulation parameters. Here we applied TDCS to CB and M1 within the same experimental design, to enable direct comparison of their roles in motor sequence learning. We examined the effects of anodal TDCS during motor sequence learning in 60 healthy participants, randomly allocated to CB-TDCS, M1-TDCS, or Sham stimulation groups during a serial reaction time task. Key to the design was an equal number of repeated and random sequences. Reaction times (RTs) to implicitly learned and random sequences were compared between groups using ANOVAs and post hoc t-tests. A speed-accuracy trade-off was excluded by analogous analysis of accuracy scores. An interaction was observed between whether responses were to learned or random sequences and the stimulation group. Post hoc analyses revealed a preferential slowing of RTs to implicitly learned sequences in the group receiving CB-TDCS. Our findings provide evidence that CB function can be modulated through transcranial application of a weak electrical current, that the CB and M1 cortex perform separable functions in the task, and that the CB plays a specific role in motor sequence learning during implicit motor sequence learning.

Deep brain stimulation of the ventrointermediate nucleus of the thalamus to treat essential tremor improves motor sequence learning.

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38-81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM-DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM-DBS was on or off (F[1,18] = 7.89, p = .012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p = .031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p = .027). These results demonstrate the beneficial effects of VIM-DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning.

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

BACKGROUND: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. OBJECTIVES: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. RESULTS: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. CONCLUSIONS: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.

Factors associated with long-term impact on informal caregivers during Alzheimer's disease dementia progression: 36-month results from GERAS.

OBJECTIVE: To identify, in caregivers of patients with Alzheimer's disease (AD) dementia, factors associated with subjective (personal, physical, emotional, and social) and objective (informal caregiver time and costs) caregiver burden. DESIGN: Prospective longitudinal European observational study: post-hoc analysis. SETTING: Clinic. PARTICIPANTS: Community-dwelling patients in France and Germany aged ≥ 55 years (n = 969) with probable AD and their informal caregivers. MEASUREMENTS: Mini-Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), 12-item Neuropsychiatric Inventory (NPI-12), Zarit Burden Interview (ZBI), informal caregiver basic and instrumental ADL hours (Resource Utilization in Dementia instrument), and informal caregiver costs. Mixed-effect models of repeated measures (MMRM) were run, including baseline and time-dependent covariates (change from baseline [CFB] to 18 months in MMSE, ADCS-ADL, and NPI-12 scores) associated with CFB in ZBI score/informal caregiver time over 36 months (analyzed using linear regression models) and informal caregiver costs over 36 months (analyzed using generalized linear models). RESULTS: Greater decline in patient function (ADCS-ADL) over 18 months was associated with increased subjective caregiver burden (ZBI), hours, and costs over 36 months. Increased behavioral problems (NPI-12) over 18 months also negatively impacted ZBI. Cognitive decline (MMSE) over 18 months did not affect change in caregiver burden. CONCLUSIONS: Long-term informal caregiver burden was driven by worsening functional abilities and behavioral symptoms but not cognitive decline, over 18 months in community-dwelling patients with AD dementia. Identifying the drivers of caregiver burden could highlight areas in which interventions may benefit both caregivers and patients.

Older and wiser: age differences in susceptibility to investment fraud: the protective role of emotional intelligence.

There have been inconsistent results regarding whether older adults are more vulnerable to fraud than younger adults. The two main goals of this study were to investigate the claim that there is an age-related vulnerability to fraud and to examine whether emotional intelligence (EI) may be associated with fraud susceptibility. Participants (N = 281; 18-82 years; M = 53.4) were recruited via Amazon's Mechanical Turk and completed measures of EI, decision-making, and scam susceptibility. Participants who scored higher on "ability" EI were less susceptible to scams. The "younger" group (M = 2.50, SD = 1.06) was more susceptible to scams than the "older" group, p <.001, d = 0.56, while the "older" group (M = 4.64, SD = 1.52) reported the scams as being more risky than the "younger" group, p =.002, d = 0.37. "Older" participants were more sensitive to risk, less susceptible to persuasion, and had higher than average emotional understanding. Emotional understanding was found to be a partial mediator for age-related differences in scam susceptibility and susceptibility to persuasion.

Hand function, not proximity, biases visuotactile integration later in object processing: An ERP study.

Behavioral studies document a functional hand proximity effect: objects near the palm, but not the back of the hand, affect visual processing. Although visuotactile bimodal neurons integrate visual and haptic inputs, their receptive fields in monkey cortex encompass the whole hand, not just the palm. Using ERPs, we investigated whether hand function influenced the topology of integrated space around the hand. In a visual detection paradigm, target and non-target stimuli appeared equidistantly in front or in back of the hand. Equivalent N1 amplitudes were found for both conditions. P3 target versus non-target amplitude differences were greater for palm conditions. Hand proximity biased processing of visual targets equidistant from the hand early in processing. However, hand function biases emerged later when targets were selected for potential action. Thus, early hand proximity effects on object processing depend on sensory-reliant neural responses, whereas later multisensory integration depend more on the hand's functional expertise.

Learning of novel semantic relationships via sudden comprehension is associated with a hippocampus-independent network.

Sudden comprehension-or insight-during problem-solving can enhance learning, but the underlying neural processes are largely unknown. We investigated neural correlates of learning from sudden comprehension using functional magnetic resonance imaging and a verbal problem-solving task. Solutions and "solutions" to solvable and unsolvable verbal problems, respectively, were presented to induce sudden comprehension or continued incomprehension. We found activations of the hippocampus, medial prefrontal cortex (mPFC), amygdala, and striatum during sudden comprehension. Notably, however, mPFC and temporo-parietal neocortical structures rather than the hippocampus were associated with later learning of suddenly comprehended solutions. Moreover, difficult compared to easy sudden comprehension elicited midbrain activations and was associated with successful learning, pointing to learning via intrinsic reward. Sudden comprehension of novel semantic associations may constitute a special case of long-term memory formation primarily mediated by the mPFC, expanding our knowledge of its role in prior-knowledge-dependent memory.

Long-term outcomes of semi-implantable functional electrical stimulation for central drop foot.

BACKGROUND: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. METHODS: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. RESULTS: We found a main effect of stimulation on both maximum (p < 0.001) and comfortable gait velocity (p < 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p < 0.001), with post hoc testing revealing an increase from T1 to T2 (p < 0.001), which was maintained at T3 (p < 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p < 0.001) and was independent of gait speed but correlated with overall QoL (p < 0.001). CONCLUSIONS: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.

Resource Use and Cost of Alzheimer's Disease in France: 18-Month Results from the GERAS Observational Study.

BACKGROUND: There is little longitudinal data on resource use and costs associated with Alzheimer's disease (AD) in France. OBJECTIVES: To evaluate resource use and societal costs associated with AD in a French cohort of patients and their caregivers and the effect of patient cognitive decline on costs over an 18-month period. METHODS: Community-dwelling patients with mild, moderate, or moderately severe/severe AD dementia (n = 419) were followed-up for 18 months. Total societal costs were estimated by applying 2010 unit costs to resource use, including outpatient visits, hospital days, institutionalization, and caregiver hours. Cognitive function was assessed by Mini-Mental State Examination scores. RESULTS: Mean cumulative total costs over the 18-month period were €24,140 for patients with mild AD dementia, €34,287 for those with moderate AD dementia, and €44,171 for those with moderately severe/severe AD dementia (P < 0.001; ANOVA comparison between severity groups). The biggest contributor to total societal costs was caregiver informal care (>50% of total costs at all stages of AD dementia). Cognitive decline (≥3-point decrease in Mini-Mental State Examination score or institutionalization) was associated with a 12.5% increase in total costs (P = 0.02). Significant differences were observed across severity groups for caregiver time (P < 0.001); mean monthly caregiver time increased at each time point over the 18 months in each severity group. CONCLUSIONS: Increasing severity of AD dementia in France is associated with increased use of resources as well as increased total societal and patient costs; informal care was the greatest cost contributor. Clinically meaningful cognitive decline is associated with significantly increased costs.

Attention orienting near the hand following performed and imagined actions.

Recent studies have documented that the hand's ability to perform actions affects the visual processing and attention for objects near the hand, suggesting that actions may have specific effects on visual orienting. However, most research on the relation between spatial attention and action focuses on actions as responses to visual attention manipulations. The current study examines visual attention immediately following an executed or imagined action. A modified spatial cuing paradigm tested whether a brief, lateralized hand-pinch performed by a visually hidden hand near the target location, facilitated or inhibited subsequent visual target detection. Conditions in which hand-pinches were fully executed (action) were compared to ones with no hand-pinch (inaction) in Experiment 1 and imagined pinches (imagine) in Experiment 2. Results from Experiment 1 indicated that performed hand pinches facilitated rather than inhibited subsequent detection responses to targets appearing near the pinch, but target detection was not affected by inaction. In Experiment 2, both action and imagined action conditions cued attention and facilitated responses, but along differing time courses. These results highlight the ongoing nature of visual attention and demonstrate how it is deployed to locations even following actions.

Feeling but not seeing the hand: Occluded hand position reduces the hand proximity effect in ERPs.

The hand proximity effect (nearby hands influence visual processing) reflects the integration of vision and proprioception for upcoming action; it is reduced when hand position is occluded. In an ERP study, we investigate whether hand proximity, without vision of the hand, accentuates the processing of stimuli requiring actions (targets) early (N1) and later (P3) in processing. In a go/no-go paradigm, participants viewed stimuli between two panels with hands placed near or far from stimuli. Occlusion of the hand eliminated near-hand target vs. non-target differentiation of the N1; amplification of near-hand target amplitudes emerged at the P3. Visual hand location appears necessary to draw visual attention to intended-action objects to integrate body and visual information early in processing. The integration of visual stimulus information and hand position from proprioception appears later in processing, indicating greater reliance on cognitive systems for discriminating the task-relevance of a stimulus.

Potential cost savings to be made by slowing cognitive decline in mild Alzheimer's disease dementia using a model derived from the UK GERAS observational study.

BACKGROUND: Given the high costs associated with the care of those with Alzheimer's disease (AD) dementia, we examined the likely impact of a reduction in the rate of cognitive decline upon cost outcomes associated with this disease. METHODS: Using the group of patients with mild AD dementia from the GERAS study, generalised linear modelling (GLM) was used to explore the relationship between change in cognition as measured using the Mini-Mental State Examination (MMSE) and UK overall costs (health care and social care costs, and total societal costs) associated with AD dementia. RESULTS: A total of 200 patients with mild AD dementia were identified. Least squares mean (LSM) ± standard error (SE) reduction in MMSE score was 3.6 ± 0.4 points over 18 months. Using GLM it was possible to calculate that this worsening in cognition was associated with an 8.7% increase in total societal costs, equating to an increase of approximately £2200 per patient over an 18-month period. If the rate of decline in cognition was reduced by 30% or 50%, the associated savings in total societal costs over 18 months would be approximately £670 and £1100, respectively, of which only £110 and £180, respectively, could be attributed to a saving of health care costs. CONCLUSION: This study demonstrates that there are potential savings to be made in the care of patients with AD dementia through reducing the rate of cognitive decline. A reduction in wider societal costs is likely to be the main contributor to these potential savings, and need to be further evaluated when intervention costs and cost offsets can be measured.

It's Not All About the Face: Variability Reveals Asymmetric Obligatory Processing of Faces and Bodies in Whole-Body Contexts.

Researchers have sought to understand the specialized processing of faces and bodies in isolation, but recently they have considered how face and body information interact within the context of the whole body. Although studies suggest that face and body information can be integrated, it remains an open question whether this integration is obligatory and whether contributions of face and body information are symmetrical. In a selective attention task with whole-body stimuli, we focused attention on either the face or body and tested whether variation in the irrelevant part could be ignored. We manipulated orientation to determine the extent to which inversion disrupted obligatory face and body processing. Obligatory processing was evidenced as performance changes in discrimination that depended on stimulus orientation when the irrelevant region varied. For upright but not inverted face discrimination, participants could not ignore body posture variation, even when it was not diagnostic to the task. However, participants could ignore face variation for upright body posture discrimination but not for inverted posture discrimination. The extent to which face and body information necessarily influence each other in whole-body contexts appears to depend on both domain-general attentional and face- or body-specific holistic processing mechanisms.

Novelty seeking and reward dependence-related large-scale brain networks functional connectivity variation during salience expectancy.

A salience network (SN) anchored in the anterior insula (AI) and dorsal anterior cingulate cortex (dACC) plays a key role in switching between brain networks during salience detection and attention regulation. Previous fMRI studies have associated expectancy behaviors and SN activation with novelty seeking (NS) and reward dependence (RD) personality traits. To address the question of how functional connectivity (FC) in the SN is modulated by internal (expectancy-related) salience assignment and different personality traits, 68 healthy participants performed a salience expectancy task using functional magnetic resonance imaging, and psychophysiological interaction analysis (PPI) was conducted to determine salience-related connectivity changes during these anticipation periods. Correlation was then evaluated between PPI and personality traits, assessed using the temperament and character inventory of 32 male participants. During high salience expectancy, SN-seed regions showed reduced FC to visual areas and parts of the default mode network, but increased FC to the central executive network. With increasing NS, participants showed significantly increasing disconnection between right AI and middle cingulate cortex when expecting high-salience pictures as compared to low-salience pictures, while increased RD also predicted decreased right dACC and caudate FC for high salience expectancy. Our findings suggest a direct link between personality traits and internal salience processing mediated by differential network integration of the SN. SN activity and coordination may therefore be moderated by novelty seeking and reward dependency personality traits, which are associated with risk of addiction. Hum Brain Mapp 38:4064-4077, 2017. © 2017 Wiley Periodicals, Inc.

Factors Influencing the Cardiovascular Response to Subanesthetic Ketamine: A Randomized, Placebo-Controlled Trial.

Background: The increasing use of ketamine as a potential rapid-onset antidepressant necessitates a better understanding of its effects on blood pressure and heart rate, well-known side effects at higher doses. For the subanesthetic dose used for depression, potential predictors of these cardiovascular effects are important factors influencing clinical decisions. Since ketamine influences the sympathetic nervous system, we investigated the impact of autonomic nervous system-related factors on the cardiovascular response: a genetic polymorphism in the norepinephrine transporter and gender effects. Methods: Blood pressure and heart rate were monitored during and following administration of a subanesthetic dose of ketamine or placebo in 68 healthy participants (mean age 26.04 ±5.562 years) in a double-blind, randomized, controlled, parallel-design trial. The influences of baseline blood pressure/heart rate, gender, and of a polymorphism in the norepinephrine transporter gene (NET SLC6A2, rs28386840 [A-3081T]) on blood pressure and heart rate changes were investigated. To quantify changes in blood pressure and heart rate, we calculated the maximum change from baseline (ΔMAX) and the time until maximum change (TΔMAX). Results: Systolic and diastolic blood pressure as well as heart rate increased significantly upon ketamine administration, but without reaching hypertensive levels. During administration, the systolic blood pressure at baseline (TP0Sys) correlated negatively with the time to achieve maximal systolic blood pressure (TΔMAXSys, P<.001). Furthermore, women showed higher maximal diastolic blood pressure change (ΔMAXDia, P<.001) and reached this peak earlier than men (TΔMAXDia, P=.017) at administration. NET rs28386840 [T] carriers reached their maximal systolic blood pressure during ketamine administration significantly earlier than [A] homozygous (TΔMAXSys, P=.030). In a combined regression model, both genetic polymorphism and TP0Sys were significant predictors of TΔMAXSys (P<.0005). Conclusions: Subanesthetic ketamine increased both blood pressure and heart rate without causing hypertensive events. Furthermore, we identified gender and NET rs28386840 genotype as factors that predict increased cardiovascular sequelae of ketamine administration in our young, healthy study population providing a potential basis for establishing monitoring guidelines.

How useful is the EQ-5D in assessing the impact of caring for people with Alzheimer's disease?

BACKGROUND: The impact on informal caregivers of caring for people with Alzheimer's disease (AD) dementia can be substantial, but it remains unclear which measures(s) best assess such impact. Our objective was to use data from the GERAS study to assess the ability of the EuroQol 5-dimension questionnaire (EQ-5D) to measure the impact on caregivers of caring for people with AD dementia and to examine correlations between EQ-5D and caregiver burden. METHODS: GERAS was a prospective, non-interventional cohort study in community-dwelling patients with AD dementia and their informal caregivers. The EQ-5D and Zarit Burden Interview (ZBI) were used to measure health-related quality of life and caregiver burden, respectively. Resource-use data collected included caregiver time spent with the patient on activities of daily living (ADL). Spearman correlations were computed between EQ-5D scores, ZBI scores, and time spent on instrumental ADL (T-IADL) at baseline, 18 months, and for 18-month change scores. T-IADL and ZBI change scores were summarized by EQ-5D domain change category (better/stable/worse). RESULTS: At baseline, 1495 caregivers had mean EQ-5D index scores of 0.86, 0.85, and 0.82, and ZBI total scores of 24.6, 29.4, and 34.1 for patients with mild, moderate, and moderately severe/severe AD dementia, respectively. Change in T-IADL showed a stronger correlation with change in ZBI (0.12; P < 0.001) than with change in EQ-5D index score (0.02; P = 0.546) although both correlations were very weak. Worsening within EQ-5D domains was associated with increases in ZBI scores, although 68%-90% of caregivers remained stable within each EQ-5D domain. There was no clear pattern for change in T-IADL by change in EQ-5D domain. CONCLUSIONS: EQ-5D may not be the optimum measure of the impact of caring for people with AD dementia due to its focus on physical health. Alternative measures need further investigation.

Costs and quality of life in community-dwelling patients with Alzheimer's disease in Spain: results from the GERAS II observational study.

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 <0.001 between groups). Caregiver informal care costs comprised most of the total societal costs and differed significantly between groups (€1050, €1239, €1580, respectively; p value = 0.013), whereas patient healthcare costs did not. Across AD dementia severity groups, patient HRQoL (measured by proxy) decreased significantly (p value <0.001), caregiver subjective burden significantly increased (p value <0.001) and caregiver HRQoL was similar. CONCLUSIONS: Societal costs associated with AD in Spain were largely attributable to caregiver informal care costs and increased with increasing AD dementia severity.