Clock Drawing Test: Types of Errors and Accuracy in Early Cognitive Screening.

BACKGROUND: Clock Drawing Test (CDT) is a commonly used screening tool for cognitive disorders, known for its ease of administration and scoring. Despite frequent use by clinicians, CDT is criticized for its poor predictive value in mild cases of impairment. OBJECTIVE: To evaluate CDT as a screening tool for early stage of cognitive impairment in biomarker-verified Alzheimer's disease (AD) and depressive disorder (DD). METHODS: We analyzed CDT of 172 patients with verified AD, 70 patients with DD, in whom neurodegenerative disorder was excluded using cerebrospinal fluid biomarkers, and 58 healthy older adults. CDT was scored using the semi-quantitative (Shulman) and itemized criteria (adapted from Mendez). RESULTS: Logistic regression showed that for both DD and AD patients with high Mini-Mental State Examination (MMSE) scores (27 and above) the significant predicting variable is uneven number spacing. As MMSE deteriorates (24-26 points), an additional error of setting clock hands is predictive of the disease. In the low MMSE condition, CDT showed an acceptable discrimination for AD (AUC itemized 0.740, Shulman 0.741) and DD (AUC itemized 0.827, Shulman 0.739) using both scoring methods. In the high MMSE condition, discrimination rates were acceptable using itemized scoring but poor using Shulman scoring for both AD (AUC itemized 0.707, Shulman 0.677) and DD (AUC itemized 0.755, Shulman 0.667) groups. CONCLUSION: Ideally, modern diagnostic process should take place before the cognitive performance drops beneath the healthy range. This makes CDT of little use when screening patients with very mild cognitive deficits.

An accurate fully automated panel of plasma biomarkers for Alzheimer's disease.

INTRODUCTION: There is a great need for fully automated plasma assays that can measure amyloid beta (Aß) pathology and predict future Alzheimer's disease (AD) dementia. METHODS: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aß42/Aß40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. RESULTS: The best biomarker for discriminating Aß-positive versus Aß-negative participants was Aß42/Aß40 (are under the curve [AUC] 0.83-0.87). Combining Aß42/Aß40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aß42/Aß40 in MCI (AUC 0.87). DISCUSSION: The high accuracies for Aß pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.

Quantitative analysis of regional distribution of tau pathology with 11C-PBB3-PET in a clinical setting.

PURPOSE: The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET. MATERIALS AND METHODS: A total of 23 memory clinic outpatients with recent decline of episodic memory were examined using 11C-PBB3-PET. Pittsburg compound B (11C-PIB) PET was available for 17, 18F-flurodeoxyglucose (18F-FDG) PET for 16, and cerebrospinal fluid (CSF) protein levels for 11 patients. CSF biomarkers were considered abnormal based on Aß42 (< 600 ng/L) and t-tau (> 450 ng/L). The PET biomarkers were classified as positive or negative using statistical parametric mapping (SPM) analysis and visual assessment. Using the amyloid/tau/neurodegeneration (A/T/N) scheme, patients were grouped as within the AD continuum, SNAP, and BN based on amyloid and neurodegeneration status. The 11C-PBB3 load detected by PET was compared among the groups using both atlas-based and voxel-wise analyses. RESULTS: Seven patients were identified as within the AD continuum, 10 SNAP and 6 BN. In voxel-wise analysis, significantly higher 11C-PBB3 binding was observed in the AD continuum group compared to the BN patients in the cingulate gyrus, tempo-parieto-occipital junction and frontal lobe. Compared to the SNAP group, patients within the AD continuum had a considerably increased 11C-PBB3 uptake in the posterior cingulate cortex. There was no significant difference between SNAP and BN groups. The atlas-based analysis supported the outcome of the voxel-wise quantification analysis. CONCLUSION: Our results suggest that 11C-PBB3-PET can effectively analyze regional tau load and has the potential to differentiate patients in the AD continuum group from the BN and SNAP group.

Emotion induction in young and old persons on watching movie segments: Facial expressions reflect subjective ratings.

Film clips are established to induce or intensify mood states in young persons. Fewer studies address induction of mood states in old persons. Analysis of facial expression provides an opportunity to substantiate subjective mood states with a psychophysiological variable. We investigated healthy young (YA; n = 29; age 24.4 ± 2.3) and old (OA; n = 28; age 69.2 ± 7.4) participants. Subjects were exposed to film segments validated in young adults to induce four basic emotions (anger, disgust, happiness, sadness). We analyzed subjective mood states with a 7-step Likert scale and facial expressions with an automated system for analysis of facial expressions (FaceReader™ 7.0, Noldus Information Technology b.v.) for both the four target emotions as well as concomitant emotions. Mood expressivity was analysed with the Berkeley Expressivity Questionnaire (BEQ) and the Short Suggestibility Scale (SSS). Subjective mood intensified in all target emotions in the whole group and both YA and OA subgroups. Facial expressions of mood intensified in the whole group for all target emotions except sadness. Induction of happiness was associated with a decrease of sadness in both subjective and objective assessment. Induction of sadness was observed with subjective assessment and accompanied by a decrease of happiness in both subjective and objective assessment. Regression analysis demonstrated pre-exposure facial expressions and personality factors (BEQ, SSS) to be associated with the intensity of facial expression on mood induction. We conclude that mood induction is successful regardless of age. Analysis of facial expressions complement self-assessment of mood and may serve as a means of objectification of mood change. The concordance between self-assessment of mood change and facial expression is modulated by personality factors.

Comparison of MRI-based and PET-based image pre-processing for quantification of 11C-PBB3 uptake in human brain.

PURPOSE: Quantification of tau load using 11C-PBB3-PET has the potential to improve diagnosis of neurodegenerative diseases. Although MRI-based pre-processing is used as a reference method, not all patients have MRI. The feasibility of a PET-based pre-processing for the quantification of 11C-PBB3 tracer was evaluated and compared with the MRI-based method. MATERIALS AND METHODS: Fourteen patients with decreased recent memory were examined with 11C-PBB3-PET and MRI. The PET scans were visually assessed and rated as either PBB3(+) or PBB3(-). The image processing based on the PET-based method was validated against the MRI-based approach. The regional uptakes were quantified using the Mesial-temporal/Temporoparietal/Rest of neocortex (MeTeR) regions. SUVR values were calculated by normalizing to the cerebellar reference region to compare both methods within the patient groups. RESULTS: Significant correlations were observed between the SUVRs of the MRI-based and the PET-based methods in the MeTeR regions (rMe=0.91; rTe=0.98; rR=0.96; p<0.0001). However, the Bland-Altman plot showed a significant bias between both methods in the subcortical Me region (bias: -0.041; 95% CI: -0.061 to -0.024; p=0.003). As in the MRI-based method, the 11C-PBB3 uptake obtained with the PET-based method was higher for the PBB3(+) group in each of the cortical regions and for the whole brain than for the PBB3(-) group (PET-basedGlobal: 1.11 vs. 0.96; Cliff's Delta (d)=0.68; p=0.04; MRI-basedGlobal: 1.11 vs. 0.97; d=0.70; p=0.03). To differentiate between positive and negative scans, Youden's index estimated the best cut-off of 0.99 from the ROC curve with good accuracy (AUC: 0.88±0.10; 95% CI: 0.67-1.00) and the same sensitivity (83%) and specificity (88%) for both methods. CONCLUSION: The PET-based pre-processing method developed to quantify the tau burden with 11C-PBB3 provided comparable SUVR values and effect sizes as the MRI-based reference method. Furthermore, both methods have a comparable discrimination accuracy between PBB3(+) and PBB3(-) groups as assessed by visual rating. Therefore, the presented PET-based method can be used for clinical diagnosis if no MRI image is available.

Seizures associated with antibodies against cell surface antigens are acute symptomatic and not indicative of epilepsy: insights from long-term data.

BACKGROUND: Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called "(auto)immune epilepsy." The concept of "acute symptomatic seizures" may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses. METHODS: Retrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years. RESULTS: Patients had surface antibodies against the N-methyl-D-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P < 0.001) and terminal seizure-freedom (80% vs. 7%, P < 0.001) more frequently. The time to first and terminal seizure-freedom and the time to freedom from ASM were shorter in the surface antibody group (Kaplan-Meier curves: P < 0.0001 for first seizure-freedom; P < 0.0001 for terminal seizure-freedom; P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time. CONCLUSION: Seizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses.

[Dementia with Lewy bodies]. / Demenz mit Lewy-Körpern.

A dementia syndrome is often associated with parkinsonoid extrapyramidal motor symptoms. Established consensus criteria allow the diagnosis of Lewy body dementia - however, this diagnosis based on clinical criteria does not exclude the diagnosis of dementia of different etiology. In everyday clinical practice, mixed forms with concomitant Alzheimer's disease or vascular encephalopathy do frequently occur.

On the conundrum of cognitive impairment due to depressive disorder in older patients.

OBJECTIVES: Depressive symptoms and cognitive impairment often concur in older persons. Differentiating the cause of cognitive impairment in older persons with Depressive Disorder (DD) from other diseases such as Alzheimer's Disease (AD) is challenging. The goal of this study was to characterize cognitive impairment in older persons with DD. DESIGN: Cross-sectional retrospective observational clinical cohort study using patient records from 2014 to 2018. SETTING: Gerontopsychiatric services of Ulm University at Bezirkskrankenhaus Günzburg serving as primary psychiatric care institution and tertiary referral center for psychiatric care for older persons. PARTCIPANTS: DD was diagnosed according to ICD-10 criteria. When indicated by the medical history or neuropsychological assessment further diagnostic procedures were initiated. Cerebrospinal fluid (CSF) tap was routinely the first additional procedure. If patients did not consent to CSF tap or contraindications were present, 18F-fluordesoxyglucose-PET (FDG-PET) or Amyloid-PET (Am-PET) were performed. MATERIALS AND METHODS: Extensive neuropsychological test battery to assess cognitive profile. RESULTS: 457 subjects were diagnosed with DD (DD-all; age 50-94; 159 males, 298 females). Biomarkers were assessed in 176 persons; in 90 of these subjects AD-biomarkers were negative (DD-BM-; age 54-89; 40 males, 50 females), and in 86 subjects at least one biomarker was compatible with AD (DD-BM+; age 60-90; 31 males, 55 females). Cognitive performance was below healthy controls (HC; n = 56; age 50-80; 30 males, 26 females) for all groups of patients with DD. With case-control matching of HC and DD-BM- we find that executive functions are impaired in about one out of three and delayed recall in about two out of three patients with DD. CONCLUSION: Cognitive impairment is frequent in older persons with DD. Cognitive profile in older patients with DD without and with biomarkers of AD is not distinguishable. Therefore, cognitive impairment due to DD should be diagnosed after exclusion of comorbid AD.

Cognitive profiles in persons with depressive disorder and Alzheimer's disease.

Alzheimer's disease and depressive disorder are frequent in old age. Both may be associated with depressed mood and cognitive impairment. Therefore, finding a strategy to clarify the diagnosis underlying subjective complaints of impaired cognition and depressed mood in older persons is of utmost interest. We conducted a cross-sectional retrospective observational clinical cohort study using patient records from 2014 to 2018. From 3758 patients, we included patients aged 60 years and older with a Mini-Mental-Status Examination score of 24 and above. Final analysis included all patients in whom Alzheimer's disease biomarker analysis was performed (cerebrospinal fluid markers of Alzheimer's disease or positron emission tomography imaging; n = 179) and patients with depressive disorder in whom Alzheimer's disease was ruled out by analysis of biomarkers suggestive of Alzheimer's disease (n = 70). With case-control matching for age, education and gender, performance of patients with Alzheimer's disease was worse in acquisition, consolidation and recall of verbal information and false-positive answers. None of the results, however, sufficed to differentially diagnose individual patients with Alzheimer's disease or depressive disorder. With more severe symptoms of depression, patients with biomarker-verified Alzheimer's disease performed worse in executive testing but were not additionally impaired in verbal episodic memory performance. We conclude that distinguishing between Alzheimer's disease and depressive disorder is unreliable on clinical grounds and behavioural testing alone. Diagnosing the cause of subjective complaints about deteriorating cognitive function or depressed mood requires additional biomarker assessment, whereas cognitive assessment is needed to define appropriate targets of symptomatic treatment in patients with Alzheimer's disease and depressive disorder.

News and Commercials: Binding Deficits for Complex Information in Schizophrenia.

Memory for complex content is severely impaired in patients with schizophrenia spectrum disorders, which might make processing of daily information such as news and commercials particularly challenging. The goal of the present study was to assess the impairment of everyday memory in patients with schizophrenia. Healthy controls (HC) and patients with schizophrenia (SZ) were asked to watch a selection of six news segments and six commercials and complete a recognition task on the content of these video clips. All participants completed a neuropsychological test battery comprising measures of attention, working and episodic memory, and executive function. The total number of correctly recognized items was significantly lower in the SZ group. In contrast, the number of false recognitions was alike in both news and commercials paradigm. We conclude that memory in patients with schizophrenia is more prone to omissions than distortions for complex everyday stimuli. The results offer further support for impaired binding in SZ patients. Memory in SZ suffices to reject false multi-feature items on grounds of identifying at least one feature as incorrect but does not suffice to recall all features of a complex item and affirm it as correct.

Everyday Memory in Healthy Aging: Porous but Not Distorted.

Most studies targeting age-association of memory functions report a decline in recognition hits and an increase in false alarms. The goal of the present study was to assess these findings in tasks with day-to-day relevance. We investigated healthy young (YA; age 26.90 ± 3.55 years) and old (OA; age 69.80 ± 5.85 years) adults. Participants were asked to watch six news and six commercials and complete a recognition task relating to the information presented in the videos. OA had a lower hit rate in both news and commercials compared to YA. However, the number of false alarms (FA) was the same in both age groups. Applying signal detection theory, we found age differences in discriminability for both news and commercials paradigm. The groups showed no differences in bias and both chose a liberal answering tendency. We interpret our finding as a result of complex recognition items in an ecologically valid task. Multi-feature items offer an advantage in correct rejection-it is enough to know that at least one feature of an item is false. This benefit does not extend to hits, where all features of an item need to be recognized. This indicates that recognition memory of naturalistic stimuli in OA is porous, but not distorted.

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

BACKGROUND: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. METHODS AND FINDINGS: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.

Cognitive function and the agreement between self-reported and accelerometer-accessed physical activity.

BACKGROUND: Numerous studies have reported weak or moderate correlations between self-reported and accelerometer-assessed physical activity. One explanation is that self-reported physical activity might be biased by demographic, cognitive or other factors. Cognitive function is one factor that could be associated with either overreporting or underreporting of daily physical activity. Difficulties in remembering past physical activities might result in recall bias. Thus, the current study examines whether the cognitive function is associated with differences between self-reported and accelerometer-assessed physical activity. METHODS: Cross-sectional data from the population-based Activity and Function in the Elderly in Ulm study (ActiFE) were used. A total of 1172 community-dwelling older adults (aged 65-90 years) wore a uniaxial accelerometer (activPAL unit) for a week. Additionally, self-reported physical activity was assessed using the LASA Physical Activity Questionnaire (LAPAQ). Cognitive function was measured with four items (immediate memory, delayed memory, recognition memory, and semantic fluency) from the Consortium to Establish a Registry for Alzheimer's Disease Total Score (CERAD-TS). RESULTS: Mean differences of self-reported and accelerometer-assessed physical activity (MPA) were associated with cognitive function in men (rs = -.12, p = .002) but not in women. Sex-stratified multiple linear regression analyses showed that MPA declined with high cognitive function in men (ß = -.13; p = .015). CONCLUSION: Results suggest that self-reported physical activity should be interpreted with caution in older populations, as cognitive function was one factor that explained the differences between objective and subjective physical activity measurements.

Everyday false memories in older persons with depressive disorder.

Generally we tend to think that memory in daily living is complete and accurate in healthy persons. However, current memory research has revealed inconspicuous memory faults. Rarely omissions and distortions of memory are researched with tasks resembling everyday life. We investigated healthy older control subjects (HC) and patients with depressive disorder (DD). Cognitive function was assessed with a comprehensive neuropsychological test battery and mood with the Montgomery-Asberg Depression Scale (MADRS). We assessed everyday veridical and distorted memories on showing participants original news and commercials. In most aspects of attention, executive functions, and memory, patients with DD performed worse than HC. Regarding memory content on viewing news or commercials the difference between patients with DD and HC was more pronounced for false memory content than for veridical memory content. Linear regression analysis showed the extent of false memory content being associated with mental flexibility as assessed with the Trail Making Test and mood as assessed with the MADRS for both information obtained on viewing news and commercials. Increase of false memories impedes overall accuracy of memory more than decrease of veridical memories in older persons with depressive disorder. Diminished executive functions and depressive mood partly explain these memory distortions.

Positive mood on negative self-statements: paradoxical intervention in geriatric patients with major depressive disorder.

OBJECTIVES: Mood regulation is said to be age-specific. Negative self-statements (NST) are used to induce negative mood. However, little is known about NST in older persons and geriatric patients with major depressive disorder. METHOD: We investigated healthy young (YC) and older (OC) control subjects and older patients with major depressive disorder (OP). Subjects were exposed to NST subsequent to baseline assessment comprising psychological and psychometric tests. Preferences for emotionally salient stimuli were measured with an eye-tracking task. RESULTS: Mood in YC shifted towards depressive mood or remained stable on NST. In OC and more so in OP some subjects responded paradoxically subsequent to NST with mood being more positive than at baseline. Extent and direction of mood change correlated with prevailing mood at baseline and total score in the Hamilton Depression Anxiety Scale. At baseline, YC had a preference for 'happy' stimuli. Subsequent to NST view preference shifted towards 'sad.' In contrast, OC had no preference at baseline but shifted towards 'happy' on NST. CONCLUSIONS: Mood change on NST is age-specific. In geriatric patients with depressive disorder, however, NST may induce a shift towards more positive mood and thus may be used in future as a therapeutic intervention.

Everyday Memory in Patients with Alzheimer's Disease: Fragmentary and Distorted.

BACKGROUND: Errors of omission are an established hallmark of memory impairment in Alzheimer's disease (AD). Much less is known about other memory errors in AD such as false memories. OBJECTIVE: We investigated false memories in healthy elderly controls (HC; n = 23) and patients with AD (n = 20) using real-life tasks of watching news and commercials. METHODS: Participants received a comprehensive neuropsychological assessment and were shown original news and commercials with a subsequent recognition task to assess veridical and false memories. RESULTS: Subjective estimate of the number of errors were alike in HC and patients with AD. However, memory performance in both the news and the commercials task was significantly worse in patients with AD. Trail-Making Test and Symbol-Span Test were significant predictors of false memories on viewing news and commercials. In patients with AD, levels of Aß1 - 42, but not levels of tau-protein were correlated with false memories in both tasks. CONCLUSIONS: Everyday life in patients with AD is impeded not due to the incompleteness of memory but also due to its distortions. Furthermore, it is hindered by the lack of awareness towards these deficits. False memory content in patients with AD is associated with Aß42 levels in the CSF as a surrogate of the overall extent to which the brain has been affected by AD pathology. Future studies will need to address the impact of this duality of memory failure on everyday life of patients with AD and their proxies in greater detail.

Preferences of psychiatric practitioners for core symptoms of major depressive disorder: a hidden conjoint analysis.

According to ICD-10 and DSM-V, symptoms of depressive disorder are considered to be equally important for severity judgment. It was the goal to investigate the weight of selected symptom complexes for severity judgment. In workaday life severity judgment results from an overall impression rather than from calculating severity in different symptom complexes, separately. In fact, the drivers for overall judgment may not be known explicitly to the psychiatrist himself. A method of choice to resolve this is conjoint analysis. Based on the Montgomery-Asberg Depression Scale (MADRS) and the Sheehan Disability Scale (SDS) case vignettes were constructed. Different symptom severity in the domains mood, vegetative symptoms, cognition/inhibition, suicidality, and everyday functioning were worked into the vignettes. Different symptom complexes influence the severity judgment by clinical psychiatrists to a rather different extent. Mood has a greater impact on severity judgment than suicidality, cognition/inhibition, vegetative symptoms, and everyday functioning. We conclude that core complexes of major depressive disorder are valued with different clinical relevance by psychiatrists. Thus, diagnosis and appraisal of therapeutic efficacy are subject to individual preferences of clinical psychiatrists and prevalence and therapeutic efficacy may be over- or under-estimated unless these differences in preferences are taken into account.

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.

INTRODUCTION: In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers. METHODS AND ANALYSIS: All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78. ETHICS AND DISSEMINATION: All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal. TRIAL REGISTRATION NUMBER: EUDRACT 2012-002764-27; Pre-results.

Drug-induced cerebral glucose metabolism resembling Alzheimer's Disease: a case study.

BACKGROUND: With aging of society the absolute number and the proportion of patients with cognitive deficits increase. Multiple disorders and diseases can foster cognitive impairment, e.g., Alzheimer's disease (AD), depressive disorder, or polypharmacy. CASE PRESENTATION: A 74 year old man presented to the Old Age Psychiatry Service with cognitive deficits while being treated for recurrent depressive episodes and essential tremor with Venlafaxine, Lithium, and Primidone. Neuropsychological testing revealed a medio-temporal pattern of deficits with pronounced impairment of episodic memory, particularly delayed recall. Likewise, cognitive flexibility, semantic fluency, and attention were impaired. Positron emission tomography (PET) with fluorodeoxyglucose was performed and revealed a pattern of glucose utilization deficit resembling AD. On cessation of treatment with Lithium and Primidone, cognitive performance improved, particularly episodic memory performance and cognitive flexibility. Likewise, glucose metabolism normalized. Despite normalization of both, clinical symptoms and glucose utilization, the patient remained worried about possible underlying Alzheimer's disease pathology. To rule this out, an amyloid-PET was performed. No cortical amyloid was observed. CONCLUSION: Pharmacological treatment of older subjects may mimic glucose metabolism and clinical symptoms of Alzheimer's disease. In the present case both, imaging and clinical findings, reversed to normal on change of treatment. Amyloid PET is a helpful tool to additionally rule out underlying Alzheimer's disease in situations of clinical doubt even if clinical or other imaging findings are suggestive of Alzheimer's disease.

Factors Associated with Greater Adherence to and Satisfaction with Transdermal Rivastigmine in Patients with Alzheimer's Disease and Their Caregivers.

BACKGROUND/AIMS: Adherence to cholinesterase inhibitors is important in order to maximise treatment efficacy. This study aimed to investigate patient and caregiver factors associated with adherence to and satisfaction with transdermal rivastigmine treatment. METHODS: Sociodemographic, clinical and psychosocial data were collected from 127 patients and their caregivers during the first follow-up visit after prescription. At the second follow-up, data were collected on 110 of the dyads. Adherence to and satisfaction with the treatment were assessed using the Medication Adherence Report Scale and an adapted version of the Alzheimer's Disease Caregiver Preference Questionnaire. RESULTS: 66.2% of the caregivers reported being adherent to, and 77.0% were satisfied with, the patch at the second follow-up. Factors predicting higher adherence at the second follow-up were caregivers' greater frequency of contact with patients, greater satisfaction with the information received about the patch, better tolerability of the patch and living at home with their caregivers. Greater concerns of the caregivers about the patch and the patients' belief in 'other' causes of their Alzheimer's disease predicted a lower adherence at the second follow-up. CONCLUSIONS: Assessing and addressing caregivers' concerns about transdermal rivastigmine, improving doctor-patient/caregiver communication to increase caregiver satisfaction with information about the patch as well as providing education and support around patients' beliefs and tolerability of the patch could improve adherence to transdermal rivastigmine.