[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.

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.

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.

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.

Efficacy of short-term inpatient rehabilitation for dementia patients and caregivers: prospective cohort study.

BACKGROUND/AIMS: The efficacy of nonpharmacological and multicomponent treatments in patients with dementia is under discussion, as is the ongoing debate which endpoints best measure efficacy. METHODS: 194 dyads of dementia patients and their proxies interested in a combined short-term inpatient rehabilitative treatment were assessed in the patients' homes. RESULTS: Analysis showed that cognition in male patients (cognitive part of the Alzheimer's Disease Assessment Scale: p = 0.048) and depressive mood in female patients were improved after treatment at the 3-month follow-up (Geriatric Depression Scale: p = 0.030). Moreover, the burden on male caregivers was reduced (behavioral pathology in Alzheimer's Disease Rating Scale: p = 0.002) at 3 months. CONCLUSION: Combined short-term rehabilitative treatment of patients and psychosocial intervention for caregivers is modestly effective in patients with dementia and their caregivers, but may be subject to gender-specific effects.

Appraising the need for care in Alzheimer's disease.

BACKGROUND: Increasing incidences of dementia necessitate the improvement of supportive measures for patients suffering from this disease and their proxies. Clinicians without psychiatric backgrounds and others involved in appraising the supportive needs of dementia patients, such as those who allocate nursing insurance, base their appraisals on the ability of patients to perform basic and instrumental activities of daily living (B-ADL, iADL). Our aim was to investigate whether a reduced ability of the patient to perform ADL is sufficient to adequately assess the supportive needs of family caregivers. METHODS: Cross-sectional baseline data were obtained from dementia patients and their proxies in the context of a nationwide prospective cohort study on non-pharmacological treatment of dementia. To our knowledge, the present study is the first country-wide study to assess patients and proxies in their domestic surroundings (e.g. Mini-Mental State Examination (MMSE) Behave-AD, B-ADL and iADL for patients; Quality of Life (QOL) and depression of the proxy). RESULTS: Logistic and linear regression analysis show that the allocation of nursing care allowance provided by German mandatory nursing insurance is associated with scores on the B-ADL- and iADL scales, but not with the severity of behavioural symptoms or the supportive time the proxies spend on caring. However, the severity of cognitive and non-cognitive symptoms of dementia patients, correlate with each other and both parameters correlate with the time the proxy spends on caring. The time spent on caring is associated with an increase in depression and a reduction in the quality of life of the proxy. CONCLUSIONS: Basic and instrumental activities of daily living do not sufficiently reflect the perceived burden of care experienced by the proxy who has to cope with the imposition of the dementia patients' behavioural symptoms. When allocating nursing care, patients' behavioural symptoms should also be taken into consideration, because depressive symptoms of proxies are linked to non-cognitive symptoms in dementia patients. To provide better health care, it is necessary to identify and treat psychiatric symptoms in proxies who care for dementia patients as early as possible.

[Dementia in Germany: results of an interdisciplinary expert workshop]. / Demenz in Deutschland--Ergebnisse eines interdisziplinären Expertenworkshops.

In the aging population of Germany the consequences of Dementia for the society and the health care sector are complex and solutions require a multidisciplinary approach. The aim of the two-day interdisciplinary expert conference was to consider dementia from different perspectives, to identify dementia-related problems and to discuss integrative solutions under consideration of complementary therapies. In different working groups the experts developed solutions and recommendations with regards to political need, health care and future research priorities. The present recommendations profited very much from the interdisciplinary participants of the conference and brought together the expertise of different fields resulting in a comprehensive picture about dementia in Germany.

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.

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.

Measuring therapeutic efficacy in patients with Alzheimer's disease: role of instruments.

BACKGROUND/AIMS: Global cognitive scales and meta-analyses thereof are used to appraise therapeutic efficacy over a broad range of disease severity. Clinically, however, different aspects of cognition change in different stages of disease. METHODS: Calculation of effect sizes for single cognitive functions on treatment as assessed by the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental-Status Examination (MMSE), and the Severe Impairment Battery (SIB). In these scales, subdomains of 'cognition', e.g. memory and language, are represented in different proportions. To exemplify the analysis of 'cognition', we used original data of previously published clinical studies with memantine. RESULTS: Depending on dementia severity and on the scale used, the effect size for memory varies between -0.44 and +0.34 and for language between -0.40 and +0.26. CONCLUSION: Beyond interstudy variance, effect sizes for treatment with antidementia drugs are subject to disease stage, instruments used, and interaction thereof. Therefore, clinical interpretation is necessary to appraise therapeutic efficacy in clinical studies and meta-analyses thereof when patients with different severity are included or different instruments are used. Alternatively, severity-adapted endpoints should be used for appraisal and meta-analysis of therapeutic efficacy.

Staging dementia using proxy-reported activities of daily living.

BACKGROUND/AIM: It has been questioned whether cognitive and behavioral scales sufficiently address the impact of dementia on the everyday life of patients. Therefore, other instruments are used, such as scales of activities of daily living (ADL). Our goal was to analyze variables influencing the appraisal of ADL. METHOD: Prospective cohort study on 202 patients with dementia and their proxies. RESULTS: Two clusters of patients were identified. These clusters differed significantly in their constituting variables and all variables that informants reported regarding the patients. However, severity of dementia and other variables were similar in the two clusters. CONCLUSION: We conclude that ratings of basic and instrumental ADL by proxy are modulated by the informants' variables, particularly if these informants are female. Use of ADL scales to assess the impact of dementia or treatment thereof needs to be handled cautiously.

Additive scales in degenerative disease--calculation of effect sizes and clinical judgment.

BACKGROUND: The therapeutic efficacy of an intervention is often assessed in clinical trials by scales measuring multiple diverse activities that are added to produce a cumulative global score. Medical communities and health care systems subsequently use these data to calculate pooled effect sizes to compare treatments. This is done because major doubt has been cast over the clinical relevance of statistically significant findings relying on p values with the potential to report chance findings. Hence in an aim to overcome this pooling the results of clinical studies into a meta-analyses with a statistical calculus has been assumed to be a more definitive way of deciding of efficacy. METHODS: We simulate the therapeutic effects as measured with additive scales in patient cohorts with different disease severity and assess the limitations of an effect size calculation of additive scales which are proven mathematically. RESULTS: We demonstrate that the major problem, which cannot be overcome by current numerical methods, is the complex nature and neurobiological foundation of clinical psychiatric endpoints in particular and additive scales in general. This is particularly relevant for endpoints used in dementia research. 'Cognition' is composed of functions such as memory, attention, orientation and many more. These individual functions decline in varied and non-linear ways. Here we demonstrate that with progressive diseases cumulative values from multidimensional scales are subject to distortion by the limitations of the additive scale. The non-linearity of the decline of function impedes the calculation of effect sizes based on cumulative values from these multidimensional scales. CONCLUSIONS: Statistical analysis needs to be guided by boundaries of the biological condition. Alternatively, we suggest a different approach avoiding the error imposed by over-analysis of cumulative global scores from additive scales.

Gender-dependence of substituted judgment on quality of life in patients with dementia.

BACKGROUND: Substituted judgment asks the proxy to decide what the patient would have decided, had he or she been competent. It is unclear whether substituted judgment of the patient's quality of life can serve as a surrogate measure in patients with dementia. METHODS: 212 patients with dementia and their proxies were interviewed in their homes. Dementia syndrome was characterized with cognitive, non-cognitive and functional scales. Quality of life (QoL) was assessed with the QoL-AD. RESULTS: Substituted judgment of the patient's QoL was unrelated to dementia severity but also correlated with the proxie's own QoL (r = 0.356; p < 0.001). Gender-specific analysis reveals that for male proxies the most important variable is severity of patient's depression (r = -0.895; p = 0.001) while for female proxies it is the proxie's own QoL (r = 0.371; p < 0.001). Subjective burden correlates with the proxie's QoL in females (r = -0.282; p = 0.001) but not in males (r = -0.163, p = 0.161). CONCLUSION: Substituted judgment of the patient's QoL does not correlate with dementia severity. Substituted judgment is subject to proxy-related variables in a gender-dependent fashion and therefore not suited to serve as an appropriate surrogate of the patients' quality of life.

Amyloid beta 1-42 in cerebrospinal fluid is associated with cognitive plasticity.

Cerebrospinal fluid (CSF) total tau-protein (t-tau) and amyloid-beta 1-42 (Abeta(1-42)) have been increasingly included in the diagnostic process of Alzheimer's disease (AD). We aimed to analyze whether these CSF biomarkers correlate with cognitive plasticity as measured by a dynamic recognition test strategy. We assessed 29 elderly individuals (15 with incipient and 14 without AD) from an outpatient memory clinic at a university hospital by a Testing-the-Limits (TtL) based recognition paradigm consisting of a pre-test (baseline) and two post-test conditions with an interposed encoding instruction. We identified a negative association between Abeta(1-42) and the two post-test failure rates, but not with that of the pre-test. Also, none of the standard tests correlates with Abeta 42-1 level. T-tau does not correlate with recognition performance. Our results suggest that Abeta(1-42) could be useful as a state marker for cognitive plasticity.

Assessment of dementia in ethnic minority patients in Europe: a European Alzheimer's Disease Consortium survey.

BACKGROUND: In most European countries the ethnic minority migrant populations are currently reaching an age where dementia becomes an increasingly important issue. There is no European consensus on good clinical practice with these patient groups, who often have special needs and expectations with regard to dementia services. METHODS: A survey was conducted in clinical dementia centers in 15 European countries. Questionnaires focusing on different points in the clinical assessment of dementia in ethnic minority patients were mailed to leading dementia experts of the European Alzheimer's Disease Consortium. RESULTS: Thirty-six centers from 15 countries responded to the survey. Ethnic minority patients were seen on a regular basis in 69% of these centers. The diagnostic evaluation was in accordance with evidence-based clinical guidelines in 84-100% of the centers, but most centers performed cognitive assessment with instruments that are only validated in Western cultures and frequently relied on family members for interpretation. Diagnostic evaluation of the patients was considered to be challenging in 64% of the centers, mainly because of communication problems and lack of adequate assessment tools. In general, there were few indicators of culturally sensitive dementia services in the centers. CONCLUSIONS: Ethnic minority patients are seen on a regular basis in European dementia clinics. Assessment of such patients is difficult for a number of reasons. Results from this study show that the most challenging issues are communication problems and assessment of cognitive function where there is a need to develop specific tests for ethnic minority patients.

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.

Tau-proteins as gender-specific state markers in amnestic mild cognitive impairment.

BACKGROUND/AIMS: Our purpose was to assess whether cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) reflect trait or state of disease in patients with AD and amnestic mild cognitive impairment (aMCI). METHODS: Analysis of CSF levels of A-ß-(1, 42), total tau and phospho-tau-181 (t-tau and p-tau-181), cognitive scaling with the cognitive part of the Alzheimer's Disease Assessment Scale and detailed neuropsychological testing including the California Verbal Learning Test (CVLT) and the Visual Reproduction Test from the Wechsler Memory Scale (WMS). RESULTS: We assessed healthy elderly controls, patients with aMCI (Petersen criteria; n = 62; age 67.9 ± 7.6 years; MMSE score = 28.0 ± 1.6; mean ± standard deviation) and patients with AD (DSM-IV and NINCDS-ADRDA criteria; n = 106; age = 71.8 ± 7.5 years; MMSE score ≥20, 23.7 ± 2.4) from an outpatient memory clinic. In the aMCI subjects, but not in the controls or patients with AD, the CVLT and the WMS scores correlated with the levels of t-tau and p-tau-181. More specifically, the CSF levels of p-tau-181 and t-tau correlated with the CVLT score in females and WMS score in males. CONCLUSIONS: Neurochemical markers of AD are gender-specific state markers in aMCI. This forms the basis for future preventive studies aiming at delaying manifest AD.

Generic quality of life assessment in dementia patients: a prospective cohort study.

BACKGROUND: Quality of life (QoL) is increasingly used to characterize the impact of disease and the efficacy of interventions. METHODS: Prospective cohort study in patients' and proxies' homes with 137 patients with dementia (age 52 to 88; Mini-Mental Status Examination (MMSE) 3 to 28) and their proxies (age 43 to 90). MMSE, Behave-AD, Geriatric Depression Scale (GDS), and Bayer-ADL scale (B-ADL), and the Euroqol (EQ-5D; patient self-rating, proxy self-rating, and proxy-rating of patient). RESULTS: B-ADL impairment and Behave-AD total score increased with dementia severity (Kruskal-Wallis p < 0.001 and p = 0.023, respectively). Patients' self-rated QoL and proxies' self-rated QoL were unrelated to dementia severity (p = 0.148 and p = 0.414, respectively). The difference between patients' self- and proxies'-rating of the patient's QoL correlated with the patient's MMSE (Spearman's rho = -0.434; p < 0.001), even if analysis was constrained to patients with mild AD (rho = -0.328; p = 0.019). The proxies' rating of the patients QoL was not only correlated with cognitive and behavioral symptoms of the patient but also with mood (GDS-score; rho = 0.317; p < 0.001) and cognitive abilities (verbal fluency; rho = 0.209; p < 0.018) of the proxy. CONCLUSION: Proxies' assessment of the patients' QoL is related to the proxies' health, and the difference of patient's and proxie's QoL-rating is correlated with dementia severity even in mild dementia stages. QOL measures use ratings of the individual to assess the impact of symptoms and disorders on everyday life. In dementia patients, however, this impact is not captured since patients' and proxies' self-assessment of their own QoL do not reflect severity of disease whatsoever. Patients' and proxies' influencing variables render the score obtained with generic quality of life assessment meaningless in capturing the impact of dementia. Decisions on initiation or discontinuation of treatment or allocation of other resources for patients with dementia therefore need not depend on generic assessment of quality of life.