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ObjectivesMethodResultsConclusionThis study explores the early identification of rheumatoid arthritis (RA) patients at elevated risk of progression. Haem-oxygenase-1 (HO-1) is a marker of oxidative stress in inflammation. Here, we investigate HO-1 as a biomarker of oxidative stress and its association with clinical disease activity and radiographic progression in RA.Baseline HO-1 was measured sequentially in plasma samples from patients with early rheumatoid arthritis (eRA) (n = 80). Disease Activity Score based on 28-joint count–C-reactive protein, Clinical Disease Activity Index, and total Sharp score were used to evaluate the disease course serially over 2 years. Paired plasma and synovial fluid samples were examined for HO-1 in active established rheumatoid arthritis (esRA) (n = 20). Plasma from healthy control subjects was also included (n = 35).Plasma HO-1 levels were increased in eRA {1373 pg/mL [interquartile range (IQR) 1110–2050]} and esRA [2034 pg/mL (IQR 1630–2923)] compared with controls [1064 pg/mL (IQR 869.5–1378)]. HO-1 plasma levels decreased with treatment. Baseline HO-1 correlated with disease activity and radiographic progression. A strong, linear correlation was found between synovial and plasma HO-1 levels (r = 0.75, p < 0.001).In eRA, plasma levels of HO-1 were increased and correlated with disease and radiographic progression. A baseline measurement of plasma HO-1 levels demonstrated superior performance to currently used clinical and serological disease markers in the prediction of radiographic progression. Plasma HO-1 may function as a first-in-class biomarker of synovial oxidative stress in RA. [ABSTRACT FROM AUTHOR]

Background: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus., Methods: A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG., Results: No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC., Conclusions: Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD., Trial Registration: The study is registered at clinicaltrials.gov (NCT04436341)., (© 2024. The Author(s).)

Background: Patients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB., Objectives: To investigate if IED as measured with ear-EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC)., Methods: In this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear-EEG recordings, each lasting up to 2 days, over a period of 6 months., Results: At baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42-4.61; P-value = 0.001). Most IED occurred at night., Conclusions: Long-term outpatient ear-EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD. Our aim is to investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC)., Methods: In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months., Results: The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 h) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77-5.01, p < 0.001). Most patients with AD (91.7%) showed epileptiform discharges when combining all ear-EEG recordings., Conclusions: Long-term ear-EEG monitoring detects epileptiform discharges in most patients with AD with a three-fold increased spike frequency compared to HC, which most likely originates from the temporal lobes. Since most patients showed epileptiform discharges with multiple recordings, elevated spike frequency should be considered a marker of hyperexcitability in AD., Competing Interests: Declaration of Competing Interest Christian Sandøe Musaeus received an unrestricted grant from T&W engineering. Two authors (Mike Lind Rank, and Martin Christian Hemmsen) who are employees of T&W Engineering contributed to the interpretation and writing of the manuscript. Troels Wesenberg Kjær consults for T&W Engineering., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration., Objective: To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer's disease (AD)., Methods: This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer's disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention., Results: A total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOE ε 4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline -1.16, p = 0.09]., Conclusion: The findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration., Clinical Trial Registration: clinicaltrials.gov, identifier NCT01681602., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frederiksen, Jensen, Høgh, Gergelyffy, Waldemar, Andersen, Gottrup, Vestergaard, Wermuth, Søndergaard, Sellebjerg, Hasselbalch and Simonsen.)

Background: Previous studies have reported that epileptiform activity may be detectible in nearly half of patients with Alzheimer's disease (AD) on long-term electroencephalographic (EEG) recordings. However, such recordings can be uncomfortable, expensive, and difficult. Ear-EEG has shown promising results for long-term EEG monitoring, but it has not been used in patients with AD., Objective: To investigate if ear-EEG is a feasible method for long-term EEG monitoring in patients with AD., Methods: In this longitudinal, single-group feasibility study, ten patients with mild to moderate AD were recruited. A total of three ear-EEG recordings of up to 48 hours three months apart for six months were planned., Results: All patients managed to wear the ear-EEG for at least 24 hours and at least one full night. A total of 19 ear-EEG recordings were performed (self-reported recording, mean: 37.15 hours (SD: 8.96 hours)). After automatic pre-processing, a mean of 27.37 hours (SD: 7.19 hours) of data with acceptable quality in at least one electrode in each ear was found. Seven out of ten participants experienced mild adverse events. Six of the patients did not complete the study with three patients not wanting to wear the ear-EEG anymore due to adverse events., Conclusion: It is feasible and safe to use ear-EEG for long-term EEG monitoring in patients with AD. Minor adjustments to the equipment may improve the comfort for the participants.

Background: The two biomarkers 2-[18F]FDG-PET and cerebrospinal fluid biomarkers are both recommended to support the diagnosis of Alzheimer's disease. However, there is a lack of knowledge for the comparison of the two biomarkers in a routine clinical setting., Objective: The aim was to compare the clinical impact of 2-[18F]FDG-PET and cerebrospinal fluid biomarkers on diagnosis, prognosis, and patient management in patients suspected of Alzheimer's disease., Methods: Eighty-one patients clinically suspected of Alzheimer's disease were retrospectively included from the Copenhagen Memory Clinic. As part of the clinical work-up all patients had a standard diagnostic program examination including MRI and ancillary investigations with 2-[18F]FDG-PET and cerebrospinal fluid biomarkers. An incremental study design was used to evaluate the clinical impact of the biomarkers. First, the diagnostic evaluation was based on the standard diagnostic program, then the diagnostic evaluation was revised after addition of either cerebrospinal fluid biomarkers or 2-[18F]FDG-PET. At each diagnostic evaluation, two blinded dementia specialists made a consensus decision on diagnosis, prediction of disease course, and change in patient management. Confidence in the decision was measured on a visual analogue scale (0-100). After 6 months, the diagnostic evaluation was performed with addition of the other biomarker. A clinical follow-up after 12 months was used as reference for diagnosis and disease course., Results: The two biomarkers had a similar clinical value across all diagnosis when added individually to the standard diagnostic program. However, for the correctly diagnosed patient with Alzheimer's disease cerebrospinal fluid biomarkers had a significantly higher impact on diagnostic confidence (mean scores±SD: 88±11 vs. 82±11, p = 0.046) and a significant reduction in the need for ancillary investigations (23 vs. 18 patients, p = 0.049) compared to 2-[18F]FDG-PET., Conclusion: The two biomarkers had similar clinical impact on diagnosis, but cerebrospinal fluid biomarkers had a more significant value in corroborating the diagnosis of Alzheimer's disease compared to 2-[18F]FDG-PET., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI., Methods: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI., Results: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI., Conclusions: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning., (© 2020 John Wiley & Sons Ltd.)

Background: Several factors may play a role in the ability of patients with Alzheimer's disease to perform activities of daily living (ADL). The aim of this study was to examine the impact of different aspects of physical performance and cognitive functions on ADL in patients suffering from mild-to-moderate Alzheimer's disease., Methods: We conducted secondary analyses on cross-sectional baseline data from the randomized controlled multicentre study "Preserving quality of life, physical health and functional ability in Alzheimer's Disease: The effect of physical exercise" (ADEX). In total, 185 AD patients (76 women and 109 men), with a mean age on 70,4 years, were included. Data from physical performance tests (Astrand cycle test, Timed up & Go (TUG), Sit to Stand test (STS)) and cognitive tests (Mini Mental Status Examination (MMSE), Symbol Digit Modalities Test (SDMT), Stroop Color and Word test (Stroop)) were used. Their associations with ADL, measured on the ADCS-ADL scale was assessed in multivariable regression analyses., Results: SDMT and MMSE had significant, moderate correlations with total ADL (SDMT: r = 0.33, MMSE: r = 0.42) and instrumental ADL (SDMT: r = 0.31, MMSE: r = 0.42), but not with basic ADL. Adjusting for age and sex, the associations between SDMT and MMSE to total ADL and instrumental ADL persisted. No significant associations were found between Astrand, TUG, STS or Stroop and total ADL, basic ADL or instrumental ADL., Conclusion: Total ADL and instrumental ADL are associated with cognitive functions, including executive function. No significant association between examined physical performance parameters and ADL functions was observed, and consequently does not support an impact of physical function on ADL functions in patients with mild-to-moderate Alzheimer's disease and relatively well-preserved physical function. Strategies aimed to improve cognition may be better suited to improve ADL function in patients with mild-to-moderate Alzheimer's disease., Trial Registration: NCT01681602 . Registered 10 September 2012, retrospectively registered.

Cholinergic dysfunction is central in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The electroencephalography-based acetylcholine index (EEG-Ach index) has been proposed as a biomarker of cholinergic dysfunction. However, it is unclear how the EEG-Ach index relates to amyloid-beta pathology and neurodegeneration. We investigated the association between the EEG-Ach index and cerebrospinal fluid (CSF) amyloid-beta, CSF total tau, cortical thickness, and hippocampal volume from magnetic resonance imaging (MRI), and cognition. A total of 127 patients with different neurodegenerative diseases were studied. The EEG-Ach index was calculated from quantitative EEG using statistical pattern recognition. The EEG-Ach index was associated with hippocampal volume and cortical thickness in frontal, temporal, and occipital cortices. Cross-sectional sub-analyses based on a small sample suggests that the EEG-Ach index increases the closest to AD dementia, downstream to amyloid-beta pathology, CSF total tau, and hippocampal volume. We conclude that cholinergic dysfunction correlates with atrophy in brain areas important for AD pathogenesis, and this association is more prominent in the dementia stage. These results together with previous studies from this project suggest that the EEG-Ach index may be a useful biomarker for cholinergic dysfunction, with value for differential diagnosis of dementia and monitoring patients at the dementia stage., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Large-scale brain networks are disrupted in the early stages of Alzheimer's disease (AD). Electroencephalography microstate analysis, a promising method for studying brain networks, parses EEG signals into topographies representing discrete, sequential network activations. Prior studies indicate that patients with AD show a pattern of global microstate disorganization. We investigated whether any specific microstate changes could be found in patients with AD and mild cognitive impairment (MCI) compared to healthy controls (HC)., Materials and Methods: Standard EEGs were obtained from 135 HC, 117 patients with MCI, and 117 patients with AD from six Nordic memory clinics. We parsed the data into four archetypal microstates., Results: There was significantly increased duration, occurrence, and coverage of microstate A in patients with AD and MCI compared to HC. When looking at microstates in specific frequency bands, we found that microstate A was affected in delta (1-4 Hz), theta (4-8 Hz), and beta (13-30 Hz), while microstate D was affected only in the delta and theta bands. Microstate features were able to separate HC from AD with an accuracy of 69.8% and HC from MCI with an accuracy of 58.7%., Conclusions: Further studies are needed to evaluate whether microstates represent a valuable disease classifier. Overall, patients with AD and MCI, as compared to HC, show specific microstate alterations, which are limited to specific frequency bands. These alterations suggest disruption of large-scale cortical networks in AD and MCI, which may be limited to specific frequency bands., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, LLC.)

Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise ( n = 90) or treatment as usual ( n = 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD., (Copyright © 2020 Jensen, Musaeus, Frikke-Schmidt, Andersen, Beyer, Gottrup, Høgh, Vestergaard, Wermuth, Frederiksen, Waldemar, Hasselbalch and Simonsen.)

Valid diagnosis of dementia with Lewy bodies (DLB) is essential to establish appropriate treatment and care. However, the diagnostic accuracy is complicated by clinical and pathological overlap with Alzheimer's disease (AD). Cingulate island sign (CIS), defined as sparing of posterior cingulate cortex (PCC) relative to precuneus and cuneus on 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET), is included in the revised diagnostic DLB criteria. There are no guidelines for the visual grading of CIS, although visual rating is a fast-applicable method in a clinical setting. The objective was to develop a robust visual CIS scale and evaluate the performance in differentiating DLB with and without amyloid beta pathology (Aβ+/-), and AD. 18F-FDG-PET scans from 35 DLB patients, 36 AD patients, and 23 healthy controls were rated according to a visual CIS scale based on specific reading criteria. The visual CIS scale was validated against a quantitative CIS ratio derived from a region of interest analysis of PCC, precuneus, and cuneus. DLB patients had a significantly higher visual CIS score compared to AD patients, and controls. A cut-off visual CIS score of 4 significantly differentiated DLB Aβ- patients from DLB Aβ+ patients. In conclusion, the visual CIS scale is clinically useful to differentiate DLB from AD. The degree of CIS may be related to Aβ pathology in DLB patients., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

This case report describes the diagnostic approach to an 18-year-old woman, known with Asperger's syndrome (AS). She presented with abdominal pain, weight loss, nausea and a loss of appetite. Ultrasound and magnetic resonance imaging showed polycystic kidney disease (PKD) and agenesis of the dorsal pancreas (DPA). Genetic testing revealed a 1.5 mega-base deletion at chromosome 17q12, which included the HNF1β. She was diagnosed with 17q12 microdeletion syndrome, which could explain the presence of both DPA, PKD and AS.

Objective: Quantitative EEG power has not been as effective in discriminating between healthy aging and Alzheimer's disease as conventional biomarkers. But EEG coherence has shown promising results in small samples. The overall aim was to evaluate if EEG connectivity markers can discriminate between Alzheimer's disease, mild cognitive impairment, and healthy aging and to explore the early underlying changes in coherence., Methods: EEGs were included in the analysis from 135 healthy controls, 117 patients with mild cognitive impairment, and 117 patients with Alzheimer's disease from six Nordic memory clinics. Principal component analysis was performed before multinomial regression., Results: We found classification accuracies of above 95% based on coherence, imaginary part of coherence, and the weighted phase-lag index. The most prominent changes in coherence were decreased alpha coherence in Alzheimer's disease, which was correlated to the scores of the 10-word test in the Consortium to Establish a Registry for Alzheimer's Disease battery., Conclusions: The diagnostic accuracies for EEG connectivity measures are higher than findings from studies investigating EEG power and conventional Alzheimer's disease biomarkers. Furthermore, decreased alpha coherence is one of the earliest changes in Alzheimer's disease and associated with memory function., Significance: EEG connectivity measures may be useful supplementary diagnostic classifiers., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: Animal models of Alzheimer's disease show that exercise may modify β-amyloid (Aβ) deposition. We examined the effect of a 16-week exercise intervention on cortical Aβ in patients with mild-to-moderate Alzheimer's disease., Methods: Thirty-six patients with Alzheimer's disease were randomized to either one hour of aerobic exercise three times weekly for 16 weeks or usual care. Pre and post intervention, 11Carbon-Pittsburgh compound B positron emission tomography was carried out to assess cortical Aβ, and quantified using standardized uptake value rations (SUVRs)., Results: The intervention showed no effect on follow-up SUVRs in a covariance analysis with group allocation, baseline intervention SUVR, age, sex, and baseline Mini-Mental State Examination as predictors. Change in SUVRs did not correlate with changes in measures of physical or aerobic fitness., Discussion: The present findings do not support an effect of exercise on Aβ. However, the relatively short intervention period may account for a lack of efficacy. Further studies should test earlier and longer interventions.

Background: In clinical practice, it is often difficult to predict which patients with cognitive complaints or impairment will progress or remain stable. We assessed the impact of using a clinical decision support system, the PredictND tool, to predict progression in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in memory clinics., Methods: In this prospective multicenter study, we included 429 patients with SCD (n = 230) and MCI (n = 199) (female 54%, age 67 ± 9, MMSE 28 ± 2) and followed them for at least 12 months. Based on all available patient baseline data (demographics, cognitive tests, cerebrospinal fluid biomarkers, and MRI), the PredictND tool provides a comprehensive overview of the data and a classification defining the likelihood of progression. At baseline, a clinician defined an expected follow-up diagnosis and estimated the level of confidence in their prediction using a visual analogue scale (VAS, 0-100%), first without and subsequently with the PredictND tool. As outcome measure, we defined clinical progression as progression from SCD to MCI or dementia, and from MCI to dementia. Correspondence between the expected and the actual clinical progression at follow-up defined the prognostic accuracy., Results: After a mean follow-up time of 1.7 ± 0.4 years, 21 (9%) SCD and 63 (32%) MCI had progressed. When using the PredictND tool, the overall prognostic accuracy was unaffected (0.4%, 95%CI - 3.0%; + 3.9%; p = 0.79). However, restricting the analysis to patients with more certain classifications (n = 203), we found an increase of 3% in the accuracy (95%CI - 0.6%; + 6.5%; p = 0.11). Furthermore, for this subgroup, the tool alone showed a statistically significant increase in the prognostic accuracy compared to the evaluation without tool (6.4%, 95%CI 2.1%; 10.7%; p = 0.004). Specifically, the negative predictive value was high. Moreover, confidence in the prediction increased significantly (∆VAS = 4%, p < .0001)., Conclusions: Adding the PredictND tool to the clinical evaluation increased clinicians' confidence. Furthermore, the results indicate that the tool has the potential to improve prediction of progression for patients with more certain classifications.

Background: Determining the underlying etiology of dementia can be challenging. Computer- based Clinical Decision Support Systems (CDSS) have the potential to provide an objective comparison of data and assist clinicians., Objectives: To assess the diagnostic impact of a CDSS, the PredictND tool, for differential diagnosis of dementia in memory clinics., Methods: In this prospective multicenter study, we recruited 779 patients with either subjective cognitive decline (n=252), mild cognitive impairment (n=219) or any type of dementia (n=274) and followed them for minimum 12 months. Based on all available patient baseline data (demographics, neuropsychological tests, cerebrospinal fluid biomarkers, and MRI visual and computed ratings), the PredictND tool provides a comprehensive overview and analysis of the data with a likelihood index for five diagnostic groups; Alzheimer´s disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and subjective cognitive decline. At baseline, a clinician defined an etiological diagnosis and confidence in the diagnosis, first without and subsequently with the PredictND tool. The follow-up diagnosis was used as the reference diagnosis., Results: In total, 747 patients completed the follow-up visits (53% female, 69±10 years). The etiological diagnosis changed in 13% of all cases when using the PredictND tool, but the diagnostic accuracy did not change significantly. Confidence in the diagnosis, measured by a visual analogue scale (VAS, 0-100%) increased (ΔVAS=3.0%, p<0.0001), especially in correctly changed diagnoses (ΔVAS=7.2%, p=0.0011)., Conclusion: Adding the PredictND tool to the diagnostic evaluation affected the diagnosis and increased clinicians' confidence in the diagnosis indicating that CDSSs could aid clinicians in the differential diagnosis of dementia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated., Methods: It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated., Results: Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found., Conclusion: The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD.

Introduction: Brain imaging studies in healthy elderly subjects suggest a positive effect of aerobic exercise on both brain structure and function, while the effects of aerobic exercise in Alzheimer's Disease (AD) has been scarcely investigated. Methods: In a single-blinded randomized MRI study, we assessed the effects of an aerobic exercise intervention on brain volume as measured by magnetic resonance imaging (MRI) and its correlation to cognitive functioning in patients with AD. The study was a sub-study of a larger randomized controlled trial (ADEX study). Forty-one patients were assigned to a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All participants underwent whole-brain MRI at 3 Tesla and cognitive assessment at baseline and after 16 weeks. Attendance and intensity were monitored providing a total exercise load. Changes in regional brain volumes and cortical thickness were analyzed using Freesurfer software. Results: There was no effect of the type of intervention on MRI-derived brain volumes. In the entire group with and without training, Exercise load showed a positive correlation with changes in volume in the hippocampus, as well as frontal cortical thickness. Volume changes in frontal cortical thickness correlated with changes in measures of mental speed and attention and exercise load in the exercise group. Conclusion: We did not find evidence to support an effect of 16 weeks of aerobic exercise on brain volume changes in patients with AD. Longer intervention periods may be needed to affect brain structure as measured with volumetric MRI. Clinical Trial registration: ClinicalTrials.gov Identifier: NCT01681602, registered September 10th, 2012 (Retrospectively registered).

Background: Quantitative EEG (qEEG) power could potentially be used as a diagnostic tool for Alzheimer's disease (AD) and may further our understanding of the pathophysiology. However, the early qEEG power changes of AD are not well understood., Objective: To investigate the early changes in qEEG power and the possible correlation with memory function and cerebrospinal fluid biomarkers. In addition, whether qEEG power could discriminate between AD, mild cognitive impairment (MCI), and older healthy controls (HC) at the individual level., Methods: Standard EEGs from 138 HC, 117 MCI, and 117 AD patients were included from six Nordic memory clinics. All EEGs were recorded consecutively before the diagnosis and were not used for the consensus diagnosis. Absolute and relative power was calculated for both eyes closed and open condition., Results: At group level using relative power, we found significant increases globally in the theta band and decreases in high frequency power in the temporal regions for eyes closed for AD and, to a lesser extent, for MCI compared to HC. Relative theta power was significantly correlated with multiple neuropsychological measures and had the largest correlation coefficient with total tau. At the individual level, the classification rate for AD and HC was 72.9% for relative power with eyes closed., Conclusion: Our findings suggest that the increase in relative theta power may be the first change in patients with dementia due to AD. At the individual level, we found a moderate classification rate for AD and HC when using EEGs alone.

Introduction: Knowledge about the feasibility and effects of exercise programs to persons with Alzheimer's disease is lacking. This study investigated the effect of aerobic exercise on physical performance in community-dwelling persons with mild Alzheimer's disease., Methods: The single blinded multi-center RCT (ADEX) included 200 patients, median age 71 yrs (50-89). The intervention group received supervised moderate-to-high intensity aerobic exercise 1 hour × 3/week for 16 weeks. Assessments included cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy., Results: Significant between-group differences in change from baseline (mean [95%CI]) favored the intervention group for cardiorespiratory fitness (4.0 [2.3-5.8] ml/kg/min, P <0.0001) and exercise self-efficacy (1.7 [0.5-2.8] points, P =0.004). Furthermore, an exercise attendance of ≥66.6% resulted in significant positive effects on single-task physical performance and dual-task performance., Discussion: Aerobic exercise has the potential to improve cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy in community-dwelling patients with mild Alzheimer's disease., (Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline., Methods: The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales' relation to depressive symptoms, age, and cognitive status., Results: SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms., Conclusions: Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

Background: Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent., Objective: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD., Methods: In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms., Results: The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition., Conclusions: This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

Background/aims: Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers., Methods: A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex., Results: qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes., Conclusion: Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers., (© 2016 S. Karger AG, Basel.)

Background: Affective-motivational and sensory-discriminative aspects of pain were investigated in patients with mild to moderate Alzheimer disease (AD) and healthy elderly controls using the cold pressor test tolerance and repetitive stimuli of warmth and heat stimuli, evaluating the stimulus-response function., Methods: A case-control design was applied examining 33 patients with mild to moderate AD dementia and 32 healthy controls with the cold pressor test (4°C). Warmth detection threshold (WDT) and heat pain threshold (HPT) were assessed using 5 stimulations. A stimulus-response function was estimated using 4 incrementally increasing suprathreshold heat stimuli., Results: Cold pressor tolerance was lower in patients with AD dementia than in controls (p = 0.027). There were no significant differences between groups regarding WDT and HPT. Significant successive increases in HPT assessments indicated habituation (p < 0.0001), which was similar in the 2 groups (p = 0.85). A mixed model for repeated measures demonstrated that pain rating of suprathreshold stimuli depended on HPT (p = 0.0004) and stimulus intensity (p < 0.0001). Patients with AD dementia had significantly lower increases in pain ratings than controls during suprathreshold stimulation (p = 0.0072)., Conclusion: Our results indicate that AD dementia is not associated with a propensity toward development of sensitization or a lack of habituation, suggesting preservation of sensory-discriminative aspects of pain perception. The results further suggest that the attenuated cold pressor pain tolerance may relate to impairment of coping abilities. Paradoxically, we found an attenuated stimulus-response function, compared to controls, suggesting that AD dementia interferes with pain ratings over time, most likely due to memory impairment., (© 2015 American Academy of Neurology.)

Background: Autonomic function has received little attention in Alzheimer's disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function., Objective: To investigate autonomic function using standardized techniques in patients with AD and healthy age-matched controls., Method: Thirty-three patients with mild to moderate AD and 30 age- and gender-matched healthy controls, without symptoms of autonomic dysfunction, underwent standardized autonomic testing with deep breathing, Valsalva maneuver, head-up tilt, and isometric handgrip test. Brachial pressure curve and electrocardiogram were recorded for off-line analysis of blood pressure and beat-to-beat heart rate (HR)., Results: AD patients had impaired blood pressure responses to Vasalva maneuver (p < 0.0001) and HR response to isometric contraction (p = 0.0001). A modified composite autonomic scoring scale showed greater degree of autonomic impairment in patients compared to controls (patient: 2.1 ± 1.6; controls: 0.9 ± 1.1, p = 0.001). HR response to deep breathing and Valsalva ratio were similar in the two groups., Conclusion: We identified autonomic impairment ranging from mild to severe in patients with mild to moderate AD, who did not report autonomic symptoms. Autonomic impairment was mainly related to impairment of sympathetic function and evident by impaired blood pressure response to the Vasalva maneuver. The clinical implications of this finding are that AD may be associated with autonomic disturbances, but patients with AD may rarely report symptoms of autonomic dysfunction. Future research should systematically evaluate symptoms of autonomic function and characterize risk factors associated with autonomic dysfunction.

Background: Establishing a diagnosis of dementia in young patients may be complex and have significant implications for the patient. The aim of this study was to evaluate the quality of the diagnostic work-up in young patients diagnosed with dementia in the clinical routine., Methods: Two hundred patients were randomly selected from 891 patients aged ≤65 years registered with a diagnosis of dementia for the first time in 2008 in Danish hospitals, and 159 medical records were available for review. Three raters evaluated their medical records for the completeness of the diagnostic work-up on which the diagnosis of dementia had been based, using evidence-based guidelines for the diagnostic evaluation of dementia as reference standards., Results: According to the rater review, only 111 (70%) patients met the clinical criteria for dementia. An acceptable diagnostic work-up including all items of recommended basic diagnostic evaluation was performed in only 24%, although more often (28%) in the subgroup of patients where dementia was confirmed by raters., Conclusion: This first nationwide study of unselected young patients registered with a diagnosis of dementia indicated that the concept of dementia may be misinterpreted by clinicians and that a diagnosis of dementia in the young is only rarely based on a complete basic diagnostic work-up, calling for increased competency.

Aims: To evaluate the efficacy of acupuncture, and sweeping of the fetal membranes, as methods for induction of labor., Methods: Four hundred and seven pregnant women with normal singleton pregnancies and cephalic presentations were randomized at three delivery wards in Denmark at day 290 of gestation into groups of acupuncture, sweeping, acupuncture and sweeping and controls. The primary objective was to compare the proportion of women going into labor before induction of labor at 294 days in the four groups. The secondary objective was to compare the combined groups: with and without acupuncture, and with and without sweeping of the fetal membranes. The midwives, completing the forms for the trial at labor or induction, were blinded to group assessments., Results: Four hundred and seventeen women were randomized. Ten were excluded after randomization. One hundred and four women were randomized to acupuncture, 103 to sweeping of the membranes, 100 to both acupuncture and sweeping, and 100 were randomized to the control group. Comparison of the four groups demonstrated no significant difference in the number of women achieving spontaneous labor before planned induction. No difference was demonstrated by comparing the combined groups treated with acupuncture with the groups not treated with acupuncture (P=0.76). However, significantly more women went into labor before planned induction (P=0.02) in the combined groups receiving sweeping, compared with the groups not treated with sweeping., Conclusions: Acupuncture at 41+ weeks of gestation did not reduce the need for induction. The study was of a sufficient size to demonstrate, in parallel, that sweeping of the fetal membranes significantly reduced the need of induction, sparing about 15% for formal induction of labor.

Unlabelled: Patients who have dementia with Lewy bodies (DLB) show both clinical and histopathologic overlap with Alzheimer disease patients and Parkinson disease patients. In this study, we correlated the core features of DLB (dementia, parkinsonism, hallucinations, and fluctuations) with striatal dopamine transporter (DAT) availability as assessed with SPECT and (123)I-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane ((123)I-PE2I) in patients with newly diagnosed DLB., Methods: Two hundred eighty-eight patients were consecutively included in the study as they were referred for diagnostic SPECT scanning of DAT with (123)I-PE2I. Of those patients, 51 had, on the basis of clinical guideline criteria, a probable-DLB diagnosis at follow-up 16 ± 11.6 mo later. Before or on the day of the SPECT scan, DLB patients had a routine neurologic examination including Hoehn and Yahr grading and were cognitively evaluated with the Mini Mental State Examination., Results: There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT., Conclusion: In patients with newly diagnosed DLB, symptoms are not associated with a reduction in striatal DAT despite its firm involvement in DLB pathology.

Background/aims: The Rowland Universal Dementia Assessment Scale (RUDAS) is a brief cognitive screening test that was developed to detect dementia in multicultural populations. The RUDAS has not previously been validated in multicultural populations outside of Australia. The aim of this study was to evaluate the diagnostic accuracy of the RUDAS in a multicultural sample of patients referred to Danish memory clinics., Methods: Data were collected from 137 consecutive patients (34 with an immigrant background) in three Danish memory clinics. All patients were given the RUDAS as a supplement to the standard diagnostic workup., Results: Diagnostic accuracy for the RUDAS [area under the curve (AUC) = 0.838] was similar to that of the Mini-Mental State Examination (MMSE; AUC = 0.840). The cutoff score with the best balance of sensitivity, specificity and accuracy was <24/30 for the RUDAS (sensitivity 0.69, specificity 0.80) and <25/30 for the MMSE (sensitivity 0.76, specificity 0.83). In contrast to the MMSE, regression analyses revealed that the RUDAS was unaffected by factors related to the patients' immigrant backgrounds., Conclusion: The RUDAS showed high specificity and proved to be less affected by cultural and linguistic factors than the MMSE, making it a particularly valuable tool when screening for cognitive impairment in elderly multicultural patient populations., (© 2013 S. Karger AG, Basel.)

Purpose: To examine the diagnostic sensitivity and specificity of dopamine transporter SPECT imaging with a highly dopamine transporter selective radioligand. The study included consecutively enrolled, drug-naive patients with an average short history of parkinsonian motor symptoms, referred for diagnostic scanning., Methods: The study group comprised 288 patients naive to antiparkinson treatment who were enrolled as they were admitted for a diagnostic SPECT scan with the radioligand [(123)I]-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl)nortropane ((123)I-PE2I). After the diagnostic scanning, patients were followed clinically with an average follow-up of 19.7 ± 12.5 months., Results: A diagnosis could be clinically settled in 189 patients and among these patients, a dopamine transporter scan had a sensitivity of 88% and a specificity of 91% for discrimination between patients with and without striatal neurodegeneration. In cognitively impaired patients (Mini Mental State Examination <27) the specificity was 75% and the sensitivity 95%. A striatal anterior-posterior ratio (APR) of >2 differentiated between idiopathic Parkinson's disease and atypical parkinsonian syndromes with a specificity of 84% and a sensitivity of 63%., Conclusion: In drug-naive patients with subtle clinical parkinsonian motor symptoms, dopamine transporter scan using (123)I-PE21 has a high sensitivity and specificity in distinguishing between patients with and without striatal neurodegeneration. The specificity is lower in patients who are also cognitively impaired. Calculation of the striatal APR can assist in differentiating between idiopathic Parkinson's disease and atypical parkinsonian syndromes.

Background: Little is known about the quality of the diagnostic evaluation and the validity of dementia diagnoses in young patients established in routine clinical practice. The aim of this study was to investigate the validity of the diagnosis of dementia registered in the Danish nationwide hospital registers in young patients., Methods: Two hundred patients were randomly selected from 891 patients <65 years registered with a dementia diagnosis for the first time in 2008. The patients' medical records were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and current clinical criteria for specific dementia subtypes., Results: A registered diagnosis was found to be correct in only 59%. A misdiagnosis of dementia occurred primarily in patients with depression or alcohol abuse., Conclusion: Our results suggest that dementia is overregistered and overdiagnosed in young patients. This may be due to a different symptom profile of dementia in young patients, lack of knowledge among clinical physicians and the wide range of conditions which may be misinterpreted as dementia., (Copyright © 2012 S. Karger AG, Basel.)

Nonquantitative studies indicate that the cerebellum is neuropathologically affected in Alzheimer's disease; however, no quantitative studies on the subject have yet been conducted. Ten cerebella from elderly female subjects with severe Alzheimer's disease and 10 age- and gender-matched controls were examined. The cerebellum was divided into 5 regions and the Purkinje and granule cell number and density, cortical volume, molecular and granular layer volume and thickness, white matter volume, surface area, and the Purkinje cell gradient were stereologically estimated. There was no significant difference between the groups in Purkinje or granule cell number or density, and no overall difference in Purkinje cell gradient. However, there was a significant 12.7% reduction in total cerebellar volume in the Alzheimer's group and significant localized differences between the groups regarding other parameters. The relative lack of neuropathological changes in the cerebellum of severely demented Alzheimer's patients suggests that neuronal cell bodies on a global scale apparently still are intact., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background/aims: Diagnostic evaluation of dementia for ethnic minority patients may be challenging. This study aimed to evaluate the quality of diagnostic evaluation of dementia for patients from ethnic minorities in Denmark., Methods: The Danish national hospital registers were used to identify patients from the main ethnic minority groups in Denmark, who were diagnosed with dementia in the period 2005-2007. Three raters independently reviewed the patients' medical records. Data were compared to data from a previous similar study in the general Danish population., Results: Fifty-seven medical records were reviewed. An acceptable diagnostic workup was documented in only 23% of the patients. Dementia diagnosis was confirmed in 35%. Significant differences in the quality of the diagnostic evaluation were found between patients from ethnic minorities and the general population., Conclusion: There are significant ethnic disparities in the quality of diagnostic evaluations and outcome of dementia in the secondary healthcare sector., (Copyright © 2011 S. Karger AG, Basel.)

Introduction: We investigated non-attendance and cancellation of appointment on the day of the appointment in private psychiatric practice in Denmark., Material and Methods: Data from 2005 from a quality assurance database for private psychiatric practice (QAD3P) and a pilot investigation during one week comprise the data basis for this study. A total of 14 psychiatrists, i.e. approximately 10% of the private practising psychiatrists, reported to the database in 2005 and 16 psychiatrists reported to the pilot investigation. Non-attendance at the first consultation was not recorded., Results: Patients missed 6,7% of the appointments. A total of 22,8% of patients missed a minimum of one appointment. There was no difference between the sexes. Non-attendance was more common among younger patients than among elderly patients. Especially patients with eating disorders and emotionally unstable personality disorder had many missed appointments. Psychiatrists in regions with few psychiatrists had more non-attendances among their patients than psychiatrist in regions with more psychiatrists. There were more non-attendances in treatments that ended by non-attendance than in treatments with agreed termination. The pilot study saw 17 non-attendances and 23 cancelled appointments, and among these the psychiatrists found that the reasons for cancelling were reasonable in 17 cases., Conclusion: Non-attendance and late cancellation of appointments at Danish private psychiatric practice amounted to 6.7%. This occurs in all groups of patients and to all psychiatrists.

Background: Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia., Methods: CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression., Results: No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not., Conclusions: Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias.

Objective: This study examined diagnoses of patients treated by psychiatrists in private practice in Denmark and identified predictors of dropout., Methods: Between 1996 and 2006, a total of 37 psychiatrists contributed data about treatment episodes to a quality assurance database. The diagnostic distribution was determined, and univariate and backward stepwise regression analysis was used to identify dropout predictors., Results: Among 41,462 episodes (35,205 patients), 39%-41% were for an ICD-10 diagnosis of affective disorders, 30%-35% for nervous and stress-related disorders, and 10% for personality disorders. For episodes involving these diagnoses, 26,443 were terminated; 26.2% ended in dropout, which was predicted by the patient's being male, younger age (< or =44 years), presence of personality disorder, shorter treatment duration (< or =111 days), use of psychotropic medication, and a larger population per psychiatrist in the catchment area., Conclusions: Attention should be given to younger male patients treated for personality disorders, because they are at higher risk of treatment dropout.

Background: The authors conducted a study to determine one-year coronal and root caries increments in patients newly diagnosed as having Alzheimer disease (AD), other dementia (OD) or no dementia., Methods: The authors recruited patients from two hospital memory clinics in Copenhagen. The oral examination included an assessment of dental status and dental caries. The authors used a structured questionnaire to obtain information regarding demographic, social and functional variables., Results: In the baseline study, 106 dentate patients participated. Of these, 77 completed the follow-up study. The participants' mean age was 81.9 years at baseline and 82.5 years at follow-up. At baseline, 87 (82 percent) of 106 participants had dementia and at follow-up, 64 (83 percent) of 77 participants had dementia. The mean number of decayed tooth surfaces was significantly higher at follow-up than at baseline for all participants, and the number was highest for the OD group. The one-year adjusted caries and filling increments (ADJCIs) were high for participants with and without dementia but were highest for participants in the AD and OD groups. Baseline risk factors for developing elevated coronal and root ADJCIs included having caries, having many teeth and being older than 80 years., Conclusions: Elderly people referred to a memory clinic were at an elevated risk of developing high levels of coronal and root-surface caries during the first year after referral, and those with a dementia diagnosis other than AD appeared to be at a particularly high risk of developing multiple carious lesions during the first year after diagnosis., Clinical Implications: These findings underscore the importance of addressing the oral health needs of elderly people suspected of having experienced cognitive decline.

Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD). The underlying neurobiological mechanism of DLB is not fully understood and no generally accepted biomarkers are yet available for the diagnosis of DLB. In a recent MRI study, DLB patients displayed hypothalamic atrophy whereas this region was not affected in AD patients. Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed selectively in neurons in the hypothalamus. Here, we found that CSF CART levels were significantly reduced by 30% in DLB patients (n = 12) compared to controls (n = 12) as well as to AD patients (n = 14) using radioimmunoassay. Our preliminary results suggest that reduced CSF CART is a sign of hypothalamic dysfunction in DLB and that it may serve as a biomarker for this patient group.

Background: We conducted a nationwide registry-based study of the quality of diagnostic evaluation for dementia in the secondary health care sector., Method: Two hundred patients were randomly selected from the patient population (4,682 patients) registered for the first time with a dementia diagnosis in the nationwide hospital registries during the last 6 months of 2003. Through medical record review, we evaluated the completeness of the work-up on which the dementia diagnosis was based, using evidence-based dementia guidelines as reference standards., Results: Satisfactory or acceptable completion of the basic dementia work-up was documented in 51.3% of the patients. Only 11.5% of those with unsatisfactory work-up were referred to follow-up investigations. Dementia syndrome was confirmed in 88.5% of the cases, but correct subtypes were diagnosed in only 35.1%., Conclusion: The adherence to clinical guidelines concerning dementia work-up is inadequate in the secondary health care sector. Our findings call for improvement in the organization of clinical dementia care, for education of specialists and for changes in attitude towards making a diagnosis of dementia.

Background: Mutations in the Presenilin 2 gene (PSEN2) are rare causes of Alzheimer's disease (AD). Pathogenic mutations in the genes associated with autosomal dominant inherited AD have been shown to alter processing of the amyloid precursor protein (APP) resulting in a relative increase of the amount of Abeta42 peptide., Methods and Results: We present a patient with neuropathologically confirmed early-onset AD characterized by profound language impairment. The patient was heterozygous for a novel missense mutation in exon 11 of the PSEN2 gene leading to a predicted amino acid substitution from valine to methionine in position 393, a conserved residue. However, in vitro expression of PSEN2 V393M cDNA did not result in detectable increase of the secreted Abeta42/40 peptide ratio. The mutation was not found in 384 control individuals tested., Conclusions: The possible pathogenic nature of the mutation is not clarified. We discuss the limitations of functional PSEN2 studies and the challenges associated with genetic counselling of family members at risk.

An interlaboratory study was conducted to determine the performance characteristics of a new method for the determination of phytase activity in feed samples. The method is based on the principle that inorganic phosphate is released from the substrate phytate under defined assay conditions and has been validated for its suitability to measure the enzyme activity of various phytase products. Two different experimental designs of the study were applied, allowing for the estimation of the precision of the method under repeatability, intermediate precision and reproducibility conditions, respectively. The relative standard deviation for repeatability (RSDr) ranged from 2.2 to 10.6% and the RSD for reproducibility (RSDR) ranged from 5.4 to 15%. The suitability of the validated method for the intended purpose was demonstrated. The obtained performance profile of the method validated in this study was comparable to that of similar methods that were exclusively validated for one phytase product.

Objectives: To examine the prevalence of coronal and root caries in a memory clinic-based population of elderly patients with and without a diagnosis of dementia and to examine the influence of age, sex, social relations, social position, and functional ability., Design: Cross-sectional., Setting: Patients referred with possible cognitive dysfunction were recruited from two university hospital dementia clinics., Participants: In total, 106 dentate persons participated in the study. Mean age was 82, 69 were women, and 87 had a diagnosis of dementia., Measurements: Data from interviews and a clinical examination were collected. The diagnosis of dementia was made at the dementia clinics according to the criteria of International Classification of Diseases, Tenth Revision. Active coronal and root caries was assessed using previously defined diagnostic criteria from the National Institute of Dental and Craniofacial Research., Results: The mean number of coronal and root surfaces with caries was statistically significantly higher in subjects with a diagnosis of dementia (7.0 vs 2.7, P<.05). Subjects with a diagnosis of Alzheimer's disease had a significantly higher mean number of root surfaces with caries (4.9, P<.05) than subjects with other dementia diagnoses (2.3) and those without dementia (1.7). People with Alzheimer's disease also had significantly more mean total caries than subjects without dementia (7.8 vs 2.7, P<.05). Participants with a Mini-Mental State Examination (MMSE) score less than 24 had significantly more caries than participants with a MMSE-score of 24 or higher (7.6 vs 4.3, P<.05)., Conclusion: Patients with newly diagnosed dementia already had a high level of active dental caries when they were referred to the memory clinic. The high caries prevalence was related to dementia type and severity.

Background: The validity of dementia diagnoses in the Danish nationwide hospital registers was evaluated to determine the value of these registers in epidemiological research about dementia., Methods: Two hundred patients were randomly selected from 4,682 patients registered for the first time with a dementia diagnosis in the last 6 months of 2003. The patients' medical journals were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and specific dementia subtypes. The patients who were still alive in 2006 were invited to an interview., Results: One hundred and ninety-seven journals were available for review and 51 patients were interviewed. A registered diagnosis of dementia was found to be correct in 169 (85.8%) cases. Regarding dementia subtypes, the degree of agreement between the registers and the results of the validating process was low with a kappa of 0.36 (95% CI 0.24-0.48)., Conclusion: The validity of dementia syndrome in the Danish hospital registers was high and allows for epidemiological studies about dementia. Alzheimer's disease, although underregistered, also had a good validity once the diagnosis was registered. In general, other ICD-10 dementia subtypes in the registers had a low validity and are less suitable for epidemiological research., (2007 S. Karger AG, Basel)