[Recommendations for the prevention, diagnosis, and therapy of addiction in the elderly]. / Recommandations pour la prévention, le diagnostic et la thérapie des addictions à l'âge avancé.

In old age, the chronic use of substances such as alcohol and sedatives, and more recently opioids, is a major public health and personal problem. Despite this, relatively little attention has been paid to the disorders associated with the use of these substances. These recommendations have been formulated by the Swiss Society for Elderly Psychiatry and Psychotherapy (SPPA) in collaboration with the Swiss Nurses' Association (SNA) and the Swiss Society for Addiction Medicine (SSAM). They provide a summary of the knowledge about addiction disorders in old age for the benefit of those working with patients, with the aim of strengthening prevention, early detection and appropriate interventions.

À l'âge avancé, la consommation chronique de substances comme l'alcool et les sédatifs, et plus récemment les opioïdes, représente un important problème pour les personnes concernées et de santé publique. Malgré cela, relativement peu d'attention a été accordée aux troubles associés à la consommation de ces substances. Les présentes recommandations ont été formulées par la Société suisse de psychiatrie et psychothérapie de la personne âgée (SPPA) en collaboration avec l'Association suisse des infirmières et infirmiers (ASI) et la Société suisse de médecine de l'addiction (SSMA). Elles mettent à la disposition des intervenants auprès des patients un résumé des connaissances au sujet des troubles addictifs à l'âge avancé, avec comme objectif de renforcer la prévention et le dépistage précoce, et des interventions adaptées.

A qualitative study to investigate Swiss hospital personnel's perceived importance of and experiences with patient's mental-somatic multimorbidities.

BACKGROUND: Mental-somatic multimorbidity in general hospital settings is associated with long hospital stays, frequent rehospitalization, and a deterioration of disease course, thus, highlighting the need for treating hospital patients more holistically. However, there are several challenges to overcome to address mental health conditions in these settings. This study investigated hospital personnel's perceived importance of and experiences with mental-somatic multimorbidities of patients in hospital settings in Basel, Switzerland, with special consideration of the differences between physicians and nurses. METHODS: Eighteen semi-structured interviews were conducted with nurses (n = 10) and physicians (n = 8) in different hospitals located in Basel, Switzerland. An inductive approach of the framework analysis was used to develop the themes. RESULTS: Four themes emerged from the data analysis: 1) the relevance of mental-somatic multimorbidity within general hospitals, 2) health professionals managing their emotions towards mental health, 3) knowledge and competencies in treating patients with mental-somatic multimorbidity, and 4) interprofessional collaboration for handling mental-somatic multimorbidity in hospital settings.The mental-somatic multimorbidities in general hospital patients was found to be relevant among all hospital professionals, although the priority of mental health was higher for nurses than for physicians. This might have resulted from different working environments or in efficient interprofessional collaboration in general hospitals. Physicians and nurses both highlighted the difficulties of dealing with stigma, a lack of knowledge of mental disorders, the emphasis place on treating somatic disorders, and competing priorities and work availability, which all hindered the adequate handling of mental-somatic multimorbidity in general hospitals. CONCLUSION: To support health professionals to integrate mental health into their work, proper environments within general hospitals are needed, such as private rooms in which to communicate with patients. In addition, changes in curriculums and continuing training are needed to improve the understanding of mental-somatic multimorbidities and reduce negative stereotypes. Similarly, interprofessional collaboration between health professionals needs to be strengthened to adequately identify and treat mentally multimorbid patients. A stronger focus should be placed on physicians to improve their competencies in considering patient mental health in their daily somatic treatment care.

Decision-making capacity evaluations: the role of neuropsychological assessment from a multidisciplinary perspective.

Decision-making capacity (DMC) in aging adults has become increasingly salient as the number of older adults, life expectancy, and the amount of wealth to be transferred from older generations have all increased. The accurate and reliable determination of older adults' DMC is a particularly important topic given its implication in legal, financial, and health decisions. Based upon the four-ability DMC model promulgated by Appelbaum and Grisso in the 1980's, a number of MacArthur Competence Assessment Tools have been developed and widely utilized. However, these tools do not include cognitive testing or other sources of objective data and have limited validity in a medico-legal setting, necessitating additional options for the evaluation of DMC. This is significant from the perspective of the patient because they have a vested interest in accurate and objective assessment of their DMC across domains.Given the disparities in the assessment of DMC, the authors propose, through this debate article, that the evaluation of DMC in the aging adult population utilize a combination of traditional interview and domain specific instruments and neuropsychological testing. To achieve a consensus on the issue, medical experts in a number of fields related to capacity evaluation, including psychiatry, neurology, neuropsychology, and general medicine were consulted and recruited as authors. Experts in Swiss law and ethics were also consulted and provided input.A tendency to focus on a single capacity, and in particular, the ability to consent to medical treatment, arose in the literature. Similarly, there are many instruments purporting to evaluate a single capacity (e.g., consenting to medical treatment, managing finances), while other areas important to the evaluation of DMC received little attention (e.g., activities of daily living, the ability to live independently, to marry, to resist undue influence, and to make a will or advanced care directive). Medical and legal experts in the multidisciplinary group agreed that there is a clear need for more consistency across evaluation of DMC domains and that a combined approach of traditional methods and neuropsychological testing provides a more thorough evaluation and better serves the patient.

[Alzheimer's disease - State of the art, and emerging diagnostics and therapeutics]. / Morbus Alzheimer ­ State of the art und Blick in die Zukunft.

Alzheimer's disease - State of the art, and emerging diagnostics and therapeutics Abstract. Alzheimer's disease (AD) constitutes the most prevalent neurodegenerative disorder, and the most frequent cause of dementia. Current diagnostics include a clinical examination, brain imaging, as well as laboratory testing in order to exclude other treatable disorders. Depending on the findings constellation a lumbar puncture with determination of amyloid-ß-, tau- and phospho-tau-proteins, PET imaging and if necessary further investigations are performed. Acetylcholineesteraseinhibitors as well as the NMDA-antagonist mematine allow symptomatic treatment of AD. The development of novel curative drugs is now showing considerable progress. After initially frustrating results, immunotherapies addressing amyloid-ß pathology are now showing first positive effects when administered early in the disease course. First immunotherapies targeting tau pathology are furthermore reaching phase 2 and 3 trials, after hints of positive clinical effects in phase 1 trials. An additional set of more than 70 trials investigates non-immune mediated treatment strategies. Diagnostic advances include the development of amyloid-PET imaging, where after the amyloid-ß-PET, tau-PET imaging is now reaching clinical implementation. In parallel to the technical advances in cerebrospinal fluid diagnostics, first blood-based biomarkers for AD are being developed.

A common challenge in older adults: Classification, overlap, and therapy of depression and dementia.

Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk. Finally, we summarize the existing evidence for both pharmacotherapy and psychotherapy of depression in demented patients. There is an urgent need for large-scale collaborative research to elucidate the role and interplay of clinical and biological features in elderly individuals with depressive disorders who are at elevated risk for developing dementia. To overcome barriers for successful drug development, we propose the introduction of the precision medicine paradigm to this research field.

Dissociation in Rating Negative Facial Emotions between Behavioral Variant Frontotemporal Dementia and Major Depressive Disorder.

OBJECTIVE: Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. DESIGN AND PARTICIPANTS: The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. MEASUREMENTS AND RESULTS: Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. CONCLUSIONS: By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD.

Comparison of Clock Test Deficits Between Elderly Patients With Early and Late Onset Depression.

To compare clock test deficits in elderly patients with early onset depression (EOD) and late onset depression (LOD), we assessed 32 elderly healthy controls (HCs), 26 patients with EOD, and 27 patients with LOD with the clock drawing test (CDT), clock setting test, clock reading test, and the Tübingen Clock Questionnaire testing semantic memory about clock times. There was no significant difference in depression severity between patients with EOD and LOD. Patients with LOD had significantly lower scores on the CDT than patients with EOD and HCs. Semantic memory impairment concerning minute hand functionality was highly correlated with CDT performance and was significantly different between the EOD and the LOD groups. It can be suggested that significant differences in cognitive impairment severity between patients with EOD and LOD can be detected with CDT. Semantic memory impairment concerning minute hand functionality might affect CDT test results in elderly patients with depression.

Functional characteristics of control adaptation in intermodal sensory processing.

The present work investigated functional characteristics of control adjustments in intermodal sensory processing. Subjects performed an interference task that involved simultaneously presented visual and auditory stimuli which were either congruent or incongruent with respect to their response mappings. In two experiments, trial-by-trial sequential congruency effects were analysed for specific conditions that allowed ruling out "non-executive" contributions of stimulus or response priming to the respective RT fluctuations. In Experiment 1, conflict adaptation was observed in an oddball condition in which interference emanates from a task-irrelevant and response-neutral low-frequency stimulus. This finding characterizes intermodal control adjustments to be based - at least partly - on increased sensory selectivity, which is able to improve performance in any kind of interference condition which shares the same or overlapping attentional requirements. In order to further specify this attentional mechanism, Experiment 2 defined analogous conflict adaptation effects in non-interference unimodal trials in which just one of the two stimulus modalities was presented. Conflict adaptation effects in unimodal trials exclusively occurred for unimodal task-switch trials but not for otherwise equivalent task repetition trials, which suggests that the observed conflict-triggered control adjustments mainly consist of increased distractor inhibition (i.e., down-regulation of task-irrelevant information), while attributing a negligible role to target amplification (i.e., enhancement of task-relevant information) in this setup. This behavioral study yields a promising operational basis for subsequent neuroimaging investigations to define brain activations and connectivities which underlie the adaptive control of attentional selection.

CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study.

INTRODUCTION: The aim of this study was to test the diagnostic value of cerebrospinal fluid (CSF) beta-amyloid (Aß1-42), phosphorylated tau, and total tau (tau) to discriminate Alzheimer's disease (AD) dementia from other forms of dementia. METHODS: A total of 675 CSF samples collected at eight memory clinics were obtained from healthy controls, AD dementia, subjective memory impairment, mild cognitive impairment, vascular dementia, Lewy body dementia (LBD), fronto-temporal dementia (FTD), depression, or other neurological diseases. RESULTS: CSF Aß1-42 showed the best diagnostic accuracy among the CSF biomarkers. At a sensitivity of 85%, the specificity to differentiate AD dementia against other diagnoses ranged from 42% (for LBD, 95% confidence interval or CI = 32-62) to 77% (for FTD, 95% CI = 62-90). DISCUSSION: CSF Aß1-42 discriminates AD dementia from FTD, but shows significant overlap with other non-AD forms of dementia, possibly reflecting the underlying mixed pathologies.

[Suicide in the elderly ­ risk factors and prevention]. / Suizid bei älteren Menschen - Risikofaktoren und Prävention.

Suicide rates are highest among the elderly in Switzerland. The estimated number of unreported cases is particularly high in this age group. The risk factors are multidimensional, including depression and social isolation. The detection and management of the controllable risk factors, foremost depression, is of particular importance for suicide prevention. Old age depression often shows an atypical presentation, is misinterpreted as a normal process of aging and is not adequately treated.

Cognitive and affective dysfunctions in autoimmune thyroiditis.

Hashimoto's thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced gray matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto's encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits.

Aging effects on the encoding/retrieval flip in associative memory: fMRI evidence from incidental contingency learning.

Introduction: Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning. Methods: We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI. Results: According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects. Discussion: In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.

Low performance in attention testing is associated with reduced grey matter density of the left inferior frontal gyrus in euthyroid patients with Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) can casually co-occur with an encephalopathy associated with autoimmune thyroid disease. Recently we found an increased occurrence of weaknesses in sustained attention and response inhibition in a subgroup of euthyroid patients with HT as obtained by the d2 attention test. Previous studies in healthy subjects and patients with brain lesions demonstrated a pivotal role for the left inferior frontal gyrus (LIFG) in these skills. Therefore, we studied the association between the performance in the d2 test and grey matter (GM) density of the LIFG in 13 euthyroid patients with HT compared to a control group of 12 euthyroid patients with other thyroid diseases. A significant correlation between GM density and d2 test total score was detected for the opercular part of the LIFG in patients with HT (p<0.001), but not in the control group (p=0.94). Regression in patients with HT was significantly stronger than in the control group (p=0.02). Moreover, GM density was significantly reduced when comparing HT patients with control patients that scored in the lower third during d2 attention testing (p<0.05). It can be concluded that in HT performance in the d2 test correlated with GM density of the LIFG. Particularly low achievement was associated with reduced GM density of this brain region suggesting an influence of autoimmune processes on the frontal cortex in this disease. This could be due to not yet known antibodies affecting brain morphology or an influence of thyroid antibodies themselves.

Recognition performance differentiates between elderly patients in the long term course of secondary progressive multiple sclerosis and amnestic mild cognitive impairment.

BACKGROUND: Cognitive impairment is a common symptom of multiple sclerosis (MS), but little is known about cognitive decline in patients in the long-term course of progressive MS. Because advancing age is the most significant risk factor for Alzheimer's Disease (AD), AD-related pathology must be considered in elderly patients with MS. Amnestic mild cognitive impairment (aMCI) represents the prodromal phase of AD with subjects showing memory impairment that does not improve with recognition testing. OBJECTIVE: We sought to identify disease-dependent deterioration patterns by comparing elderly patients with secondary progressive MS (SPMS) and with aMCI using the Consortium to Establish a Registry for Alzheimer's Disease test battery. METHODS: This study included 120 age-, education- and gender-matched participants, including healthy controls (n=40), SPMS patients (n=40), and aMCI patients (n=40). RESULTS: Episodic memory deficits appeared in the long-term course of SPMS. Deficits were associated with deterioration of executive function, but not impairment of memory storage as recognition was preserved in SPMS in contrast to the patients with aMCI. CONCLUSION: Through neuropsychological testing, MS-related episodic memory impairment due to deteriorated executive function can be distinguished from AD-related encoding and storage deficits. Hence, neuropsychological testing may help to identify AD-related pathology in SPMS patients.

The Mini-Cog, Clock Drawing Test, and the Mini-Mental State Examination in a German memory clinic: specificity of separation dementia from depression.

BACKGROUND: The aim of this study was to assess the specificities of the Mini-Cog, the Clock Drawing Test (CDT), and the Mini-Mental State Examination (MMSE) against depression and healthy controls in a German Memory Clinic. Furthermore, we analyzed the specificities of all three screening instruments in dependence of actual depression severity. METHODS: Data from 142 depressed elderly, 438 dementia patients, and 64 healthy controls were retrospectively analyzed. The CDT and an extraction of the three-item recall of the MMSE were used to constitute the Mini-Cog algorithm. Depression severity was rated by either the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) depending on the age of the patients. RESULTS: The Mini-Cog achieved a specificity of 79.6% against depressed elderly and 100.0% against healthy subjects (p < 0.001). Similarly, the specificities of the CDT (83.8%) and MMSE (92.3% at a cut-off ≤24 and 90.8% at ≤25, respectively) against healthy subjects were significantly higher than the specificities against depressed patients (each p < 0.05). Concerning the depressed patients, the MMSE demonstrated significant higher specificity than the Mini-Cog and the CDT, but also showed the lowest sensitivity for the detection of dementia. Surprisingly, the depression severity had no effect on the specificity of the Mini-Cog and the CDT, only the MMSE was susceptible for the depression severity. CONCLUSION: Although the MMSE showed higher specificities, the weighting between the sensitivities and specificities in all tests prove again the Mini-Cog as a short, valid, and sensitive screening tool.

Thyroid peroxidase antibody positivity is associated with symptomatic distress in patients with Hashimoto's thyroiditis.

Previous studies suggest impairments of physical, mental, and psychic well-being in patients with Hashimoto's thyroiditis (HT), but these impairments have been shown to be independent of thyroid dysfunction. In 64 euthyroid patients with HT, symptomatic distress was assessed with the Symptom Checklist-90-Revised (SCL-90-R), a 90-item multidimensional self-report symptom inventory using a 5-point rating scale. In a subgroup of patients, endocrine testing 3 years prior to the current investigation was available. Anti-thyroid peroxidase antibodies (TPO-Abs) were associated with the three SCL-90-R global indices Global Severity Index (GSI), Positive Symptom Distress Index (PSDI), and Positive Symptom Total (PST) as well as with somatization and obsessive-compulsive symptoms after adjustment for age, gender, and thyroid function as assessed by TSH levels (all p<0.05). HT patients positive for TPO-Abs showed poorer results in the three SCL-90-R global indices as well as in the three domains: somatization, obsessive-compulsive symptoms, and depression (all p≤0.02), though the aforementioned associations did not withstand sequential Bonferroni correction for multiple testing. In contrast, TPO-Abs positivity, defined as TPO-Abs >100 IU/l, significantly predicted poorer psychosocial well-being in all of the three SCL-90-R global indices after three years, even after correction (all p≤0.02). In conclusion, high TPO-Abs are associated with poor physical and psychological well-being and appear to predict future health perception in HT patients.

Clock test deficits related to the global cognitive state in Alzheimer's and Parkinson's disease.

BACKGROUND/AIMS: Clock drawing (CD) seems to be impaired quite early in the process of cognitive decline in Parkinson's disease (PD). METHODS: We assessed performance on the CD test (CDT), clock setting test (CST) and clock reading test (CRT) in 32 elderly healthy controls, 41 patients with PD, 23 patients with amnestic mild cognitive impairment (aMCI) and 40 patients with Alzheimer's dementia (AD). Our focus was on comparing the performance of PD and aMCI/AD patients in relation to their global cognitive states (operationalized by the Mini Mental Status Examination). We also analyzed qualitative differences in errors of drawing, setting and reading clocks. RESULTS: We found that performance in CDT, but not in the CST or CRT, was impaired earlier in PD than in aMCI/AD. Incorrect placement of the minute hand was the most prominent error in both patient groups. We found no specific influence of visuospatial dysfunction in PD on clock drawing. CONCLUSION: Our findings suggest that executive function related to retrieval of semantic memory about the minute hand is compromised early in PD.

The Mini-Cog versus the Mini-Mental State Examination and the Clock Drawing Test in daily clinical practice: screening value in a German Memory Clinic.

BACKGROUND: The aim of this study was to compare the screening value of the Mini-Cog, Clock Drawing Test (CDT), Mini-Mental State Examination (MMSE) and the algorithm MMSE and/or CDT to separate elderly people with dementia from healthy depending on test time, type and severity of dementia, and demographic variables in a German Memory Clinic. METHODS: Data from a heterogeneous patient sample and healthy participants (n = 502) were retrospectively analyzed. Of the 438 patients with dementia, 49.1% of the dementia diagnoses were Alzheimer's dementia and 50.9% were non-Alzheimer's dementia. Sixty-four participants were classified as cognitively unimpaired. The CDT and an extraction of the 3-item recall of the MMSE were used to constitute the Mini-Cog algorithm. RESULTS: Overall, the Mini-Cog showed significantly higher discriminatory power (86.8%) than the MMSE (72.6% at a cut-off ≤ 24 and 79.2% at ≤ 25, respectively) and CDT (78.1%) (each p < 0.01) and did not perform worse than the algorithm MMSE and/or CDT (each p > 0.05). The specificity of the Mini-Cog (100.0%) was similar to that of the MMSE (100.0% for both cut-offs) and CDT (96.9%) (p = 0.154). For all age and educational groups the Mini-Cog outmatched the CDT and MMSE, and was less affected by education than MMSE and less susceptible for the dementia stage than the CDT. CONCLUSION: The Mini-Cog proved to have superior discriminatory power than either CDT or MMSE and is demonstrated to be a valid "short" screening instrument taking 3 to 4 minutes to administer in the geriatric setting.

Higher BDNF serum levels predict slower cognitive decline in Alzheimer's disease patients.

The neurotrophin brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal survival, synaptic plasticity, and memory. Several recent studies have demonstrated altered BDNF serum levels in Alzheimer's disease (AD) patients. However, the association of BDNF serum levels with the rate of cognitive decline in AD patients is still unclear. We demonstrate that BDNF serum levels are significantly decreased in AD patients with fast cognitive decline [decrease of Mini-Mental State Examination (MMSE) score >4/yr; n=12] compared to AD patients with slow cognitive decline (decrease of MMSE score ≤4/yr, n=28) and show a significant correlation with the rate of cognitive decline during 1 yr follow-up. These results suggest that higher BDNF serum levels are associated with a slower rate of cognitive decline in AD patients. Further longitudinal studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a surrogate marker of disease progression in AD patients.

Identification of a blood-based biomarker panel for classification of Alzheimer's disease.

An ideal diagnostic test for Alzheimer's disease (AD) should be non-invasive and easily applicable. Thus, there is a clear need to search for biomarkers in blood. In the present study, we have used multivariate data analysis [support vector machine (SVM)] to investigate whether a blood-based biomarker panel allows discrimination between AD patients and healthy controls at the individual level. We collected a total of 155 serum samples from individuals with early AD and age-matched healthy controls and measured serum levels of 24 markers involved in several biological pathways by ELISA. The dataset was randomly split into a training set for predictor discovery and classification training and a test set for class prediction of blinded samples (3:1 ratio) to evaluate the chosen predictors and parameters. After selection of a feature group of the three most discriminative parameters (cortisol, von Willebrand factor, oxidized LDL antibodies) in the training set, the application of SVM to the training/independent test dataset resulted in an 81.7%/87.1% correct classification for AD and control subjects. In conclusion, we identified a panel of three blood markers, which allowed SVM-based distinguishing of AD patients from healthy controls on a single-subject classification level with clinically relevant accuracy and validity. Blood-based biomarkers might have utility in AD diagnostics as screening tool before further classification with CSF biomarkers and imaging. Future studies should examine whether blood-based biomarkers may also be useful to differentiate AD patients from other dementias.