Orthostatic hypotension as a risk factor for longitudinal deterioration of cognitive function in the elderly.

BACKGROUND AND PURPOSE: Orthostatic hypotension is frequent with aging with a prevalence of 20%-30% in people aged 65 or older and is considered to increase the risk for coronary events, strokes and dementia. Our objective was to characterize the association of orthostatic hypotension and cognitive function longitudinally over 6 years in a large cohort of the elderly aged over 50 years. METHODS: In all, 495 participants were assessed longitudinally with the Schellong test and comprehensive cognitive testing using the extended CERAD neuropsychological test battery at baseline and after 6 years. In a subgroup of 92 participants, cerebral magnetic resonance imaging was evaluated for white matter changes using a modified version of the Fazekas score. RESULTS: The prevalence of orthostatic hypotension increases with aging reaching up to 30% in participants aged >70 years. Participants with orthostatic hypotension presented with a higher vascular burden index (1.03 vs. 0.69, P ≤ 0.001), tended to have a higher prevalence of cerebral white matter hyperintensities (91.7% vs. 68.8%, P = 0.091) and showed a faster deterioration in executive and memory function (Trail Making Test B 95 vs. 87 s, P ≤ 0.001; word list learning sum -0.53 vs. 0.38, P = 0.002) compared to participants without orthostatic hypotension. CONCLUSION: Orthostatic hypotension seems to be associated with cognitive decline longitudinally.

Effects of home reading training on reading and quality of life in AMD-a randomized and controlled study.

BACKGROUND: Age-related macular degeneration (AMD) causes reading impairment, reduced quality of life (QoL), and secondary depression. We have shown that support with magnifying aids improved reading speed (RS), emotional and cognitive status, and QoL. The present study investigates whether additional reading training (RT) (after adapting to appropriate visual aids) can further improve vision rehabilitation. METHODS: Patients with dry AMD were randomly assigned to 2 groups. The primary RT group (P-RTG, n = 25) trained with sequentially presented text (RSVP), and the control group (CG, n = 12) performed placebo training (crossword puzzles) and later crossed over to RT, so that altogether 37 participants performed reading training. Patients trained at home on a PC for 6 weeks. RS was assessed during reading printed paragraphs of text aloud. Using a scanning laser ophthalmoscope, we examined fixation stability and preferred retinal locus (PRL) for fixating a cross, as well as PRL and eye movements during reading single words. We assessed emotional status by Montgomery-Åsberg Depression Rating Scale (MADRS), cognitive status by dementia detection test ( DemTect ) and QoL by Impact of Vision Impairment (IVI) profile. Visual acuity and magnification requirement were examined by standard procedures. All variables were measured before and after placebo training, before and after RT, and after 6 weeks without training (follow-up). RESULTS: RS improved significantly in the P-RTG during RT, but not in the CG during placebo training. The effect remained stable at follow-up. Fixation performance and eye movement variables did not change. Emotional status (MADRS) improved in P-RTG during RT and showed a significant difference of the change of scores between the 2 groups. Complete IVI scores improved significantly during RT and remained stable. CONCLUSION: The results indicate that patients with AMD, who already use magnifying aids, benefit from additional RT and that it can contribute in preventing depression and improve QoL. TRIAL REGISTRATION: The study was registered at the German Clinical Trials Register (DRKS00015609).

[Recommendations for psychotherapy in psychiatric inpatient treatment : Results of the PAKT Study Part I]. / Psychotherapieempfehlungen in der stationären psychiatrisch-psychotherapeutischen Behandlung : Ergebnisse der PAKT-Studie Teil I.

BACKROUND: In the S3 treatment guidelines psychotherapy is recommended in all psychological disorders. Therefore, outpatient or inpatient psychotherapy should be recommended by therapists in most cases. On the other hand, it is well known that waiting periods for psychotherapeutic treatment are considerable, which raises the question how the recommendation for psychotherapy is presented in psychiatric hospitals in Germany. OBJECTIVES: The article deals with the question of how frequent the recommendation of psychotherapeutic treatment is made after psychiatric inpatient stay or day care, and if there are differences between hospitals and patient groups. METHOD: In four psychiatric hospitals in southern Germany the frequency of recommendation for psychotherapy in psychiatric patients was registered and compared to the number of all patients treated in the equivalent time. For this purpose, we analyzed data of the basic documentation in the four participating hospitals. RESULTS: Overall, 9.6 % of the patients received a recommendation of psychotherapeutic treatment. In the psychiatric university hospital a subsequent psychotherapeutic treatment was recommended somewhat more often. Differences between hospitals were present but marginal. Over all participating hospitals, psychotherapy was recommended markedly less frequently in patients with an F2 diagnosis in comparison with patients with F3 or F4 diagnoses. CONCLUSION: Psychotherapeutic treatment after psychiatric inpatient stay is recommended cautiously. Probably therapists anticipate the fact that the growing demand for psychotherapeutic treatment in general reduces the chances for persons after psychiatric inpatient treatment.

[Implementation of the recommendations for psychotherapy after psychiatric inpatient treatment : Results of the PAKT study Part II]. / Realisierung von Psychotherapieempfehlungen nach psychiatrischem Aufenthalt : Ergebnisse der PAKT-Studie Teil II.

BACKGROUND: Waiting periods for inpatient or outpatient psychotherapeutic treatment are generally considerable. For patients treated in a psychiatric day-clinic or hospital, implementation of a recommended subsequent psychotherapeutic treatment might be difficult. OBJECTIVES: In part II of the psychotherapy after hospital or day clinic (PAKT) study, we examined how the recommendation for psychotherapy can be implemented after psychiatric treatment. MATERIALS AND METHODS: Three months after discharge from one of four psychiatric hospitals in southern Germany, we interviewed 306 patients who received a recommendation for psychotherapeutic treatment after their hospital stays if the recommendation was implemented successfully. RESULTS: Only about 12 % of the patients in the follow-up group were unable to implement the general recommendation for psychotherapy after psychiatric stay despite motivation for psychotherapeutic treatment. In the case of recommendation for outpatient psychotherapy, 20 % were unsuccessful. Predictors for successful implementation were education and employment, whereas variables like age, gender, diagnosis, or severity of disorder did not play a significant role. CONCLUSIONS: The relatively small percentage of unimplemented psychotherapeutic treatment is surprising at a first glance. However, the proportion recommended for psychotherapy after psychiatric stay was less than 10 %, as shown in the first part of the study (see PAKT Study Part I, doi:s00115-016-0107-z).

Substantia nigra hyperechogenicity is related to decline in verbal memory in healthy elderly adults.

BACKGROUND AND PURPOSE: Deficits in cognition have been reported in Parkinson's disease (PD) already in the early and even in the pre-motor stages. Whilst substantia nigra hyperechogenicity measured by transcranial B-mode sonography (TCS) represents a strong PD marker and is associated with an increased risk for PD in still healthy individuals, its association with cognitive performance in prodromal PD stages is not well established. METHODS: Two different cohorts of healthy elderly individuals were assessed by TCS and two different neuropsychological test batteries covering executive functions, verbal memory, language, visuo-constructional function and attention. Cognitive performance was compared between individuals with hyperechogenicity (SN+) and without hyperechogenicity (SN-). RESULTS: In both cohorts, SN+ individuals performed significantly worse than the SN- group in tests assessing verbal memory (word list delayed recall P = 0.05, logical memory II P < 0.017). Significant differences in Mini-Mental State Examination score (cohort 1, P = 0.02) and executive function tests (cohort 2, Stroop Color-Word Reading, P = 0.004) could only be shown in one of the two cohorts. No between-group effects were found in other cognitive tests and domains. CONCLUSIONS: These results indicate that individuals with the PD risk marker SN+ perform worse in verbal memory compared to SN- independent of the assessment battery. Memory performance should be assessed in detail in individuals at risk for PD.

Prodromal features for Parkinson's disease--baseline data from the TREND study.

BACKGROUND AND PURPOSE: A number of non-motor features are known to precede motor manifestations of Parkinson's disease (PD). They are supposed to already represent the prodromal neurodegenerative state in those who later develop PD and are thus called prodromal markers. In this study, three prodromal markers, depression, rapid eye movement behaviour disorder (RBD) and hyposmia, were selected and were related to other prodromal features in elderly individuals without PD. METHODS: From the Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration (TREND) study, 698 healthy individuals aged 50-80 years reporting one or more of the selected prodromal markers (SPMs), but without neurodegenerative disorders, were evaluated and classified according to the status of prodromal markers. Other prodromal PD-related features were assessed with a 23-item questionnaire and compared between participants with and without the three SPMs. RESULTS: Individuals with the SPMs for PD endorsed more of the additional possible prodromal features of PD than those without; of 23 possible prodromal features, the median number identified amongst participants with no SPMs was two, compared with four with one marker, five with two and seven with three (P < 0.001). Regarding individual SPMs, participants with depression and RBD endorsed five of 23 markers, compared with three for those with hyposmia (P = 0.001). There was no significant increase in the number of prodromal features amongst those with two SPMs compared with those with only one marker. CONCLUSIONS: Individuals with the SPMs for PD report a higher prevalence of other prodromal PD symptoms. This may indicate that these markers can identify individuals at risk for PD.

Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment.

OBJECTIVE: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. METHOD: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed-effects regression models for longitudinal data controlling for selection bias by means of propensity scores. RESULTS: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. CONCLUSION: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause.

Psychotropic drug treatment, clinical characteristics and cognitive processing speed in patients with schizophrenia: results from the ELAN study.

INTRODUCTION: Psychotropic drug combinations (PDC) are common in the treatment of patients with schizophrenia but there is little research regarding the effects of PDC on cognition. OBJECTIVE: The aim of this study was to analyse the effects of antipsychotic monotherapy and various types of PDC on cognitive processing speed (CPS). METHODS: ELAN is a 24-month multi-site prospective observational controlled trial following up 374 patients with schizophrenia under routine treatment conditions following discharge from inpatient treatment. The propensity score method, multinomial logistic regression analyses and mixed effects regression models were used. RESULTS: CPS correlated significantly with PANSS and GAF scores and improved over time in the monotherapy group. Negative effects of some PDC (antipsychotics + tranquilizers/antipsychotics+at least 2 other psychopharmacological subclasses, sedative/anticholinergic drugs/high adjusted antipsychotic dose) lost significance after controlling for clinical characteristics. DISCUSSION: Indications for PDC should be examined with care although, in the present study, effects on cognition were small.

BaSAlt - A mixed-methods study protocol on setting-based physical activity promotion and counseling in nursing homes.

INTRODUCTION: Physical activity (PA) is a major contributor to healthy aging. However, physical inactivity is prevalent among the elderly in Germany, particularly in institutionalized settings such as nursing homes. This paper aims to describe the study objectives, design, methods, assessment types, collection schedules and considerations for analyzing the data within the BaSAlt study on facilitators and barriers for PA promotion in nursing homes. METHODS: We designed the BaSAlt study as a participatory intervention study with multiple measurement points in six to eight nursing homes with a total of approx. 200 residents using four main modules: (1) setting-level analysis of physical activity patterns, physical activity-related climate and physical activity-related interaction with 'significant others,' and organizational facilitators and barriers to physical activity, (2) physical-activity related individual-level analysis of objective and self-reported physical activity and sedentary behavior, a geriatric assessment with established procedures, assessment of people's activity and health biographies (biographical mapping) as well as their motivational, subjective well-being and distress status, and (3) a counseling module that integrates counseling at the setting level as well as individual physical activity counseling for residents. In module (4) evaluation, the effects of integrated counseling with regard to the implementation of PA promotion strategies are analyzed. DISCUSSION: This study will extend our knowledge of physical activity promotion in German nursing homes. Its findings will inform governmental authorities, care professionals, and academics on how to reach a particular group, characterized by inactivity, multimorbidity, and a high prevalence of dementia, residing in nursing homes, a setting that will gain further relevance in the future.

[Biological correlates of prefrontal activating and temporoparietal inhibiting treatment with repetitive transcranial magnetic stimulation (rTMS)]. / Biologische Korrelate präfrontal aktivierender und temporoparietal inhibierender Behandlung mit repetitiver transkranieller Magnetstimulation (rTMS).

Repetitive transcranial magnetic stimulation (rTMS) is a tool that enables clinicians and neuroscientists to modulate cortical activity in a non-invasive way. High-frequency rTMS has predominantly an activating effect on the stimulated brain region while low-frequency rTMS has an inhibitory effect. In addition to its usefulness as a research tool and in neurological diagnostics, rTMS may prove useful as a therapeutic option in psychiatry, especially in disorders that are associated with regional changes in cortical activity. For instance, rTMS is under current investigation in the treatment of depression and negative symptoms of schizophrenia. A hypofrontality or a fronto-limbic imbalance associated with both syndromes could be corrected by activating, high frequency rTMS. Conversely, a regional hyperactivity in the temporo-parietal cortex has been described in subjects suffering from auditory hallucinations and tinnitus. Low frequency, inhibitory rTMS is currently evaluated as a therapeutic option in these subjects. In addition to the effects on the directly stimulated brain area, other biological effects of rTMS may exert a beneficial influence on brain function. Amongst these are a modulation of cortico-cortical circuits (e. g. fronto-cingular and fronto-parietotemporal circuits), effects on monoaminergic neuromodulation and neuroendocrine effects. The current knowledge about the therapeutically relevant neurophysiological and neuroendocrine effects of rTMS are reviewed. An improved understanding of the neurophysiological basis of the therapeutic effects of rTMS and of the pathophysiology underlying neuropsychiatric diseases may lead to optimized therapeutic rTMS applications and new clinical indications for rTMS.

[Relapse rate within 6 months after successful ECT: a naturalistic prospective peer- and self-assessment analysis]. / Rückfallraten innerhalb von 6 Monaten nach erfolgreicher EKT--Eine naturalistische prospektive Fremd- und Selbstbeurteilungsanalyse.

BACKGROUND: Up to 100% relapse rate after successful electroconvulsive therapy (ECT) poses a challenge for patients and psychiatrists. The aim of the study was to evaluate the outcome of patients affected by major depression after the successful course of acute ECT. METHODS: 84 patients recruited in a randomized double blind multicenter study designed to investigate the optimal stimulation placement in acute ECT had a follow up under naturalistic conditions between the 5th and 7th month. Outcome, maintenance therapy and patients; attitude were evaluated with semi structured questionnaires by patients and the study raters. RESULTS: 82.14% (68/84) questionnaires of the patients and 83.3% (70/84) of the rater were returned. 98% of the patients had at least one antidepressant; only in 23% (20/68) lithium was prescribed. 35% (7/20) of the patients with lithium and 57% (16/28) without lithium had a relapse within the first 6 months (OR 0.6) in a median of 2.5 months. Only one institution offered maintenance ECT in 8.3% (7/84) patients. For 52.2% of the patients ECT was a helpful treatment an 49.3% would recommend the therapy to their relatives. The vast majority (59.4%) wishes a better information about the ECT and 21.4% feel frightening about the therapy. CONCLUSIONS: The results show a high relapse rate and highlight the meaning of maintenance medication especially for a lithium combination therapy, as stated before. In regard to the subjective sensation the patients claim a better education about the ECT and anyway one of four patients feel frightening about the therapy.

Diverging Awareness of Postoperative Delirium and Cognitive Dysfunction in German Health Care Providers.

PURPOSE: Postoperative cognitive dysfunction (POCD) appears in up to 30% of patients suffering from postoperative delirium (POD). Both are associated with higher mortality and postoperative complications, prolonged hospital stays, and increased costs. Multi-modal models with pre-admission risk reduction counselling, perioperative monitoring, and training of multidisciplinary patient care providers have been shown to decrease the prevalence of both. The aim of our study is to understand how far those measures are known and implemented in routine care and to detect potential gaps in the current practice regarding risk communication and information flow between involved caregivers for patients at risk for POD/POCD. PATIENTS AND METHODS: As part of a multicenter study, seven semi-structured focus group (FG) discussions with nurses and physicians from tertiary care hospitals (surgery, anesthesiology, and orthopedics, n=31) and general practitioners (GPs) in private practice (n=7) were performed. Transcribed discussions were analyzed using qualitative content analysis. RESULTS: POD is present above all in the daily work of nurses, whereas physicians do not perceive it as a relevant problem. Physicians report that no regular risk assessment or risk communication was performed prior to elective surgery. Information about POD often gets lost during hand-offs and is not regularly reported in discharge letters. Thus, persisting cognitive dysfunction is often missed. The importance of standardized documentation and continuous education concerning risks, screening, and treatment was emphasized. The often-suggested pre-OP medication adjustment was seen as less important; in contrast, avoiding withdrawal was regarded as far more important. CONCLUSION: Altogether, it seems that standards and available best practice concepts are rarely implemented. In contrast to physicians, nurses are highly aware of delirium and ask for standardized procedures and more responsibility. Therefore, raising awareness regarding risks, screening tools, and effective preventive measures for POD/POCD seems an urgent goal. Nurses should have a central role in coordination and care of POD to prevent the risk for POCD.

Regenerating adult rat retinal axons reconnect with target neurons in-vitro.

We have established an in-vitro coculture-system of adult rat retina with fetal midbrain explants to examine whether regenerating central nervous system axons are still able to recognize appropriate target neurons. Our results show that the retinal ganglion cell axons regenerate their axons and reinnervate the retino-recipient areas of cocultured fetal midbrain slices after one to seven weeks in-vitro. Functional connections as defined by electrophysiological criteria are detected only within these areas.

Flunarizine enhances rat retinal ganglion cell survival after axotomy.

After axotomy most central nervous neurons including retinal ganglion cells (RGCs) die in a few weeks, although their somata are not injured. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors or due to a calcium overload after excessive release of excitatory amino acids from dying cells. Flunarizine, as a potent blocker of voltage dependent Ca2+ channels and in higher concentration being an inhibitor of the Ca2+/calmodulin-dependent protein kinase II, is able to mimic the neurotrophic effect of NGF on dorsal root ganglion (DRG) neurons. To examine its neuroprotective value in the central nervous system (CNS), flunarizine (5 mg/kg body weight) was given daily to rats after unilateral axotomy of the optic nerve. The density of retrogradely labelled retinal ganglion cells (RGCs) was determined 14 days after axotomy. It could be demonstrated that flunarizine significantly enhanced RGC survival after axotomy in adult rats (P < 0.001; 1065 +/- 142 vs. 922 +/- 237 RGCs/mm2).

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression.

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.

Postoperative psychosis in homocystinuria.

Young homocystinuria patients suffering from lens dislocation frequently have to undergo eye surgery. We describe a 16-year-old girl with mild mental retardation who became psychotic-delirant immediately after the last of three lentectomia operations performed under general thiopental anaesthesia. Because methionine, homocysteine, its oxidation product homocysteate and cysteine are potent glutamate agonists, the disturbance of the sulphur containing amino acid (SCAA) metabolism in homocystinuria patients may alter the function of cerebral glutamatergic transmission. The chronic and acute neurological and psychiatric symptoms of homocystinuria patients offer a clue to studies of the neurotoxic but also antipsychotic potency of glutamate agonists like the SCAAs in humans.

Psychiatric commitment: patients' perspectives.

OBJECTIVE: The literature pertaining to patients' perceptions of commitment and its consequences is limited. The object of this study was to learn more about these experiences from the patient's perspective. MATERIAL AND METHODS: 108 court-committed patients (78% of whom were schizophrenic) were identified for inclusion in a retrospective follow-up study. After an interval varying from one to 4.5 years from time of commitment to follow-up, 76 patients could be contacted, of whom 47 were included in the follow-up. RESULTS: The majority of patients felt that their court commitment had not been justified and could have been avoided. Events and circumstances identified as particularly stressful about commitment were confinement in a locked ward, side effects of medication, feelings of helplessness, and certain staffbehaviors. Adverse psychological, somatic, and social consequences were common. Coercive measures during hospitalization were strongly associated with negative feelings about the effect of commitment on mental health and about subsequent treatment. The majority, however, also remained in treatment after commitment was terminated, said they would return to hospital in event of future crisis, and had pertinent comments about how commitment could have been avoided. CONCLUSIONS: Many patients who had been court-committed reported negative feelings about their experiences, but the great majority had continued in treatment, both at the termination of commitment and later. They also had ideas about how to reduce the negative impact of commitment that are worth including in future contingency plans.

[The influence of visual rehabilitation on secondary depressive disorders due to age-related macular degeneration. A randomized controlled pilot study]. / Einfluss visueller Rehabilitation auf sekundäre depressive Störungen bei altersabhängiger Makuladegeneration. Eine randomisierte kontrollierte Pilotstudie.

BACKGROUND: Age-related macular degeneration (AMD) often leads to visual impairment, loss of reading ability, reduced quality of life and secondary depression. The present study examined if visual rehabilitation has a preventive effect on secondary depression in these patients. MATERIAL AND METHODS: In a controlled pilot study 20 patients were randomized into 2 groups whereby 9 underwent visual rehabilitation at first examination and 11 received magnifying visual aids only after 3 months. Psychosocial status was assessed by the geriatric depression scale (GDS) and the German version of the Centre for Epidemiologic Studies depression (CES-D) scale (main outcome parameter), cognitive status by the dementia detection test (DemTecT), minimental status (MMS) and quality of life by the National Eye Institute visual function questionnaire (NEI-VFQ 25). Ophthalmological examination included reading speed measurement by standardized texts (International Reading Speed Texts; IReST). RESULTS: Parameters of the CES-D scale, DemTect and the subitem exercise of social roles of the NEI-VFQ 25 emerged in a divergent manner. Patients of the rehabilitation group became less depressive and improved in cognitive and social abilities and in the control group vice versa. The interactive effect of group and time was statistically significant for all three tests. CONCLUSIONS: Visual rehabilitation has a positive impact on depression as well as cognitive status and quality of life in patients with AMD. The effects have to be confirmed in future studies with more patients and a longer observation period.

Macrophage colony-stimulating factor (M-CSF) in plasma and CSF of patients with mild cognitive impairment and Alzheimer's disease.

Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that activates microglial cells, involved in phagocytosis of amyloid-beta (Abeta) in the brain. In the present study, we found in 50 patients with Alzheimer's disease (AD) significantly increased M-CSF plasma levels compared to 22 patients with mild cognitive impairment (MCI) and 35 age-matched healthy controls. In contrast, MCI patients showed significantly decreased M-CSF levels in cerebrospinal fluid (CSF) compared to AD patients and 20 patients with other non-inflammatory neurological disease (NIND). Analyzing the impact of Beta-amyloid 1-42 (Abeta 1-42), tau protein and M-CSF for differentiation between the groups we found that M-CSF, but not Abeta 1-42 and tau-protein is a significant parameter for distinction between MCI and NIND patients with 68.8% sensitivity and 75.0% specificity. M-CSF CSF levels < or = 357.8 pg/ml yielded 73.7% sensitivity and 75.0% specificity for diagnosing MCI patients in comparison with control subjects. In conclusion, our data indicate that M-CSF in CSF could be a putative biomarker for MCI.

Increase of BDNF serum concentration during donepezil treatment of patients with early Alzheimer's disease.

Alzheimer's disease (AD) can be treated with inhibitors of the enzyme acetylcholinesterase (AChE). Recent pre-clinical and clinical studies gave evidence that AChE-inhibitors have neuroprotective effects and thereby a disease-modifying potential. The mechanism of this action is still discussed. In an animal model oral administration of an AChE-inhibitor lead to an increase of brain derived neurotrophic factor (BDNF) in hippocampus and cortex. Recent studies have found a decrease of BDNF in the serum and brain of AD patients with potentially consecutive lack of neurotrophic support and contribution to progressive neurodegeneration. BDNF serum concentrations were assessed by ELISA in 19 AD patients and 20 age-matched healthy controls at baseline and in the AD patients after 15 months of treatment with donepezil 10 mg per day (one patient received just 5 mg). Before treatment with donepezil we found in AD significantly decreased BDNF serum concentrations (19.2 +/- 3.7 ng/ml) as compared to healthy controls (23.2 +/- 6.0 ng/ml, P = 0.015). After 15 months of treatment the BDNF serum concentration increased significantly in the AD patients (23.6 +/- 7.0 ng/ml, P = 0.001) showing no more difference to the healthy controls (P = 0.882). The results of the present study confirm data of prior investigations that a down-regulation of BDNF in serum and brain of AD patients seems to begin with the first clinical symptoms and to be persistent. A treatment with the AChE-inhibitor donepezil is accompanied with an increase of BDNF serum concentration in AD patients reaching the level of healthy controls. Thus, up-regulation of BDNF might be part of a neuroprotective effect of AChE-inhibitors. The molecular mechanism of this potentially disease-modifying mechanism of action of donepezil should be clarified.