[Brain health services: individual dementia risk profiling at the Cologne Alzheimer Prevention Center]. / Brain Health Services: Erfassung des individuellen Demenzrisikos am Kölner Alzheimer Präventionszentrum.

BACKGROUND: According to current knowledge approximately 30-40% of all cases of dementia can be attributed to modifiable risk factors. As a result, dementia prevention and the concept of brain health are becoming increasingly relevant. RESEARCH QUESTION: The requirements for brain health services and their implementation are discussed and the Cologne Alzheimer Prevention Center (KAP) of the University Hospital Cologne is described as an example. MATERIAL AND METHODS: In addition to a report on international brain health initiatives, the main activities of the KAP are presented. A program for individual risk profiling and risk communication is provided, which was piloted in the KAP in the context of the "Individual risk profiling for Alzheimer's disease and dementia prevention (INSPIRATION)" study. The prevalence of risk factors in a cognitively healthy sample aged 50-86 years (n = 162) with interest in dementia prevention is presented. RESULTS: The most common risk factors were non-Mediterranean diet, obesity, subjective poor sleep quality and increased stress. Based on these results, preventive interventions can be developed that are adapted to the individual risk profile as a personalized medicine approach. DISCUSSION: Structures such as the KAP can provide individual risk factor assessment and personalized dementia prevention. The efficacy of this approach on dementia risk reduction needs to be evaluated.

Description of a European memory clinic cohort undergoing amyloid-PET: The AMYPAD Diagnostic and Patient Management Study.

INTRODUCTION: AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost-effectiveness of amyloid-PET in Europe. Here we present participants' baseline features and discuss the representativeness of the cohort. METHODS: Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia were recruited in eight European memory clinics from April 16, 2018, to October 30, 2020, and randomized into three arms: ARM1, early amyloid-PET; ARM2, late amyloid-PET; and ARM3, free-choice. RESULTS: A total of 840 participants (244 SCD+, 341 MCI, and 255 dementia) were enrolled. Sociodemographic/clinical features did not differ significantly among recruiting memory clinics or with previously reported cohorts. The randomization assigned 35% of participants to ARM1, 32% to ARM2, and 33% to ARM3; cognitive stages were distributed equally across the arms. DISCUSSION: The features of AMYPAD-DPMS participants are as expected for a memory clinic population. This ensures the generalizability of future study results.

Stress and Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Due to demographic change in higher income countries and rising life expectancy in middle- and low-income countries, the prevalence of AD will increase significantly in the coming years. In the search for effective AD prevention, the role of stress in the development of AD has come into focus. There is increasing evidence that chronic exposure to stress is a risk factor for AD and may also adversely affect the course of the disease. In our review, we present the current literature on the association of specific personality traits and the risk of developing AD. We also report on findings on dementia risk in patients with posttraumatic stress disorder. Furthermore, we describe the role of anxiety symptoms in AD and give a brief overview over the biological mechanisms behind the association of stress and AD.

[Prevention of cognitive decline and dementia by treatment of risk factors]. / Prävention von kognitivem Abbau und Demenz durch Behandlung von Risikofaktoren.

BACKGROUND: In Germany, approximately 1.6 million people are currently suffering from dementia. The prevalence of the disease is expected to double by 2060. To date there is no treatment that can prevent the onset of dementia. For this reason, the development of prevention strategies for cognitive decline and dementia is crucial. OBJECTIVE: Presentation of studies on dementia prevention by treatment of arterial hypertension. Overview of current multidomain interventional studies on dementia prevention. MATERIAL AND METHODS: Narrative review. RESULTS: Whereas in three previous randomized controlled trials on antihypertensive treatment a reduction of dementia risk could not be found, the recent SPRINT-MIND study demonstrated a reduced risk of mild cognitive impairment (MCI) and in the trend for dementia by intensified hypotensive treatment. Multidomain interventional studies suggest preventive effects, particularly in specific risk groups and also highlight the challenge of adherence to lifestyle modifications. CONCLUSION: The treatment of modifiable risk factors can have a preventive effects on cognitive decline and dementia. More research is needed to identify subgroups with the greatest likelihood of benefits.

Long-term treatment of chronic migraine with OnabotulinumtoxinA: efficacy, quality of life and tolerability in a real-life setting.

Botulinum toxin was shown to be effective in treatment of chronic migraine. We wanted to explore its efficacy and tolerability in chronic application under real-life conditions. For this, 27 consecutive patients (age 45.6 ± 10.8 years, 25 females, 2 males) received altogether 176 injection series (IS) with 189.7 ± 45.8MU onabotulinumtoxinA (Botox(®)) according to the PREEMPT scheme. During the study period altogether 6.5 ± 2.9 (min 4, max 13) IS were applied per patient (total treatment time of 73.1 ± 36.9 weeks). 96 % of the patients reported benefit. Monthly headache days were reduced from 18.9 ± 3.9 to 8.7 ± 4.5 (p < 0.001, -53.7 %), migraine days from 16.8 ± 4.9 to 7.4 ± 4.6 (p < 0.001, -55.1 %), autonomic days from 8.6 ± 7.5 to 2.7 ± 4.2 (p < 0.001, -71.9 %) and medication days from 14.2 ± 4.6 to 8.3 ± 4.2 (p < 0.001, -71.1 %). Health-related quality of life improved by 0.6-1.5 standard deviations (SD) (Short Form Health Survey), migraine-related quality of life by 1.4-2.0 SD (Migraine-Specific Quality of Life Questionnaire) and by 1.9 SD (Headache Impact Test), depression by 1.1 SD (Beck Depression Inventory). Subjective global clinical improvement was 2.6 ± 0.6 (Global Clinical Improvement Scale). All improvements were stable throughout the entire study period. Adverse effects were infrequent, mild and transient. Botulinum toxin provides highly effective and safe long-term treatment of chronic migraine.

Body Concept and Quality of Life in Patients with Idiopathic Dystonia.

Patients with dystonia experience unusual postures and disfigurement. The aim of the study was to examine changes in the body concept in relation to quality of life and severity of dystonia. Our cohort consisted of 20 patients with idiopathic dystonia resistant to medical therapy who were planned for pallidal deep brain stimulation. The results were compared to 25 healthy controls. The patients were assessed with Frankfurt Body Concept Scale, Short Form 36 (SF-36) Health Survey, Hamilton Depression Scale, Beck Depression Inventory, Social Phobia Inventory and Social Interaction Anxiety Scale. The disease severity was evaluated with Burke-Fahn-Marsden Dystonia Rating Scale and Toronto Western Spasmodic Torticollis Rating Scale. Patients with dystonia had a significantly impaired body concept in eight out of nine subscales in comparison to healthy controls. The differences were most pronounced for the subscales general health, body care, physical efficacy, sexuality and physical appearance (p < 0.001). Furthermore, all eight subscales of SF-36 exhibited significantly lower values in patients with dystonia compared to controls. We also found significant positive correlations between SF-36 and body concept subscales. Impairment of body concept was not associated with disease severity or levels of social anxiety symptoms. However, there was a significant association between self-rated depression and disease severity. Our patients suffered from increased depression and social anxiety symptoms except social interaction anxiety. We conclude that patients with dystonia have significant body concept impairment that interferes with quality of life in both physical and emotional domains. Future studies should focus on assessing these symptoms after adequate therapeutic management of motor symptoms.

Botulinum neurotoxin serotype D - A potential treatment alternative for BoNT/A and B non-responding patients.

OBJECTIVES: Botulinum neurotoxin serotypes A and B (BoNT/A & B) are highly effective medicines to treat hyperactive cholinergic neurons. Due to neutralizing antibody formation, some patients may become non-responders. In these cases, the serotypes BoNT/C-G might become treatment alternatives. BoNT/D is genetically least related to BoNT/A & B and thereby circumventing neutralisation in A/B non-responders. We produced BoNT/D and compared its pharmacology with BoNT/A ex vivo in mice tissue and in vivo in human volunteers. METHODS: BoNT/D was expressed recombinantly in E. coli, isolated by chromatography and its ex vivo potency was determined at mouse phrenic nerve hemidiaphragm preparations. Different doses of BoNT/D or incobotulinumtoxinA were injected into the extensor digitorum brevis (EDB) muscles (n = 30) of human volunteers. Their compound muscle action potentials were measured 11 times by electroneurography within 220 days. RESULTS: Despite a 3.7-fold lower ex vivo potency in mice, a 110-fold higher dosage of BoNT/D achieved the same clinical effect as incobotulinumtoxinA while showing a 50% shortened duration of action. CONCLUSIONS: BoNT/D blocks dose-dependently acetylcholine release in human motoneurons upon intramuscular administration, but its potency and duration of action is inferior to approved BoNT/A based drugs. SIGNIFICANCE: BoNT/D constitutes a potential treatment alternative for BoNT/A & B non-responders.

Botulinum toxin in the management of chronic migraine: clinical evidence and experience.

Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox®) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM.