Cochlear implant therapy improves the quality of life and social participation in the elderly: a prospective long-term evaluation.

PURPOSE: In recent years, the number of elderly cochlear implant (CI) candidates is continuously rising. In addition to the audiological improvement, other positive effects of CI treatment can also be observed in clinical routine. The "quality of life" as a parameter of success directly experienced by the patient is increasingly becoming the focus of clinical research. Although there are already clear indications of a rapid and significant improvement in quality of life, there is still a lack of systematic, prospectively collected longitudinal long-term data in patients over the age of 65. METHODS: This prospective longitudinal observational study included 31 patients between the age of 71 and 92 years who had first been treated unilaterally with a CI 6 years ago. In addition to free-field monosyllable recognition, quality of life was assessed using the World Health Organization Quality-of-Life Scale-old (WHOQL-OLD). The results were compared with the data from our previous study, in which we focused on the short- and medium-term effects on quality of life. In both studies, the same patient population was examined. In addition, these study data were compared with an age-matched average population. RESULTS: In speech recognition, there was no significant change from the control 6 months postoperatively compared with the results 6 years postoperatively. No significant changes occurred in the total quality of life score or any of the other six facets of quality of life when comparing the results 6 months postoperatively with the results 6 years postoperatively. In "Social participation", the CI patients even exceed the values of the age-matched average population 6 years after treatment. CONCLUSION: Improvement in the quality of life and especially in social participation appears stable over many years in elderly patients after hearing rehabilitation with a CI.

[Cochlear implants reduce tinnitus in older patients in the long term]. / Eine Cochlea-Implantat-Versorgung reduziert langfristig die Tinnitusbelastung bei älteren Patienten.

BACKGROUND: Tinnitus is one of the most common otologic comorbidities, particularly in older patients with severe hearing loss or deafness. Cochlear implants (CI) have been used for hearing rehabilitation more and more successfully in elderly patients and CI treatment is performed in Germany without an age limit. The aim of this follow-up study was to assess the tinnitus burden in the long-term follow-up of elderly patients with hearing rehabilitation using CI. MATERIAL AND METHODS: This prospective longitudinal study included 15 patients between 72 and 92 years of age with preoperative tinnitus who had been treated unilaterally with a CI for the first time about six years ago. Monosyllabic speech understanding and tinnitus burden were assessed using the Mini-Tinnitus Questionnaire. The results were compared with our previous study 24, focusing on the first six months. RESULTS: Six years postoperatively, there was a nonsignificant increase in monosyllabic understanding to 61.7 ± 26.3%, compared with the results six months postoperatively (p = 0.069). The burden of tinnitus showed a stable low mean of 3.9 ± 3.6 points six years postoperatively, compared with the six-month control (p = 0.689) and significantly reduced compared to the preoperative status with 6.9 ± 6.5 points (p = 0.016). CONCLUSION: Hearing rehabilitation by using CI leads to a stable improvement of monosyllabic discrimination in elderly people as well as to a stable reduction of tinnitus burden over years.

Empowering patients with dementia to make legally effective decisions: a randomized controlled trial on enhancing capacity to consent to treatment.

Objectives: As our society ages, the incidence of age-related diseases increases and with it the number of medical treatments that require informed consent. Capacity to consent is often categorically questioned in persons with dementia (PwD) without appropriate assessment, depriving them of their right to autonomous decision-making. Supportive structures for PwD that comply with legal requirements are lacking. The EmMa project tried to overcome this shortcoming by developing and testing possible supportive measures to enhance the informed consent process for PwD.Method: These enhanced consent procedures (ECPs) were tested in a randomized controlled trial with 40 PwD. It was hypothesized that strengths-based ECPs could improve capacity to consent to a drug treatment in PwD as measured with a semi-structured interview.Results: Against the expectations, no effect of the ECPs on capacity to consent could be found, but the ECPs improved understanding of information in PwD.Conclusion: To empower PwD in clinical settings, however, all aspects of capacity to consent should be targeted with specific aids that are implemented carefully and selectively. More research on possible aids for ECPs is urgently needed in order to enable ethically and legally robust informed consent. In particular, effective ways to improve both reasoning and appreciation are yet to be found.

[Mild cognitive impairment in geriatric practice: patient orientation, diagnostics, treatment and ethics]. / Leichte kognitive Beeinträchtigung (MCI) in der altersmedizinischen Praxis: Patientenorientierung, Diagnostik, Behandlung und Ethik.

Mild cognitive impairment (MCI) is a common problem in old people, which can be distressing for patients and their families. The main feature of MCI is a decrease in cognitive performance with activities of daily living still unimpaired. The identification of treatable risk factors, recognition of early cognitive changes and a timely differential diagnosis, comprehensive information and counselling are important tasks in geriatric medicine. The aim of this article is to present practical recommendations to support physicians working with geriatric patients in recognizing cognitive deficits at an early stage, provide high-quality care focusing on counselling, treatment, and comorbidity management and to maximize the potential of the available treatment options.

[Strengthening prevention and health promotion in and for old age]. / Prävention und Gesundheitsförderung im und für das Alter stärken.

BACKGROUND: Disease prevention and health promotion in and for old age have become increasingly more important. Nevertheless, more (national) research and implementation in practice is needed, as the international comparison shows. OBJECTIVE: To develop guiding principles for research and practice on prevention and health promotion in and for old age. MATERIAL AND METHODS: As part of an iterative process, members of the German Society of Gerontology and Geriatrics came together in workshops and symposia to formulate key guiding principles and fields of action for prevention and health promotion. RESULTS: The following were worked out: 1) prevention and health promotion are useful and possible up to oldest age, 2) prevention and health promotion for advanced age should start early, 3) prevention and health promotion must take into account the diversity and heterogeneity of the life situations of old people, 4) prevention and health promotion promote and demand self-determination and participation, 5) prevention of multiple illnesses must be given greater attention, 6) prevention of the need for long-term care and prevention in long-term care must be treated equally, 7) prevention and health promotion must be thought of in terms of life worlds and across sectors, paying particular attention to aspects of social inequality and a focus on resources, 8) prevention and health promotion and the related research must be interdisciplinary and transdisciplinary and be applied at different levels, from molecular to societal. DISCUSSION: The guiding principles outline the focal points of future-oriented ageing, health and healthcare research and open up fields of action but also show the limits of this approach for political decision-makers, researchers and practitioners.

[Non-pharmacological Therapies of Dementia - an Update]. / Nicht pharmakologische Therapien bei Demenz.

Non-pharmacological Therapies of Dementia - an Update Abstract: Non-pharmacological interventions for people with dementia are intended to improve quality of life and well-being, alleviate psychopathological and behavioral symptoms, and also offer caregivers support and opportunities to promote resilience. Against the background of the multiple failures in the field of pharmacological-therapeutic research, these approaches have become increasingly important. This is an up-to-date overview of the most important non-drug interventions for people with dementia and related recommendations for therapeutic use according to the current state of research and the recommendations of AWMF S3 guideline "dementia". The most important interventions from this therapeutic spectrum are cognitive stimulation to maintain cognitive functioning, physical activation, and creative therapeutic offers to promote communication skills and social participation. In the meantime, access to these diverse psychosocial interventions has also been supplemented by digital technology. What these interventions have in common is that they are based on the individual cognitive and physical resources of those affected, improve quality of life and mood, and promote participation and self-efficacy. In addition to psychosocial interventions, nutrition-related approaches ("medical food") and non-invasive neurostimulation have recently also shown potential in the context of non-drug therapy for people with dementia.

Don't forget about tau: the effects of ApoE4 genotype on Alzheimer's disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment-data from the Dementia Competence Network.

ApoE4, the strongest genetic risk factor for Alzheimer's disease (AD), has been shown to be associated with both beta-amyloid (Aß) and tau pathology, with the strongest evidence for effects on Aß, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF Aß42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF Aß42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF Aß42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4 + carriers having decreased CSF Aß 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and Aß42 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-ß burden and tau aggregation at specific time points in AD pathogenesis.

Long-term effects on the quality of life following cochlear implant treatment in older patients.

PURPOSE: Even in older patients, hearing rehabilitation with a cochlear implant has become an established method for deafened or severely hearing-impaired patients. In addition to the hearing improvement, numerous other effects of CI treatment can be observed in clinical routine. In the literature, there is multiple evidence for a rapid and significant improvement in quality of life with CI treatment. The aim of this study was to evaluate the long-term effects of hearing rehabilitation using CI on the quality of life in older patients (≥ 65 years). METHODS: This prospective cross-sectional study examined 84 patients between the age of 65 and 101 years who received unilateral CI treatment for the first time between one and 10 years ago. The World Health Organization Quality-of-Life Scale-Old (WHOQL-OLD) was used to determine the quality of life. The study cohort was divided into three groups to compare the quality of life over time: group I (1-3 years after CI treatment), group II (4-6 years after CI treatment), and group III (7-10 years after CI treatment). In addition, the data from this study were compared with the results of our previous study (Issing et al. 2020) in which we focused on the first 6 months after CI treatment. RESULTS: In all three groups, there was a significant improvement in monosyllabic discrimination within 1 year after CI fitting (p > 0.001). No significant differences were found between the three groups. There were no significant differences between the three groups in the WHOQOL-OLD total score (p = 0.487) or any of the other six facets. Moreover, no significant differences were found compared to the study group of our previous study 6 months after CI treatment. CONCLUSION: This study demonstrates the long-term stability of the improved quality of life following unilateral CI treatment in patients aged 65 years or older.

Person-environment fit of environmental support provided during medical consultations with older patients.

As some cognitive functions decline in old age, the ability to decide about important life events such as medical treatment is endangered. Environmental support to improve the comprehension of health-related information is therefore necessary. With a small-scale explorative approach, the present survey study aimed at investigating person-environment fit (PE-fit) of support provided during medical consultations. This fit was calculated by assessing the match between aids provided by five medical practitioners during medical consultations and aids most appreciated by the geriatric patients (N = 88). The results showed that the largest discrepancies of used and appreciated aids could be found concerning the opportunity to discuss decisions with relatives, the possibility to take notes, the use of objects, pictures and a keyword list. Female patients indicated a lower PE-fit. These findings highlight discrepancies between the use of specific aids and the wishes of patients and call for thoughtful use of aids during consultations with geriatric patients.

Association of dietary fat composition with cognitive performance and brain morphology in cognitively healthy individuals.

BACKGROUND: Dietary lipids (omega-3 polyunsaturated fatty acids (n-3) PUFAs) and saturated fatty acids (SFA) seem to play an important role in brain health. (n-3) PUFAs have been shown to improve cerebral perfusion and to promote synaptogenesis. In this study, we investigated the relationship between dietary fat composition, cognitive performance and brain morphology in cognitively healthy individuals. METHODS: A total of 101 cognitively healthy participants (age: 42.3 ± 21.3 years, 62 females) were included in this study. Verbal memory was assessed using the California Verbal Learning Test (CVLT). Intake of (n-3) PUFA and SFA was calculated from food-frequency questionnaire-derived data (EPIC-FFQ). Magnetic resonance imaging (MRI) data were obtained (Siemens Trio 3T scanner) and grey matter volumes (GMV) were assessed by voxel-based morphometry (VBM/SPM8). We examined the association of SFA/(n-3) PUFA ratio and memory performance as well as GMV using regression models adjusted for age, sex, education, body mass index, apolipoprotein E (APOE) status and alcohol consumption. For VBM data, a multiple regression analysis was performed using the same covariates as mentioned before with intracranial volume as an additional covariate. RESULTS: A high SFA/(n-3) PUFA ratio was significantly (p < 0.05) correlated with poorer verbal memory performance and with lower GMV in areas of the left prefrontal cortex that support memory processes. CONCLUSIONS: These findings suggest that a diet rich in PUFAs is likely to exert favourable effects on brain morphology in brain areas important for memory and executive functions. This could constitute a possible mechanism for maintaining cognitive health in older age.

[Capacity to consent of people with dementia : Insights into the S2k AWMF guidelines 108-001]. / Einwilligungsfähigkeit von Menschen mit Demenz : Einblicke in die S2k-AWMF-Leitlinie 108 ­ 001.

People with dementia often require medical and nursing care and are regularly confronted with the need to make decisions in this respect; however, in practice uncertainty often exists as to whether a person with dementia is capable of providing consent, what procedures should be used to obtain informed consent, how to provide the necessary information and how capacity to consent can be assured. By providing structured practical recommendations, the S2k guidelines "Consent of persons with dementia to medical treatment" (coordinated by the Association of the Scientific Medical Societies of Germany, AWMF, registration number 108-001) provide a first attempt to summarize and update the relevant medical, legal, ethical and psychological requirements that should be satisfied in this respect. This article enables insights into the guidelines and an overview of the most important recommendations.

[Hearing rehabilitation using a cochlear implant - a way of reducing tinnitus in the elderly]. / Die Hörrehabilitation mittels Cochlea-Implantat ­ Eine Möglichkeit der Tinnitus-Reduktion im Alter.

BACKGROUND: Tinnitus is a common symptom of severe hearing loss or deafness especially in older people. Hearing rehabilitation for these patients is usually only possible with a cochlear implant (CI). In recent years, an increasing number of old and very old patients have been treated with a CI. The aim of this study was to examine the influence of hearing rehabilitation with a CI on the tinnitus of older people. MATERIALS AND METHODS: In this prospective study 34 patients between the age of 65 and 86 were included, who were unilaterally treated with a CI for the first time. 16 patients (47.1 %) had tinnitus preoperatively. At three time points (preoperative, on initial fitting and six months postoperatively), tinnitus severity was assessed in addition to speech discrimination in patients with tinnitus using the mini-tinnitus questionnaire (Mini-TF12). RESULTS: Six month postoperatively we found a highly significant improvement of speech discrimination (preoperatively 11.5 ±â€Š17.4, six-month visit 54.4 ±â€Š28.1 %, p = 0.001) that was accompanied by a highly significant reduction in tinnitus severity according to Mini-TF12 scores (preoperatively 6.9 ±â€Š6.5, six-month visit 4.3 ±â€Š3.3, p = 0.001). CONCLUSIONS: Hearing rehabilitation by means of CI leads to a highly significant reduction of tinnitus severity of pre-operatively existing tinnitus in the elderly.

[Capacity to consent of people with dementia : Insights into the S2k AWMF guidelines 108-001]. / Einwilligungsfähigkeit von Menschen mit Demenz : Einblicke in die S2k-AWMF-Leitlinie 108 ­ 001.

People with dementia often require medical and nursing care and are regularly confronted with the need to make decisions in this respect; however, in practice uncertainty often exists as to whether a person with dementia is capable of providing consent, what procedures should be used to obtain informed consent, how to provide the necessary information and how capacity to consent can be assured. By providing structured practical recommendations, the S2k guidelines "Consent of persons with dementia to medical treatment" (coordinated by the Association of the Scientific Medical Societies of Germany, AWMF, registration number 108-001) provide a first attempt to summarize and update the relevant medical, legal, ethical and psychological requirements that should be satisfied in this respect. This article enables insights into the guidelines and an overview of the most important recommendations.

How do dementia researchers view support tools for informed consent procedures of persons with dementia?

The study aimed to assess how dementia researchers view eight support tools that have been defined to enhance informed consent (IC) procedures for people with dementia (PwD). In an online survey, 19 dementia researchers from Germany and Portugal evaluated the tools in terms of 4 implementation criteria. Overall, they all had a very positive attitude towards the support tools, whereby the tools person-centered attitude of the researcher and elaborated plain language were the most highly rated of the eight tools. Our findings also indicated that familiar support tools were assessed more favorably than those that were previously unknown. Overall, the results of this study showed that the participating dementia researchers were open to the use of decision support measures in PwD and were willing to apply the support tools in practice.

Exercise and microstructural changes in the motor cortex of older adults.

Exercise has been shown to counteract age-related volume decreases in the human brain, and in this imaging study, we ask whether the same holds true for the microstructure of the cortex. Healthy older adults (n = 47, 65-90 years old) either exercised three times a week on a stationary bike or maintained their usual physical routine over a 12-week period. Quantitative longitudinal relaxation rate (R1 ) magnetic resonance imaging (MRI) maps were made at baseline and after the 12-week intervention. R1 is commonly taken to reflect cortical myelin density. The change in R1 (ΔR1 ) was significantly increased in a region of interest (ROI) in the primary motor cortex containing motor outputs to the leg musculature in the exercise group relative to the control group (p = .04). The change in R1 in this ROI correlated with an increase in oxygen consumption at the first ventilatory threshold (VT1) (p = .04), a marker of improvement in submaximal aerobic performance. An exploratory analysis across the cortex suggested that the correlation was predominately confined to the leg representation in the motor cortex. This study suggests that microstructural declines in the cortex of older adults may be staved off by exercise.

Intrinsic functional connectivity, CSF biomarker profiles and their relation to cognitive function in mild cognitive impairment.

Mild cognitive impairment (MCI) often precedes Alzheimer's Dementia (AD), and in a high proportion of individuals affected by MCI, there are already neuropathological processes ongoing that become more evident when patients progress to AD. Accordingly, there is a need for reliable biomarkers to distinguish between normal aging and incipient AD. Recent research suggests that, in addition to established biomarkers such as CSF Aß42, total tau and hyperphosphorylated tau, resting state connectivity established by functional magnetic resonance imaging might also be a feasible biomarker for prodromal stages of AD. In order to explore this possibility, we investigated resting state functional connectivity as well as cerebrospinal fluid (CSF) biomarker profiles in patients with MCI (n = 30; age 66.43 ± 7.06 years) and cognitively healthy controls (n = 38; age 66.89 ± 7.12 years). CSF Aß42, total tau and hyperphosphorylated tau concentrations were correlated with measures of cognitive performance (immediate and delayed recall, global cognition, processing speed). Moreover, MCI-related alterations in intrinsic functional connectivity within the default mode network were investigated using functional resting state MRI. As expected, MCI patients showed decreased CSF Aß42 and increased total tau concentrations. These alterations were associated with cognitive performance. However, there were no differences between MCI patients and cognitively healthy controls regarding intrinsic functional connectivity. In conclusion, our results indicate that CSF protein profiles seem to be more closely related to cognitive decline than alterations in resting state activity. Thus, resting state connectivity might not be a reliable biomarker for early stages of AD.

Lifespan leisure physical activity profile, brain plasticity and cognitive function in old age.

OBJECTIVES: Despite the evidence suggesting physical activity (PA) as a major factor for the prevention of age-related cognitive decline, only a few studies have systematically investigated the impact of leisure PA during the lifespan (LLPA). This study investigates the effects of LLPA on cognitive function (CF) and brain plasticity (BP) in old age. METHOD: Participants' (n = 50, 72 ± 5 yrs, 27 females) LLPA energy expenditure and volume was assessed via a validated questionnaire investigating five epochs (14-80 yrs). Using current WHO PA recommendations as reference, participants were stratified into energy expenditure and volume groups. CF outcomes were attention, executive functions, working memory and memory. BP was assessed using magnetic resonance spectroscopy (MRSI) and brain derived neurotropic factor (BDNF). RESULTS: Correlation analysis revealed associations of mean LLPA energy expenditure with attention (CF) and N-acetylaspartate to choline ratios (NAA/Cho) (MRSI). ANOVA revealed higher interference control performance (CF) and NAA/Cho in participants complying with current PA recommendations (2-3 h per week) compared to non-compliers. Further CF and BP outcomes including BDNF were not associated with LLPA. CONCLUSION: Lifelong adherence to minimum recommended PA seems to be associated with markers of cognitive function and neuronal integrity in old age.

[Emotional robots in a nursing context : Empirical analysis of the present use and the effects of Paro and Pleo]. / Emotionale Roboter im Pflegekontext : Empirische Analyse des bisherigen Einsatzes und der Wirkungen von Paro und Pleo.

BACKGROUND: It has been questioned by researchers in robotics as well in the general public to what extent companion-type robots can support the elderly with the fulfillment of their psychological and social needs. Although these robots have already been used in care settings in Germany, research has referred little to this practical experience in order to analyze their impact and benefit. To start to close this gap, the current article reports on the current use of companion-type robots in care settings, on the effects reported by professional caregivers as well as on the role of psychosocial needs in the acceptance and use of companion-type robots by the elderly. MATERIAL AND METHODS: In the first study, 30 professional caregivers with experience in the use of the robot seal Paro in care settings were interviewed regarding Paro's application and the observed effects on their clients. In the second study, three case examples are presented from an interaction study in which vulnerable elderly persons had the robot dinosaur Pleo at their disposal for a maximum period of 15 days. RESULTS: Paro is used very flexibly in a variety of settings and with a broad range of user groups (study 1). The reported psychosocial effects were mainly positive but short term. The case examples (study 2) show that psychosocial needs can both foster or hinder robot acceptance and use. They also emphasize the important role of caregivers in the interaction between the elderly and emotional robots in the context of eldercare. CONCLUSION: The beneficial and ethical use of companion-type robots in care settings demands a high commitment on the part of the caregivers. Given this prerequisite, emotional robots can be a valuable therapeutic tool.

Assessing capacity to consent to treatment with cholinesterase inhibitors in dementia using a specific and standardized version of the MacArthur Competence Assessment Tool (MacCAT-T).

BACKGROUND: The use of assessment tools has been shown to improve the inter-rater reliability of capacity assessments. However, instrument-based capacity assessments of people with dementia face challenges. In dementia research, measuring capacity with instruments like the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) mostly employ hypothetical treatment vignettes that can overwhelm the abstraction capabilities of people with dementia and are thus not always suitable for this target group. The primary aim of this study was to provide a standardized real informed consent paradigm that enables the dementia-specific properties of capacity to consent to treatment in people with dementia to be identified in a real informed consent process that is both externally valid and ethically justifiable. METHODS: The sample consisted of 53 people with mild to moderate dementia and a group of 133 people without cognitive impairment. Rather than using a hypothetical treatment vignette, we used a standardized version of the MacCAT-T to assess capacity to consent to treatment with cholinesterase inhibitors in people with dementia. Inter-rater reliability, item statistics, and psychometric properties were also investigated. RESULTS: Intraclass correlations (ICCs) (0.951-0.990) indicated high inter-rater reliability of the standardized real informed consent paradigm. In the dementia group, performance on different items of the MacCAT-T varied. Most people with dementia were able to express a treatment choice, and were aware of the need to take a tablet. Further information on the course of the disorder and the benefits and risks of the treatment were less understood, as was comparative reasoning regarding treatment alternatives. CONCLUSION: The standardized real informed consent paradigm enabled us to detect dementia-specific characteristics of patients' capacity to consent to treatment with cholinesterase inhibitors. In order to determine suitable enhanced consent procedures for this treatment, we recommend the consideration of MacCAT-T results on an item level. People with dementia seem to understand only basic information. Our data indicate that one useful strategy to enhance capacity to consent is to reduce attention and memory demands as far as possible.

[Alzheimer's disease from Auguste Deter to the present : Progress, disappointments and open questions]. / Alzheimer-Demenz von Auguste Deter bis heute : Fortschritte, Enttäuschungen und offene Fragen.

AIM: The present article aims to provide a short overview of the discovery history, conceptual development, as well as on current neurobiological and pharmacological research questions in the field of Alzheimer's disease (AD). In view of the long hoped for but so far unachieved therapeutic breakthrough, this also includes a critical reflection of current research paradigms. MATERIAL AND METHODS: Starting from the first case report described by Alois Alzheimer in 1906, the historical impact of his seminal discovery is reconstructed. Neurobiological research paradigms central to AD are discussed with respect to their relevance for modern biomarker-based diagnostic approaches as well as to the development of innovative disease-modifying drug therapies. RESULTS: Originally conceived as a rare presenile form of dementia it was not until the 1970s that AD was granted an orphan disease status. The biomedical deconstruction of senility and the introduction of new research methods enabled the nosological unification of AD with the concept of senile dementia which, in turn led to a global flowering of AD research. In the 1990s the amyloid cascade hypothesis was introduced as the leading research paradigm of AD. In the following years this stimulated the development of a huge variety of innovative biomarker-based diagnostic and disease-modifying pharmacological approaches. CONCLUSION: Against the background of the recent failures of many clinical drug trials, the relevance of the amyloid cascade hypothesis to explain the etiology of sporadic AD is increasingly being questioned. On the one hand, this leaves the question of the central etiological paradigm unresolved and on the other hand it stimulated a debate on alternative etiological models which might lead to fruitful consequences for future research strategies.