Search

Abstract: Improving risk prediction of Alzheimer’s dementia poses challenges to healthcare professionals, patients, and their social environment. Moreover, predictive diagnosis faces limited operationalized clinical recommendations. In this study, we developed manuals for counseling individuals with mild cognitive impairment on their biomarker-based dementia risk prediction; we interviewed 16 participants postcounseling. The interview analysis examines sources of knowledge concerning the decision regarding risk prediction. Subsequently, an interdisciplinary interpretation discusses implications for practice. By focusing on sources of the participants’ knowledge, we identified epistemic authorities, such as (former) medical-related professional background or previous disease experiences. The findings provide information on cues and conversational elements for improving counseling sessions. Sensibly integrated language-based and legal considerations may achieve a targeted and efficient joint decision-making process.

Abstract: Progress in predictive medicine has increased the challenges to navigating complex risk information for patients and healthcare professionals. This contribution investigates how people facing the risk of developing Alzheimer’s dementia perceive risk, what aspects are relevant to their health literacy, and how to promote individual health literacy in predictive medicine. We conducted a qualitative study analyzing narrative interviews, body maps, and sociodemographic data from persons who had undergone early predictive procedures in a memory clinic. We understand the promotion of health literacy as an ethical task in predictive medicine and argue for (1) emphasizing personal resources to promote subjective health literacy, (2) reframing communication and decision-making about disease risk, and (3) teaching skills for value-sensitive, individualized risk communication.

ObjectivesThe main goal of machine learning approaches to classify people into healthy, increased Alzheimer’s disease (AD) risk, and AD is the identification of valuable predictors for valid classification, prediction of conversion, and automatization of the process. While biomarkers from cerebrospinal fluid (CSF) are the best-established predictors for AD, other less invasive, easy-to-assess candidate predictors have been identified. Here, we evaluated the predictive value of such less invasive, predictors separately and in different combinations for classification of healthy controls (HC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and mild AD.MethodsWe evaluated the predictive value of personality scores, geriatric anxiety and depression scores, a resting-state functional magnetic resonance imaging (fMRI) marker (mPerAF), apoliprotein E (ApoE), and CSF markers (tTau, pTau181, Aβ42/40 ratio) separately and in different combinations in multi-class support vector machine classification. Participants (189 HC, 338 SCD, 132 MCI, 74 mild AD) were recruited from the multi-center DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE).ResultsHC were best predicted by a feature set comprised of personality, anxiety, and depression scores, while participants with AD were best predicted by a feature set containing CSF markers. Both feature sets had equally high overall decoding accuracy. However, all assessed feature sets performed relatively poorly in the classification of SCD and MCI.ConclusionOur results highlight that SCD and MCI are heterogeneous groups, pointing out the importance of optimizing their diagnosis criteria. Moreover, CSF biomarkers, personality, depression, and anxiety indicate complementary value for class prediction, which should be followed up on in future studies.Key PointsUsing multi-class support vector machine, we compared the predictive value of well-established versus non-invasive, easy-to-assess candidate variables for classification of participants with healthy cognition, subjective cognitive decline, mild cognitive impairment, and mild Alzheimer’s disease.Personality traits, geriatric anxiety and depression scores, resting-state mPerAF, ApoE genotype, and CSF markers were comparatively evaluated both separately and in different combinations.Predictive accuracy was similarly high for a combination of personality, anxiety and depression scores as for CSF markers.Both established as well as candidate variables performed poorly in classifying SCD and MCI, highlighting heterogenous causes of those cognitive states.CSF biomarkers and extended personality measures show complementary value for class prediction, which should be followed up on in future studies.

Mit modernen Früherkennungsuntersuchungen lässt sich die Alzheimer-Krankheit (Alzheimer’s Disease, AD) lange vor Symptombeginn der Alzheimer-Demenz nachweisen. Patienten fragen immer häufiger nach entsprechenden diagnostischen Verfahren. Der Einsatz von Biomarkern für die Früherkennung der AD ist somit zunehmend klinisch bedeutsam. Dieser Artikel gibt einen Überblick über die derzeitigen prädiktiven Verfahren der Alzheimer-Demenz.

There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona. We investigated whether respective biomarker changes are evident before onset of cognitive impairment. YKL-40; sTREM2; sAXL; sTyro3; MIF; complement factors C1q, C4, and H; ferritin; and ApoE protein were elevated in pre-dementia subjects with pathological levels of tau or other neurodegeneration markers, demonstrating tight interactions between inflammation and accumulating neurodegeneration even before onset of symptoms. Intriguingly, higher levels of ApoE and soluble TAM receptors sAXL and sTyro3 were related to larger brain structure and stable cognitive outcome at follow-up. Our findings indicate a protective mechanism relevant for intervention strategies aiming to regulate neuroinflammation in subjects with no or subjective symptoms but underlying AD pathology profile.

ZusammenfassungDie leichte kognitive Störung („mild cognitive impairment“, MCI) zeichnet sich durch kognitive Einschränkungen bei im Wesentlichen erhaltener Alltagskompetenz aus. MCI ist ein Risikozustand für die Entwicklung einer Demenz und kann ein Prodromalstadium der Demenz bei Alzheimer-Krankheit („Alzheimer’s disease“, AD) sein. Die AD ist durch zerebrale Ablagerungen von Amyloid- und Tau-Aggregaten definiert und kann durch Biomarker für diese Veränderungen in vivo detektiert werden. Durch die Fortschritte in der biomarkerbasierten Früherkennung der AD, ist es möglich zwischen MCI-Patienten mit und ohne AD-Pathologie und somit zwischen Patienten mit einem geringen und einem hohen Risiko für die Entwicklung einer späteren Demenz zu unterscheiden. Für die biomarkerbasierte Früherkennung der AD im MCI-Stadium gibt es bisher in Deutschland keine differenzierten Leitlinienempfehlungen. In dem vorliegenden Artikel werden die Empfehlungen einer europäischen Expertenkonsensuspublikation sowie einer multidisziplinären Arbeitsgruppe der Alzheimer’s Association zum Einsatz von Liquorbiomarkern für die Diagnostik der Alzheimer-Krankheit bei MCI-Patienten zusammengefasst. Sind die klinischen Diagnosekriterien eines MCI anhand der klinischen Untersuchung und neuropsychologischen Testung erfüllt, wird empfohlen weiterführende Diagnostik (Blutuntersuchung, zerebrale Bildgebung) durchzuführen, um die differenzialdiagnostische Einordnung zu präzisieren. Vor der Liquorbiomarkeruntersuchung sollte eine umfassende Beratung zu den Möglichkeiten, Grenzen und Risiken der biomarkerbasierten Früherkennung der AD und der Demenzprädiktion durchgeführt werden. Die Informationen über das individuelle Risiko für eine Demenz können sich bei Patienten und ihren nahestehenden Personen auf das psychische Wohlbefinden und die weitere Lebensplanung auswirken, daher werden klinische Verlaufsuntersuchungen empfohlen.

Background Expanding technologies of early detection of Alzheimer’s disease allow to identify individuals at risk of dementia in early and asymptomatic disease stages. Neuropsychiatric symptoms, such as anxiety and depression, are common in the course of AD and may be clinically observed many years before the onset of significant cognitive symptoms. To date, therapeutic interventions for AD focus on pharmacological and life style modification-based strategies. However, despite good evidence for psychotherapy in late-life depression, evidence for such therapeutic approaches to improve cognitive and emotional well-being and thereby reduce psychological risk factors in the course of AD are sparse. Methods A systematic review was conducted in PUBMED, PsycINFO, Web of Science, and Clinical Trials to summarize the state of evidence on psychotherapeutic and psychoeducational interventions for individuals at risk for Alzheimer’s dementia. Eligible articles needed to apply a manualized and standardized psychotherapeutic or psychoeducational content administered by trained professionals for individuals with subjective cognitive decline or mild cognitive impairment and measure mental health, quality of life or well-being. Results The literature search yielded 32 studies that were included in this narrative summary. The data illustrates heterogeneous therapeutic approaches with mostly small sample sizes and short follow-up monitoring. Strength of evidence from randomized-controlled studies for interventions that may improve mood and well-being is scarce. Qualitative data suggests positive impact on cognitive restructuring, and disease acceptance, including positive effects on quality of life. Specific therapeutic determinants of efficacy have not been identified to date. Conclusions This review underlines the need of specific psychotherapeutic and psychoeducational approaches for individuals at risk of Alzheimer’s dementia, particularly in terms of an early intervention aiming at improving mental health and well-being. One challenge is the modification of psychotherapeutic techniques according to the different stages of cognitive decline in the course of AD, which is needed to be sensitive to the individual needs.

Additional file 1. Search strings.

Introduction: Several recent research studies show high performance of blood biomarkers to identify Alzheimer’s disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed. Methods: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Aß42), amyloid-beta40 (Aß40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed. Results: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Aß42/Aß40 (H(2) = 7.50, p = 0.02) and pTau181/Aß42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Aß42 and an SCD versus MCI difference for Aß42/Aß40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Aß42, Aß40, and NFL concentrations. Conclusion: Plasma pTau181 and NFL, as well as the ratios Aß42/Aß40 and pTau181/Aß42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies.

Expanding technologies of early disease detection allow to identify Alzheimer's disease (AD) long before symptom onset. Hence, patients are increasingly demanding for these diagnostic procedures. Biomarker-based early detection of AD is therefore increasingly important in the clinical work-up. This article gives an overview of predictive procedures in the field of Alzheimer's dementia.Mit modernen Früherkennungsuntersuchungen lässt sich die Alzheimer-Krankheit (Alzheimer’s Disease, AD) lange vor Symptombeginn der Alzheimer-Demenz nachweisen. Patienten fragen immer häufiger nach entsprechenden diagnostischen Verfahren. Der Einsatz von Biomarkern für die Früherkennung der AD ist somit zunehmend klinisch bedeutsam. Dieser Artikel gibt einen Überblick über die derzeitigen prädiktiven Verfahren der Alzheimer-Demenz.

Today, a growing number of individuals with mild cognitive impairment (MCI) wish to assess their risk of developing Alzheimer's disease (AD) dementia. The expectations as well as the effects on quality of life (QoL) in MCI patients and their close others through biomarker-based dementia risk estimation are not well studied.The PreDADQoL project aims at providing empirical data on effects of such prediction on QoL and at developing an ethical and legal framework of biomarker-based dementia risk estimation in MCI.In the empirical study, 100 MCI-patients and their close others will be recruited from two sites (Germany and Spain). They receive standardized counselling on cerebrospinal fluid (CSF) biomarker-based prediction of AD dementia and a risk disclosure based on their AD biomarker status. A mixed methods approach will be applied to assess outcomes.The pilot-study yielded a specification of the research topics and newly developed questionnaires for the main assessment. Within this binational quantitative and qualitative study, data on attitudes and expectations toward AD risk prediction, QoL, risk communication, coping strategies, mental health, lifestyle changes, and healthcare resource utilization will be obtained. Together with the normative part of the project, an empirically informed ethical and legal framework for biomarker-based dementia risk estimation will be developed.The empirical research of the PreDADQoL study together with the ethical and legal considerations and implications will help to improve the process of counselling and risk disclosure and thereby positively affect QoL and health of MCI-patients and their close others in the context of biomarker-based dementia risk estimation.

Mild cognitive impairment (MCI) is characterized by cognitive deficits but essentially preserved competence in activities of daily living. It is a risk factor for the development of dementia and can reflect a prodromal predementia state of Alzheimer's disease (AD). The pathology of AD is defined by cerebral deposition of amyloid-beta-1-42 protein and aggregation of phosphorylated tau protein, which can be identified in vivo by biomarkers for these alterations. As a result of advances in the field of biomarker-based early detection of AD, it is possible to differentiate between MCI patients with and without a pathological AD condition and therefore, between patients with a low and those with a high risk for the development of dementia. At present there are no specific guideline recommendations in Germany for the diagnostic use of biomarkers in predementia detection of AD and for dementia risk assessment in patients with MCI. This article summarizes the current recommendations of a European expert consensus publication and a multidisciplinary working group of the Alzheimer's Association on the clinical application of cerebrospinal fluid (CSF) biomarkers for the diagnostics of AD in patients with MCI. If the clinical diagnostic criteria for MCI are fulfilled according to the medical history and neuropsychological testing, it is recommended to carry out further diagnostics (blood test, brain imaging) in order to more precisely define the differential diagnostic classification. Counseling on the potential benefits, limits and risks of biomarker testing for early AD detection and dementia risk prediction should always precede assessment of CSF biomarkers. Information about the individual risk of developing dementia has potential consequences for the psychological well-being and life planning; therefore, clinical follow-up visits are recommended.

Background: Health literacy (HL) refers to the capacity to access, understand, appraise and apply information for decision-making and acting in health-related matters. In the field of Alzheimer’s disease (AD), expanding technologies of early disease detection, disease course prediction and eventually personalized prevention confront individuals at-risk with increasingly complex information, which demand substantial HL skills. Here we report current findings of HL research in at-risk groups. Methods: Search strings, referring to HL, AD, amyloid and risk, were developed. A systematic review was conducted in PUBMED, Cochrane Library, PsycINFO, and Web of Science to summarize the state of evidence on HL in at-risk individuals for Alzheimer’s dementia. Eligible articles needed to employ a validated tool for HL, mention the concept or one dimension (access, understand, appraise and apply information for decision-making and acting). Results: 26 quantitative and 9 qualitative studies addressing at least one dimension of HL were included. Overall, there is evidence for a wish to gain knowledge about the own brain status and risk of dementia. Psychological distress may occur and the subjective benefit-risk estimation may be modified after risk disclosure. Effects on lifestyle and planning may occur. Overall understanding and appraisal of information related to AD risk seem variable with several impacting factors. In mild cognitive impairment (MCI) basic HL skill seem to be affected by cognitive dysfunction. Conclusions: Systematic assessment of HL in at-risk population for AD is sparse. Findings indicate the paramount importance of adequate communication with persons at risk, being sensitive to individual needs and preferences. Substantial research needs were identified.

This case report deals with a 25-year-old woman who suffered from a long-term borderline personality disorder and from acute suicidal tendencies, including the intentional consumption of poisonous plants. When questioned during her self-referral to the psychiatric emergency department, she denied any suicide attempt or consumption of poisonous agents. Due to her medical history, her admission was followed by an intensive medical observation. During this observation period, the patient suffered an episode of acute respiratory insufficiency, which was followed by cardiac arrest. All resuscitation attempts were futile. Due to the unexplained nature of her death, the case was referred to the criminal investigation department. All findings of the routine systematic toxicological analysis of the patient’s blood sample, including immunochemical examinations and a high-performance liquid chromatography general unknown screening for drugs, were in accordance with the patient’s medication regimen and did not indicate a lethal overdose of any drug. During the analytical examinations, the deceased’s mother informed the psychiatric outpatient service of having found yew leaves in her daughter’s clothes and at her flat. The liquid chromatography--tandem mass spectrometry target analysis for yew pseudo-alkaloids (taxine B/isotaxine B) yielded a combined concentration of 110 µg/L. No autopsy was performed, because no criminality was suspected. In conclusion, it seems most plausible to conclude that the patient died of yew intoxication.

Objective Numerous studies suggest that health literacy (HL) plays a crucial role in maintaining and improving individual health. Empirical findings highlight the relation between levels of a person's HL and her/his clinical outcome. To date, the role of HL in persons at-risk for psychosis has not been systematically reviewed. Methods We conducted a systematic review using a mixed-methods approach to analyse a variety of study types. Peer-reviewed publications were systematically searched in PUBMED, Cochrane Library, PsycINFO and Web of Science. Results The search string returned 10587 publications. After screening, 15 quantitative, four qualitative studies and two reviews were included. Only one study assessed HL as primary outcome, assessing knowledge and beliefs about psychosis among the general population. In the other studies, sub-dimensions of HL were investigated. None of the publications operationalized HL or it's sub-dimensions with a validated measure. Conclusions A lack of understanding of their condition, and fear of stigmatization, were associated with a delay in help-seeking among people with clinical-high-risk state for psychosis. Family members, school personnel, general practitioners and the internet play a crucial role in the HL process. Considerable barriers in obtaining adequate specialist support emphasize the urgent need of a "HL environment" for persons at risk for psychosis.

Background Numerous studies suggest that health literacy (HL) plays a crucial role in maintaining and improving individual health. Furthermore, empirical findings highlight the relation between levels of a person’s HL and clinical outcomes. So far, there are no reviews, which investigate HL in individuals at-risk for psychosis. The aim of the current review is to assess how individuals at risk of developing a first episode of psychosis gain access to, understand, evaluate and apply risk-related health information. Methods A mixed-methods approach was used to analyze and synthesize a variety of study types including qualitative and quantitative studies. Search strategy, screening and data selection have been carried out according to the PRISMA criteria. The systematic search was applied on peer-reviewed literature in PUBMED, Cochrane Library, PsycINFO and Web of Science. Studies were included if participants met clinical high risk criteria (CHR), including the basic symptom criterion (BS) and the ultra-high risk (UHR) criteria. The UHR criteria comprise the attenuated psychotic symptom criterion (APS), the brief limited psychotic symptom criterion (BLIPS) and the genetic risk and functional decline criterion (GRDP) Furthermore, studies must have used validated HL measures or any operationalization of the HL’s subdimensions (access, understanding, appraisal, decision-making or action) as a primary outcome. A third inclusion criterion comprised that the concept of HL or one of the four dimensions was mentioned in title or abstract. Data extraction and synthesis was implemented according to existing recommendations for appraising evidence from different study types. The quality of the included studies was evaluated and related to the study results. Results The search string returned 10587 papers. After data extraction 15 quantitative as well as 4 qualitative studies and 3 reviews were included. The Quality assessment evaluated 12 publications as “good”, 9 as “fair” and one paper as “poor”. Only one of the studies assessed HL with as primary outcome. In the other studies, the five different subdimensions of HL were investigated as a secondary outcome respectively mentioned in the paper. “Gaining Access” was examined in 18 of the 22 studies. “Understanding” has been assessed in 7 publications. “Appraise” was examined in 9 studies. “Apply decision making” and “Apply health behavior” were investigated in 1 of 8 studies. Since none of the included publications operationalized neither HL nor the subdimensions of HL with a validated measure, no explicit influencing factors could be found. Discussion Quantitative and qualitative evidence indicates that subjects at-risk for psychosis describe a lack of understanding about their state and fear stigmatization that might lead to dysfunctional coping strategies, such as ignoring and hiding symptoms. Affected subjects are eager to be informed about their condition and describe favoured channels for obtaining information. The internet, family members, school personnel and GP’s play a crucial role in gain access to, understand, evaluate and apply risk-related health information. The results clearly highlight that more research should be dedicated to HL in individuals at risk of developing a psychosis. Further studies should explore the relation between HL and clinical outcomes in this target population by assessing the underlining constructs with validated tools.

The WU-virus (WUV), a novel polyomavirus, has recently been recovered from respiratory tract samples. Within a study collective of children with severe lower respiratory tract disease, 3% of the patients tested WUV positive. Viral loads ranged from 5 × 102 copies/ml to 1 × 104 copies/ml. The WUV genome-positive patients did not display specific clinical or radiological characteristics to be distinguished from other respiratory tract infections.