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Background A high percentage of patients with cancer experience cognitive impairment after cancer treatment, resulting in a decreased health-related quality of life and difficulty returning to work. Consequently, there is a need for effective treatment options to improve cognitive functioning in these patients. In a healthy aging population, multidomain web-based lifestyle interventions have been found to be effective in preventing cognitive decline and improving cognitive functioning. Objective This study aims to investigate the feasibility and effectiveness of the web-based lifestyle intervention Mijn Fitte Brein (My Fit Brain [MFB]) on cognitive functioning in patients with cancer returning to work. Methods The study consists of a feasibility study (N=10), followed by a randomized controlled trial (RCT; N=220). Patients will be recruited by their occupational physicians after their return to work following cancer treatment. Mijn Fitte Brein is organized into 4-week cycles in which patients set a lifestyle goal using the Goal Attainment Scale, receive weekly tips and support, and finally evaluate whether they succeeded in achieving this goal. Lifestyle goals are based on 6 domains: physical exercise, diet, sleep, stress, alcohol use, and smoking. In the feasibility study, data on user experience (structured interview) and usability, assessed with the Post-Study System Usability Scale, will be collected and used to optimize Mijn Fitte Brein. In the RCT, patients will be randomized 1:1 between an intervention group and a control group. Patients will be assessed at baseline, 3 months, and 6 months. The primary outcome measure is subjective cognitive functioning, assessed with the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog). Secondary outcome measures are lifestyle, objective cognitive functioning, and work and psychosocial factors. Results Recruitment for the feasibility study has started in February 2020. As of July 2020, however, no patients have been enrolled (due to COVID-19 restrictions). The findings of the feasibility study will be used to optimize the Mijn Fitte Brein intervention. Enrollment for the RCT will continue when possible. The feasibility study will take 6 months (including making adjustments to the intervention), and the RCT will take 2 years. The final results are expected in 2024. The results of the feasibility study and the RCT will be published in peer-reviewed journals. Conclusions This is the first time the feasibility and efficacy of a multidomain web-based lifestyle intervention will be studied in patients with cancer. If Mijn Fitte Brein is found to be effective in decreasing cognitive complaints in these patients returning to work, it will be a promising treatment option because of being both affordable and accessible. Trial Registration Netherlands Trial Register NL8407; https://www.trialregister.nl/trial/8407 International Registered Report Identifier (IRRID) DERR1-10.2196/22670

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's AssociationIntroduction: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. Methods: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. Results: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. Discussion: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.

ObjectiveTo investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD).MethodsWe classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD.ResultsFifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A–T–N–), 27% (n = 186) had non-AD pathologic change (A–T–N+, A–T+N–, A–T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T–N–, A+T–N+, A+T+N–, A+T+N+). ATN profiles were unevenly distributed, with A–T+N+, A+T–N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A–T–N–, participants in A+ profiles had a higher risk of dementia with a dose–response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition.ConclusionsAmong individuals presenting with SCD at a memory clinic, those with a biomarker profile A–T+N+, A+T–N–, A+T+N–, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A–T–N– individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.

Purpose To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. Methods We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [18F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BPND) and standardized uptake value ratio (SUVr50–70) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BPND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen’s kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19–0.29 BPND/1.28–1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. Results As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BPND thresholds (range kappa 0.65–0.70 versus 0.60–0.63). All thresholds predicted memory decline (range beta − 0.29 to − 0.21, all p p for trend Conclusion We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. Therefore, in case a binary classification is required, we suggest using a relatively low threshold which includes grey zone amyloid pathology.

Background We aimed to describe the Subjective Cognitive Impairment Cohort (SCIENCe) study design, to cross-sectionally describe participant characteristics, and to evaluate the SCD-plus criteria. Methods The SCIENCe is a prospective cohort study of subjective cognitive decline (SCD) patients. Participants undergo extensive assessment, including cerebrospinal fluid collection and optional amyloid positron emission tomography scan, with annual follow-up. The primary outcome measure is clinical progression. Results Cross-sectional evaluation of the first 151 participants (age 64 ± 8, 44% female, Mini-Mental State Examination 29 ± 2) showed that 28 (25%) had preclinical Alzheimer’s disease (AD) (amyloid status available n = 114 (75%)), 58 (38%) had subthreshold psychiatry, and 65 (43%) had neither. More severe subjective complaints were associated with worse objective performance. The SCD-plus criteria age ≥ 60 (OR 7.7 (95% CI 1.7–38.9)) and apolipoprotein E (genotype) e4 (OR 4.8 (95% CI 1.6–15.0)) were associated with preclinical AD. Conclusions The SCIENCe study confirms that SCD is a heterogeneous group, with preclinical AD and subthreshold psychiatric features. We found a number of SCD-plus criteria to be associated with preclinical AD. Further inclusion and follow-up will address important questions related to SCD. Electronic supplementary material The online version of this article (10.1186/s13195-018-0390-y) contains supplementary material, which is available to authorized users.

Introduction Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression. Methods We included 674 patients with SCD (46% female, 64 ± 9 years, Mini–Mental State Examination 28 ± 2) from three memory clinic cohorts. A multivariate model based on the Disease State Index classifier incorporated the available baseline tests to predict progression to MCI or dementia over time. We developed and internally validated the model in one cohort and externally validated it in the other cohorts. Results After 2.9 ± 2.0 years, 151(22%) patients showed clinical progression. Overall performance of the classifier when combining cognitive tests, magnetic resonance imagining, and cerebrospinal fluid showed a balanced accuracy of 74.0 ± 5.5, with high negative predictive value (93.3 ± 2.8). Discussion We found that a combination of diagnostic tests helps to identify individuals at risk of progression. The classifier had particularly good accuracy in identifying patients who remained stable.

We examined the relationships between amyloid-β PET and concurrent and longitudinal cognitive performance in 107 cognitively normal individuals with subjective cognitive decline (age: 64 ± 8 years, 44% female, Mini-Mental State Examination score 29 ± 1). All underwent 90-minute dynamic [ 18 F]florbetapir PET scanning and longitudinal neuropsychological tests with a mean follow-up of 3.4 ± 3.0 years. Receptor parametric mapping was used to calculate [ 18 F]florbetapir binding potential (BP ND ), and we performed linear mixed models to assess the relationships between global [ 18 F]florbetapir BP ND and neuropsychological performance. Higher [ 18 F]florbetapir BP ND was related to lower concurrent Mini-Mental State Examination (β ± SE: −1.69 ± 0.63 p < 0.01) and to steeper rate of decline on tasks capturing memory (Rey Auditory Verbal Learning Task immediate [β ± SE −1.81 ± 0.81, p < 0.05] and delayed recall [β ± SE −1.19 ± 0.34, p < 0.01]), attention/executive functions (Stroop II [color] [β ± SE −0.02 ± 0.01, p < 0.05], Stroop III [word-color] [β ± SE −0.03 ± 0.02, p < 0.05]), and language (category fluency [β ± SE −0.04 ± 0.01, p < 0.01]). These findings suggest that higher amyloid-β load in cognitively normal individuals with subjective cognitive decline from a memory clinic is associated with lower concurrent global cognition and with faster rate of decline in a variety of cognitive domains.

Background Amyloid pathology is the pathological hallmark in Alzheimer’s disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline. Methods From December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [18F]flutemetamol. In addition, the twin cohort underwent lumbar puncture for cerebrospinal fluid collection, buccal cell collection, magnetoencephalography, optical coherence tomography, and retinal imaging. Results We included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants (22%) had an abnormal amyloid PET scan. Conclusions A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive decline. Electronic supplementary material The online version of this article (10.1186/s13195-018-0406-7) contains supplementary material, which is available to authorized users.

Introduction Individuals with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease and could benefit from a prevention strategy targeting lifestyle factors. Making a program available through the Internet gives a widespread reach at low cost, but suboptimal adherence is a major threat to effectiveness. As a first step in developing an online lifestyle program (OLP), we aimed to identify factors that are barriers and/or facilitators for the use of an OLP in individuals with SCD in three European countries. Methods As part of the Euro-SCD project, SCD subjects were recruited at memory clinics in the Netherlands, Germany, and Spain. We combined quantitative and qualitative methods, using a mixed methods approach. We conducted an online 18-item survey on the preferences of SCD patients for an OLP (N = 238). In addition, we held semi-structured interviews (N = 22) to gain in-depth understanding of factors acting as a facilitator and/or barrier for intended use of an OLP. Audio recordings were transcribed verbatim. Content analysis was performed. Results One hundred seventy-six individuals completed the survey (response rate 74%). Almost all participants regularly use the Internet (97%). Participants reported trustworthiness (93%), user-friendliness (91%), and up-to-date information (88%) as main facilitators, whereas having contact with other users (26%), needing an account (21%), and assignments (16%) were reported as barriers. Barriers differed slightly between countries, but facilitators were largely similar. In-depth interviews revealed that both program characteristics (e.g., trustworthiness, user-friendliness, and personalization) and personal factors (e.g., expectancy to receive negative feedback) are likely to influence the intended use of an OLP. Discussion Involving users provided in-depth understanding of factors associated with the intended use of an OLP for brain health. Both program characteristics and personal factors are likely to influence the use of an OLP. Based on this input from the end-users, we will develop an OLP for individuals with SCD., Highlights • Almost all participants believe that healthy lifestyle contributes to brain health. • Almost all participants use the Internet daily, on all types of devices. • Barriers or facilitators can be program characteristics as well as personal factors. • Trustworthiness, user-friendliness, and personalization are important facilitators. • One online lifestyle program for different European countries seems feasible.