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Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.Objective: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.Design, Setting, and Participants: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Exposures: Alzheimer disease biomarkers detected on PET or in CSF.Main Outcomes and Measures: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Results: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).Conclusions and Relevance: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

Clinical reasoning and research in modern geriatrics often prioritises the disease concept. This is understandable as it has brought impressive advances in medicine (e.g. antibiotics, vaccines, successful cancer treatment and many effective surgeries). However, so far the disease framework has not succeeded in getting us to root causes of many age-related chronic diseases (e.g. Alzheimer’s disease, diabetes, osteoarthritis). Moreover, in aging and disease constructs alone fail to explain the variability in illness presentations. Therefore, we propose to apply the underused illness concept in a new way by reconsidering the importance of common symptoms in the form of a dynamic network of symptoms as a complementary framework. We show that concepts and methods of complex system thinking now enable to fruitfully monitor and analyse the multiple interactions between symptoms in such in networks, offering new routes for prognosis and treatment. Moreover, close attention to the symptoms that bother older persons may also improve weighing the therapeutic objectives of well-being and survival and aligning treatment targets with the patients’ priorities.

Additional file 1.

Purpose The Quality of Life Alzheimer’s Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available. Methods Different statistical models to estimate utility directly, or responses to individual EQ-5D questions (response mapping) from QoL-AD, were trialled for patient-rated and proxy-rated questionnaires. Model performance was assessed by root mean square error and mean absolute error. Results The response model using multinomial regression including age and sex, performed best in both the estimation dataset and an independent dataset. Conclusions The recommended mapping algorithm allows researchers for the first time to estimate EQ-5D values from QoL-AD data, enabling cost-utility analyses using datasets where the QoL-AD but no utility measures were collected.

Objective To develop survival prediction tables to inform physicians and patients about survival probabilities after the diagnosis of dementia and to determine whether survival after dementia diagnosis can be predicted with good accuracy. Methods We conducted a nationwide registry-linkage study including 829 health centers, i.e., all memory clinics and ≈75% of primary care facilities, across Sweden. Data including cognitive function from 50,076 people with incident dementia diagnoses ≥65 years of age and registered with the Swedish Dementia Register in 2007 to 2015 were used, with a maximum follow-up of 9.7 years for survival until 2016. Sociodemographic factors, comorbidity burden, medication use, and dates of death were obtained from nationwide registries. Cox proportional hazards regression models were used to create tables depicting 3-year survival probabilities for different risk factor profiles. Results By August 2016, 20,828 (41.6%) patients in our cohort had died. Median survival time from diagnosis of dementia was 5.1 (interquartile range 2.9–8.0) years for women and 4.3 (interquartile range 2.3–7.0) years for men. Predictors of mortality were higher age, male sex, increased comorbidity burden and lower cognitive function at diagnosis, a diagnosis of non-Alzheimer dementia, living alone, and using more medications. The developed prediction tables yielded c indexes of 0.70 (95% confidence interval [CI] 0.69–0.71) to 0.72 (95% CI 0.71–0.73) and showed good calibration. Conclusions Three-year survival after dementia diagnosis can be predicted with good accuracy. The survival prediction tables developed in this study may aid clinicians and patients in shared decision-making and advance care planning.

Background Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI. Methods/design This randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme. Discussion The results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI. Trial registration ClinicalTrials.gov NCT02913053

Table S1. Unadjusted EQ-5D summary scores by geriatric condition. Table S2. Age and sex adjusted EQ-5D summary scores by sociodemographic characteristics. (DOC 111Â kb)

Background As populations age, chronic geriatric conditions linked to progressive organ failure jeopardize health-related quality of life (HRQoL). Thus, this research assessed the validity and applicability of the EQ-5D (a common HRQoL instrument) across four major chronic geriatric conditions: hearing issues, joint damage, urinary incontinence, or dizziness with falls. Methods The study sample comprised 25,637 community-dwelling persons aged 65 years and older residing in the Netherlands (Data source: TOPICS-MDS, www.topics-mds.eu). Floor and ceiling effects were examined. To assess convergent validity, random effects meta-correlations (Spearman’s rho) were derived between individual EQ-5D domains and related survey items. To further examine construct validity, the association between sociodemographic characteristics and EQ-5D summary scores were assessed using linear mixed models. Outcomes were compared to the overall study population as well as a ‘healthy’ subgroup reporting no major chronic conditions. Results Whereas ceiling effects were observed in the overall study population and the ‘healthy’ subgroup, such was not the case in the geriatric condition subgroups. The majority of hypotheses regarding correlations between survey items and sociodemographic associations were supported. EQ-5D summary scores were lower in respondents who were older, female, widowed/single, lower educated, and living alone. Increasing co-morbidity had a clear negative effect on EQ-5D scores. Conclusion This study supported the construct validity of the EQ-5D across four major geriatric conditions. For older persons who are generally healthy, i.e. reporting few to no chronic conditions, the EQ-5D confers poor discriminative ability due to ceiling effects. Although the overall dataset initially suggested poor discriminative ability for the EQ-5D, such was not the case within subgroups presenting with major geriatric conditions. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0616-x) contains supplementary material, which is available to authorized users.

Contains fulltext : 165927.pdf (Publisher’s version ) (Open Access) BACKGROUND: Our labor force is aging, but aged workers are not yet coached on how to stay cognitively fit for the job. OBJECTIVE: In this study, we tested whether a self-motivated, complex eHealth intervention could improve multiple health-related behaviors that are associated with cognitive aging among working Dutch adults. METHODS: This quasi-experimental prospective study with a pre-post design was conducted with employees of Dutch medium to large companies. All employees with Internet access, a good understanding of the Dutch language, and who provided digital informed consent were eligible to participate. In total, 2972 participants (2110/2972, 71.11% females) with a mean (standard deviation, SD) age of 51.8 (SD 12.9) years were recruited; 2305 became active users of the intervention, and 173 completed the 1-year follow-up. This self-motivated eHealth lifestyle intervention stimulates participants to set personally relevant, monthly health behavior change goals using Goal Attainment Scaling and to realize these goals by implementing behavior change techniques grounded in behavior change theory. The primary outcomes were the goal-setting success rate and the change in overall lifestyle score from baseline to the 1-year follow-up; the score was based on physical activity, diet, smoking, alcohol, sleep, and stress scores. The secondary outcomes were the changes in body weight, body mass index, specific lifestyle characteristics, and website usage. RESULTS: A total of 1212 participants set 2620 behavior change goals; 392 participants assessed 1089 (1089/2288, 47.59%) goals and successfully achieved 422 (422/1089, 38.75%) of these goals. Among the goal-setting participants in follow-up, this led to a +0.81-point improvement (95% CI 0.49-1.13, P

memory performance in drug-na€ive mild AD patients (MMSE 20-26 and MMSE 20), indicating that Souvenaid is efficacious in the early phases of AD. The ’LipiDiDiet’ study 2 is one of the first RCTs in prodromal AD, investigating the effects of Souvenaid on cognition.Methods: The LipiDiDiet study is an ongoing 24-month, double-blind, parallel-group RCT investigating the effects of Souvenaid in 300 prodromal AD subjects (criteria Dubois, 2007). Subjects are randomly assigned to Souvenaid or an iso-caloric control product. Primary outcome measure is cognitive functioning, assessed by a modified version of the Neuropsychological Test Battery (Harrison, 2007). Secondary outcome measures include progression to AD, cognitive performance, functional abilities (ADCS-ADL), depression (MADRS), MRI atrophy rate, plasma and CSF biomarkers, safety, tolerance and nutritional parameters. Main study outcomes are assessed at baseline and after 6, 12 and 24 months of intervention. Baseline characteristics of the study population are analyzed.Results: Preliminary analysis of baseline data from 213 randomized subjects (47.9% male, enrolled until July 2012) showed that subjects had a mean age of 71.866.9 years, MMSE score of 26.662.0 and ADAS-cog score of 19.767.8. Baseline biomarker data from a subsample of subjects (n1⁄422) showed a CSF b-amyloid 1-42/ 1-40x10 ratio of 1.8960.71, CSF total tau of 465.56269.6 pg/ml, CSF phosphorylated tau of 74.5635.6 pg/ml and MTA score of 1.6461.00 (MRI evidence for medial temporal lobe atrophy). Last subject randomized in the study is expected early 2013. Therefore, baseline characteristics of the total study population will be presented at the conference. Conclusions: Baseline characteristics of the study population included in the LipiDiDiet study so far are as expected for subjects with prodromal AD.