Development of a Cognitive Training Support Programme for prevention of dementia and cognitive decline in at-risk older adults

BackgroundEvidence for the beneficial effects of cognitive training on cognitive function and daily living activities is inconclusive. Variable study quality and design does not allow for robust comparisons/meta-analyses of different cognitive training programmes. Fairly low adherence to extended cognitive training interventions in clinical trials has been reported.AimsThe aim of further developing a Cognitive Training Support Programme (CTSP) is to supplement the Computerised Cognitive Training (CCT) intervention component of the multimodal Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), which is adapted to different cultural, regional and economic settings within the Word-Wide FINGERS (WW-FINGERS) Network. The main objectives are to improve adherence to cognitive training through a behaviour change framework and provide information about cognitive stimulation, social engagement and lifestyle risk factors for dementia.MethodsSix CTSP sessions were re-designed covering topics including (1) CCT instructions and tasks, (2) Cognitive domains: episodic memory, executive function and processing speed, (3) Successful ageing and compensatory strategies, (4) Cognitive stimulation and engagement, (5) Wellbeing factors affecting cognition (e.g., sleep and mood), (6) Sensory factors. Session content will be related to everyday life, with participant reflection and behaviour change techniques incorporated, e.g., strategies, goal-setting, active planning to enhance motivation, and adherence to the CCT and in relevant lifestyle changes.ConclusionsThrough interactive presentations promoting brain health, the programme provides for personal reflection that may enhance capability, opportunity and motivation for behaviour change. This will support adherence to the CCT within multidomain intervention trials. Efficacy of the programme will be evaluated through participant feedback and adherence metrics

Insulin levels are decreased in the cerebrospinal fluid of women with prodomal Alzheimer's disease

Previous studies have failed to reach consensus on insulin levels in cerebrospinal fluid of Alzheimer's disease (AD) patients and on its relation to pathological features. We performed a new analysis in patients at different stages of AD, and investigated the relationship of insulin levels with biochemical disease markers and with cognitive score. We included 99 patients from our Memory Clinic (Karolinska University Hospital, Sweden), including: 27 patients with mild AD, 13 that progressed from mild cognitive impairment (MCI) to AD in two years time, 26 with MCI stable after two years, and 33 with subjective cognitive impairment. Insulin was significantly decreased in the cerebrospinal fluid of both women and men with mild AD. Insulin deficits were seen in women belonging to both MCI groups, suggesting that this occurs earlier than in men. Insulin was positively associated with amyloid-β 1-42 (Aβ1-42) levels and cognitive score. Furthermore, total-tau/(Aβ1-42*insulin) ratio showed strikingly better sensitivity and specificity than the total-tau/Aβ1-42 ratio for early AD diagnosis in women

Education-Based Cutoffs for Cognitive Screening of Alzheimer’s Disease

Introduction: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. Methods: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. Results: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. Conclusions: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.Peer reviewe

Cognitive Performance at Time of AD Diagnosis : A Clinically Augmented Register-Based Study

We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer's disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010-2013 (aged 60-81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.Peer reviewe

Association Between Cognition, Health Related Quality of Life, and Costs in a Population at Risk for Cognitive Decline

Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition. Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline. Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n= 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms. Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.Peer reviewe

A stepwise approach towards diagnostic workup in dementia using online cognitive tools

AbstractBackgroundDementia affects more and more people worldwide. Unfortunately, only half of dementia cases are well recognized. This indicates a need for both efficient and tailored tools for diagnosis. To improve the number of correctly diagnosed patients while retaining cost‐effectiveness, we study a stepwise data‐driven approach for the diagnostic workup. By using the online cognitive test tool cCOG [1] as prescreener, we aim to select the right diagnostic workup for each patient.MethodsWe included 710 subjects from three memory clinic cohorts (PredictND, VPH‐DARE and Amsterdam dementia cohort) with different types of dementia and subjective cognitive decline (SCD). All patients performed a neuropsychological (NP) test battery (consisting of MMSE, RAVLT, TMT‐A and B and Animal Fluency) and had MRI of the brain. A subset of 214 subjects additionally performed cCOG. To verify results we imputed missing cCOG based on corresponding NP tests [1]. From MRI, multiple imaging biomarkers were defined [2]. We tested a stepwise diagnostic approach, starting with screening using cCOG, then if needed testing with NP test battery and MRI, using the Disease State Index (DSI) classifier [2]. At each step patients were selected for the next step based on DSI model's confidence (Figure 1).ResultsThe stepwise approach was as accurate as performing all tests in every patient (Table 1), but it reduced the number of tests done especially in SCD patients considerably, with NP in only 57% and MRI in 38% (Table 2). This was also reflected in reduced cost per patient in typical memory clinic population (from estimated 510 € to 238‐243 €). For dementia patients the reduction in number of tests and costs was smaller.ConclusionThis study suggest that using a stepwise approach, applying online cognitive tests as prescreening at home, can reduce the number of patient visits to clinic and costs. The results were as accurate as with the standard traditional work‐up. Online cognitive testing is therefore a promising tool to funnel the patient flow to memory clinics, also in times of social distancing. References: [1] Rhodius‐Meester, H.F.M. et al. Alzheimers Dement 2020 Aug25;12(1) [2] Bruun, M. et al. Alzheimers Dement 2018 Aug17;10

Neuropsychology/computerized neuropsychological assessment

AbstractBackgroundDifferential diagnostics in dementia is challenging. To date, the basic assessment still includes imaging of the brain and cognitive testing with pen and paper. Web‐based cognitive tests however hold potential for standardized and low‐cost screening in clinical workup. How they perform when combined with imaging of the brain is unknown. We therefore evaluated the accuracy of a new web‐based cognitive battery (Muistikko [1]) detecting different types of dementia, when combined with brain MRI, and compared this to traditional cognitive testing and MRI.MethodWe included 229 subjects from two memory clinic cohorts (PredictND and VPH‐DARE), consisting of 188 controls, 29 patients with Alzheimer's dementia (AD), 7 with frontotemporal dementia (FTD) and 5 with vascular dementia (VaD) (Table 1). All patients performed a traditional cognitive test battery (consisting of MMSE, RAVLT, TMT‐A and B, Animal Fluency), web‐based cognitive testing and had MRI of the brain. Although Muistikko is composed of seven subtasks, only global cognitive score (GCS) was used as defined in [1]. From MRI, multiple imaging biomarkers were defined [2]. Disease‐state index classifier was developed from the predictors [2]. Cross‐validation was used to calculate balanced accuracy (BACC; average of sensitivities for each diagnostic group). Given the class imbalance, we also calculated prevalence corrected accuracy (PACC).ResultBACC was 66 % and PACC 64% when using the traditional cognitive test battery + MRI. Both BACC and PAC were 69 % when using the web‐based cognitive testing + MRI (Table 2). Of note, since we compare four diagnostic groups, BACC by guessing would be 25%.ConclusionThis study shows that combining web‐based cognitive tests with MRI data results in high accuracy when separating different types of dementia. The results were comparable with the standard traditional work‐up. Web‐based cognitive testing is therefore a promising tool to support the clinician in the daily challenge of differential diagnostics, especially when combined with MRI data. References: [1] Paajanen, S. et al. Detecting cognitive disorders using Muistikko web‐based cognitive test battery. Alzheimer's & Dementia 13(7):Supplement,P234‐P235,2017 [2] Bruun, M. et al. Evaluating combinations of diagnostic tests to discriminate different dementia types. Alzheimers Dement 2018 Aug17;10:509‐51

COVID-19 pandemic and mortality in nursing homes across USA and Europe up to October 2021

Purpose We compared the prevalence of COVID-19 and related mortality in nursing homes (NHs) in 14 countries until October 2021. We explored the relationship between COVID-19 mortality in NHs with the average size of NHs and with the COVID-19 deaths at a population level. Methods The total number of COVID-19 cases and COVID-19-related deaths in all NHs as well as the total number of NHs and NH beds were provided by representatives of 14 countries. The population level respective figures in each country were provided up to October 2021. Results There was a wide variation in prevalence of COVID-19 cases and deaths between countries. We observed a significant correlation between COVID-19 deaths in NHs and that of the total population and between the mean size of NHs and COVID-19 deaths. Conclusion Side-by-side comparisons between countries allow international sharing of good practice to better enable future pandemic preparedness.Peer reviewe

COVID-19 pandemic and mortality in nursing homes across USA and Europe up to October 2021

Purpose We compared the prevalence of COVID-19 and related mortality in nursing homes (NHs) in 14 countries until October 2021. We explored the relationship between COVID-19 mortality in NHs with the average size of NHs and with the COVID-19 deaths at a population level. Methods The total number of COVID-19 cases and COVID-19-related deaths in all NHs as well as the total number of NHs and NH beds were provided by representatives of 14 countries. The population level respective figures in each country were provided up to October 2021. Results There was a wide variation in prevalence of COVID-19 cases and deaths between countries. We observed a significant correlation between COVID-19 deaths in NHs and that of the total population and between the mean size of NHs and COVID-19 deaths. Conclusion Side-by-side comparisons between countries allow international sharing of good practice to better enable future pandemic preparedness.Peer reviewe