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Abstract Background Both memory clinic professionals and patients see value in digital tools, yet these hardly find their way to clinical practice. We explored the usability of a digital tool to support the diagnostic work-up in daily memory clinic practice. We evaluated four modules that integrate multi-modal patient data (1.cognitive test; cCOG, and 2. MRI quantification; cMRI) into useful diagnostic information for clinicians (3. cDSI) and understandable and personalized information for patients (4. patient report). Methods We conducted a mixed-methods study in five Dutch memory clinics. Fourteen clinicians (11 geriatric specialists/residents, two neurologists, one nurse practitioner) were invited to integrate the tool into routine care with 43 new memory clinic patients. We evaluated usability and user experiences through quantitative data from questionnaires (patients, care partners, clinicians), enriched with thematically analyzed qualitative data from interviews (clinicians). Results We observed wide variation in tool use among clinicians. Our core findings were that clinicians: 1) were mainly positive about the patient report, since it contributes to patient-centered and personalized communication. This was endorsed by patients and care partners, who indicated that the patient report was useful and understandable and helped them to better understand their diagnosis, 2) considered the tool acceptable in addition to their own clinical competence, 3) indicated that the usefulness of the tool depended on the patient population and purpose of the diagnostic process, 4) addressed facilitators (ease of use, practice makes perfect) and barriers (high workload, lack of experience, data unavailability). Conclusion This multicenter usability study revealed a willingness to adopt a digital tool to support the diagnostic process in memory clinics. Clinicians, patients, and care partners appreciated the personalized diagnostic report. More attention to education and training of clinicians is needed to utilize the full functionality of the tool and foster implementation in actual daily practice. These findings provide an important step towards a lasting adoption of digital tools in memory clinic practice.

Summary: Hypertension and orthostatic hypotension (OH) frequently coexist in the older population, both stemming from impaired blood pressure (BP) regulation. Managing hypertension in patients with OH presents a significant clinical challenge, particularly in frail older adults who are also prone to falls. Hypertension treatment is often suboptimal in this population due to concerns over the potential increased risk of falls associated with treatment. However, current clinical guidelines provide limited guidance on managing this complex issue. This review explores the pathophysiology of hypertension and OH, reviews existing guidelines, and examines the evidence surrounding hypertension management in patients with OH. Additionally, we provide an overview of research focused on frail older adults and offer expert-opinion-based recommendations for the management of hypertension and OH in routine clinical practice.

Abstract Many women experience impairment in cognitive function during perimenopause. These symptoms are often not attributed to perimenopause by women themselves, by family and friends, or by healthcare professionals. In this article, we present a case in which perimenopausal complaints were attributed to early dementia and discuss mechanisms contributing to the low level of awareness of perimenopausal symptoms amongst patients and clinicians. Stigma amongst women and healthcare professionals impairs the recognition of perimenopausal complaints, and consideration of treatment options by clinicians. We advocate raising awareness in patients and physicians with more education, and the incorporation of potential menopause-related symptoms in general clinical guidelines.

Abstract Background Prior studies suggest a changing association between blood pressure (BP) and cognition with aging, however work in the oldest-old has yielded ambiguous results. Potentially, these mixed results can be explained by modifying factors. The aim of this study was to establish whether physical, vascular or brain pathology markers that describe a state of increased vulnerability, affect the association between BP and cognition in the oldest-old. Results may influence clinicians’ decisions regarding the use of antihypertensives in this age group. Methods We included 122 individuals (84 without cognitive impairment and 38 with cognitive impairment) from the EMIF-AD 90 + Study (mean age 92.4 years). First, we tested cross-sectional associations of systolic and diastolic BP with a cognitive composite score. Second, we tested whether these associations were modified by physical markers (waist circumference, muscle mass, gait speed and handgrip strength), vascular markers (history of cardiac disease, carotid intima media thickness as a proxy for atherosclerosis and carotid distensibility coefficient as a proxy for arterial stiffness) or brain pathology markers (white matter hyperintensities and cortical thickness). Results In the total sample, there was no association between BP and cognition, however, waist circumference modified this association (p-value for interaction with systolic BP: 0.03, with diastolic BP: 0.01). In individuals with a high waist circumference, higher systolic and diastolic BP tended to be associated with worse cognition, while in individuals with a low waist circumference, higher systolic BP was associated with better cognition. The others physical, vascular and brain pathology markers did not modify the association between BP and cognition. Conclusions When examining various markers for physical, vascular and brain vulnerability, only waist circumference affected the association between BP and cognition. This warrants further research to evaluate whether waist circumference may be a marker in clinical practice influencing the use of antihypertensives in the oldest-old.

Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD).Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies.Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Introduction: Care for people with vascular cognitive impairment (VCI), like vascular dementia or post-stroke cognitive impairment, is provided by various healthcare professionals. People with VCI present in different settings like (acute) neurology, rehabilitation and dementia care, all with their own guidelines and workflow. We explored experiences and perspectives of healthcare professionals on care provision, organization and collaboration regarding care for people with VCI. Methods: We performed a qualitative focus group study in regions across the Netherlands. Focus groups were divided in three types: (i) primary care, (ii) secondary care and (iii) mixed focus groups with healthcare professionals from both settings. We included forty healthcare professionals across seven focus groups, including medical specialists, elderly care physicians, general practitioners, nurses, paramedics and case managers in dementia care. Inclusion ended when we reached thematic saturation, meaning new data did not provide additional (sub-)themes. Focus groups were audiotaped and transcribed verbatim. Transcripts were iteratively coded, recoded, analyzed and grouped into themes according to the inductive thematic analysis method by Braun & Clarke. Results: Three themes were identified. An overarching theme was “Knowledge and awareness of VCI.” Participants stated that the general public as well as healthcare professionals had insufficient knowledge of VCI. They agreed that awareness of the condition was a prerequisite for adequate care for people with VCI. The second theme was “Specific care.” Participants noted a lack of differentiation in current VCI care, while specific recommendations are needed for typical symptoms and fluctuations in functioning. Participants also highlighted the need to unburden informal caregivers, who struggle with symptoms like apathy or uncertainty of the disease course, described by one participant as a “no man's land”. The third theme was “Integrated care.” Current care for VCI was perceived as highly fragmented: various professionals provided a specific part, but a central lead or coordinator was often lacking. Participants proposed an integrated and transmural VCI-network. Discussion: More specific and integrated care is needed to accommodate people with VCI and informal caregivers, combining expertise from dementia and rehabilitation settings. Knowledge and awareness of VCI should be improved by providing (psycho-)education to professionals and the public.

The number of people living with dementia, such as Alzheimer's disease, is increasing worldwide. Persons with dementia often have a high risk of atherosclerotic cardiovascular disease and they are therefore theoretically eligible for treatment of hypertension and hyperlipidemia. However, in this population, beneficial and harmful effects of cardiovascular risk management (CVRM) may be different compared to older persons without cognitive impairment. Current CVRM guidelines are based on trials from which persons with dementia were excluded. In this narrative review, we will discuss how current guidelines can be translated to persons with dementia and which aspects should be taken into account when treating hypertension and hyperlipidemia to prevent major adverse cardiovascular events (MACE). Survival time is significantly shorter in persons with dementia. We therefore suggest that since the main goal of CVRM is prevention of MACE, first of all, the patient's life expectancy and treatment wishes should be evaluated. Risk assessment tools are to be used with care, as they tend to overestimate the 5- and 10-year risk of MACE and benefit from CVRM in the prevention of MACE in persons with dementia. When the clinician and patient have decided that treatment is initiated or intensified, patients should be closely monitored since they are at high risk for adverse drugs events and overtreatment due to the natural course of blood pressure in persons with dementia. In the event of intolerance or side effects, medication should be switched or withdrawn. For persons with dementia and limited life expectancy, deprescribing should be part of usual care.

Introduction: Research is lacking regarding the effect of cerebral small vessel disease (CSVD) on different domains of functioning and their interrelations. Network analyses provides a holistic overview of interrelationships between different variables. Therefore, we applied network analysis on data of older people with varying levels of CSVD and their cognitive, physical, emotional and daily functioning. Methods: We included participants (n=807) from the Amsterdam Aging Cohort. Inclusions criteria were a memory clinic visit including (i) comprehensive geriatric assessment, (ii) brain imaging and (iii) neuropsychological evaluation.CSVD was operationalized as White Matter Hyperintensities (WMH), according to the Fazekas scale, dividing the sample in three levels: no/mild WMH (Fazekas 0/1), moderate WMH (Fazekas 2) and severe WMH (Fazekas 3)Domains of functioning were operationalized as follows. Physical functioning: gait speed and handgrip strength (HGS). Cognitive functioning: composite z-scores in the domains memory, language, attention/speed and executive functioning. Daily functioning: Katz ADL and the Lawton iADL. Emotional functioning: Geriatric Depression Scale-15, Apathy (GDS-3A) and Depression (GDS-12D) subscales. Health related Quality of Life (hrQoL): EQ5D-VAS. We ran a network (mixed graphical model) to assess the associations between the domains of functioning. We tested whether these associations were different for different levels of CSVD in a moderated network model. Multiple regression, corrected for sex, age and education level, was used to assess the difference in domains of functioning between CSVD levels. Results: In the network model, more depressive and apathy symptoms are associated with lower hrQoL. Lower physical & cognitive functioning are associated with worse daily functioning (Figure). The moderated network did not significantly differ between CSVD levels. Yet, our multiple regression analyses did show differences that WMH severity is related with worse physical functioning, worse daily functioning, lower hrQoL, more apathy symptoms and lower cognitive functioning in the attention and language domains (Table). Discussion: Domains of functioning are highly connected in this older population, while CSVD is associated with worse functioning in all domains. This implicates that cognitive and emotional changes prevalent in CSVD (apathy, reduced speed) co-occur with worse daily functioning and decreased quality of life, warranting a holistic approach in clinical care.

Introduction: It is known that vascular damage is associated with decreased brain health. Therefore, the study VARIATION, focusing on vascular phenotypes in patients visiting a memory clinic, was launched as a substudy of the Amsterdam Ageing Cohort. The objective of this study is to assess micro and macrovascular function and damage in patients visiting the memory clinic and relate this to long term cognitive and functional outcomes. Here, we present preliminary baseline results of the first 51 participants. Methods: All patients underwent an extensive vascular assessment including blood pressure measurements (supine and standing), carotid pulse wave velocity, carotid stiffness index, intima media thickness, reactive hyperemia index (as a measure of microvascular function), estimated glomerular filtration rate, cerebral small vessel disease (WMH, lacunes, microbleeds) on 3T MRI, as well as cognitive and physical function measurements. Results: In this memory clinic population (N=51, mean (SD) age 80 (6), 31% women) 30% had subjective cognitive decline, 40% MCI, and 30% dementia. Both vascular dysfunction and damage was highly prevalent, with an impaired endothelial function of 35% (reactive hyperemia index 8.5 ms/). Mean (SD) systolic blood pressure was 138 ± 21 mmHg, and 33% had orthostatic hypotension. Furthermore, cerebral small vessel was highly prevalent on cerebral imaging, 55% of patients had Fazekas score >= 2, 20% had >= 3 microbleeds and lacunes were present in 18%. Discussion: In this preliminary results of VARIATION we presented an extensively vascular phenotyped memory-clinic cohort, with high prevalence of micro- and macrovascular damage. Data on if and how impaired vascular function is associated with cognitive and functional decline will follow.

Introduction: Arterial spin labeling (ASL) MRI, a non-invasive technique for imaging perfusion, now allows studying BBB permeability. The DEveloping BBB-ASL as a non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD) multi-cohort study integrates this modified BBB-ASL technique in several healthy and diseased populations (Table 1) to study methodological and clinical research questions (Table 2) on the ability of BBB-ASL as an early AD biomarker. Methods: DEBBIE-AD will enroll various cohorts with subjective cognitive decline, mild cognitive impairment, and AD dementia, as well as age-matched healthy controls, at seven sites (Table 1). Our newly developed BBB-ASL sequence — implemented with the vendor-independent MRI framework gammaSTAR — will be added to multiple MRI protocols. The BBB-ASL sequence combines time-encoded multi-post labeling delay pseudo-continuous ASL with a multi-echo 3D GRASE readout, allowing estimating CBF, ATT, and the BBB time of exchange (Tex). Data analyses will be conducted using ExploreASL. Beyond MRI standard sequences, including T1w, T2w, FLAIR, DWI, the DEBBIE clinical outcomes include amyloid-PET and blood and CSF fluid biomarkers (Table 1). Expected Results: Preliminary testing of the BBB-ASL has been conducted on 3T systems (different Siemens Heathineers scanners) in different cohorts at multiple sites. Data processing with ExploreASL includes FSL-FABBER4 for quantification, allowing harmonized image processing. An example of the mean and standard deviation Tex maps of two DEBBIE cohorts is shown in Figure 1 to illustrate the similarities of the Tex patterns from two cohorts of similar-aged healthy adults from different sites. Discussion: The DEBBIE-AD study aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies. The presented sequence may provide novel and unique insights into the staging of BBB permeability changes in groups at greater risk of developing AD, which may, in turn, provide new targets for treatment.

Objective: Cognitive impairment is highly prevalent among patients with heart failure (HF). International guidelines on the management of HF recommend screening for cognitive impairment and tailored care for patients with cognitive impairment. However, practical guidance is lacking. In this study, we explore cardiologists’ perspective on screening and care for cognitive impairment in patients with HF. Methods: We distributed an online survey to cardiologists from the Dutch working groups on Geriatric Cardiology and Heart Failure. It covered questions about current clinical practice, impact of cognitive impairment on clinical decision-making, and their knowledge and skills to recognize cognitive impairment. Results: Thirty-six out of 55 invited cardiologists responded. Only 3% of the cardiologists performed structured cognitive screening intheir clinical practice, while 83% stated that not enough attention has been paid to cognitive impairment. More than 60% of the cardiologists wanted more training in recognizing cognitive impairment and three-quarters said that knowing about cognitive impairment would change their treatment plan. Eighty percent agreed that systematic cognitive screening would benefit cardiac patients and 74% wished to implement a Heart-Brain clinic. Time and expertise were addressed as the major barriers to screening for cognitive impairment (Figure). Discussion: Although cardiologists are aware of the impact of cognitive impairment and prefer structured screening, this is still unavailable in most cardiology outpatient clinics due to lack of time and expertise. The Heart-Brain care path could facilitate this screening.

Introduction: Globally, women with dementia have a higher disease burden than men with dementia. In addition, women with diabetes especially are at higher risk for cognitive impairment and dementia compared to men with diabetes. Differences in the influence of diabetes on the cerebral vasculature and brain structure may contribute to these sex-specific differences. We examined sex-specific patterns in the relationship between diabetes and brain structure, as well as diabetes and cognitive function. We aimed to investigate if women with diabetes have a higher incidence of cerebral vascular impairment compared to men, and whether this also translates in differences in cognitive function between men and women. Methods: In total, 893 patients [age 79 ± 6.6 years, 446 (50%) women] from the Amsterdam Ageing Cohort with available data on brain structure (assessed by an MRI or CT scan) and cognitive function and were included. All patients underwent a thorough standardized clinical and neuropsychological assessment (including tests on memory, executive functioning, processing speed, language). Brain structure abnormalities were quantified using visual scales, including lacunes, white matter hyperintensities, atrophy and microbleeds. Results: Cross-sectional multivariable regression analyses showed that diabetes was associated with increased incidence of cerebral lacunes and brain atrophy in women (OR 2.18 (1.00–4.72) but not in men. Furthermore, diabetes was associated with decreased executive function, processing speed and language in women [B −0.07 (0.00–0.13), −0.06 (0.02–0.10) and −0.07 (0.01–0.12) resp.] but not in men. These effects persisted when correcting for lifestyle factors, other cardiovascular diseases and cardiovascular risk factors, age and level of education. Discussion: in our cohort of elderly patients, diabetes is related to increased risk of having lacunes, brain atrophy and impaired cognitive function in women but not in men. Furthermore, diabetes is a significant risk factor for functional cognitive impairment in women, but not in men. Further research is required to understand the mechanisms behind this inequality, in terms of biological (sex) differences, as well as social (gender) differences, in order to achieve personalised care and improve preventive clinical practice for all patients.

Introduction: The prevalence of atherosclerotic cardiovascular diseases and its associated mortality are increasing worldwide. In persons with cognitive impairment, the potential benefits from treatment of hypertension and dyslipidaemia may be overestimated due to competing mortality risks related to cognitive impairment. We therefore aim to explore the association between cardiovascular risk and all-cause mortality in a memory clinic population, and whether this relation is modified by cognitive and physical performance. Methods: All patients from the Amsterdam Ageing Cohort who visited the memory clinic were included. Cardiovascular risk was assessed with the SCORE2-OP, a validated instrument to estimate 5- and 10-year risk for non-fatal myocardial infarction, non-fatal stroke and cardiovascular mortality in persons aged ≥70 years. A 10-year risk of

Summary: Background: FindMyApps is a tablet-based eHealth intervention designed to help people learn to use a tablet and find easy-to-use apps. This study evaluated the effectiveness of FindMyApps for supporting social health of people living with dementia, and sense of competence of their informal caregivers. Methods: A single-centre, two-arm, non-blinded randomised controlled trial was conducted (Netherlands Trial Register NL8157). From 1st January 2020 to 31st July 2022, community-dwelling people in the Netherlands with a pre-established diagnosis of mild cognitive impairment (MCI) or dementia (Brief Cognitive Rating Scale 17–32), an informal caregiver and internet connection were allocated by block randomisation to receive FindMyApps or digital care-as-usual. Primary outcomes (measured at baseline and after three months) for people with dementia/MCI were self-management (Adult Social Care Outcomes Toolkit total score) and social participation (Maastricht Social Participation Profile frequency and diversity scores), and for caregivers, sense of competence (Short Sense of Competence Questionnaire total score). Between-group differences were tested by MANCOVA or ANCOVA (alpha = 0.05). Findings: 150 dyads were randomised (FindMyApps n = 76, care-as-usual n = 74). Follow-up data were available for 128 dyads (FindMyApps n = 64, care-as-usual n = 64), who were included in the analysis in the trial arm to which they were assigned. No harms of the intervention were identified. There were no statistically significant differences in outcomes for people with dementia/MCI at group level. Diagnosis and experiencing apathy appeared to be relevant effect modifiers of secondary outcomes (neuropsychiatric symptoms, positive affect, sense of belonging, and pleasurable activities). Caregivers who received FindMyApps had higher sense of competence at three months (F [1,123] = 7.01, p = 0.0092, η2 = 0.054). Interpretation: Overall we found no evidence that the FindMyApps intervention better supported social participation or self-management of people with MCI/dementia than digital care-as-usual. FindMyApps does seem to better support informal caregivers’ sense of competence. For people with a diagnosis of mild dementia and older people, better tailored interventions, implementation and outcome measures may be needed. Funding: Marie Skłodowska Curie Actions Innovative Training Network H2020 MSCA ITN, grant agreement number 813196.

IntroductionFindMyApps is a tablet-based eHealth intervention, designed to improve social health in people with mild dementia or mild cognitive impairment.MethodsFindMyApps has been subject to a randomized controlled trial (RCT), Netherlands Trial Register NL8157. Following UK Medical Research Council guidance, a mixed methods process evaluation was conducted. The goal was to investigate the quantity and quality of tablet use during the RCT, and which context, implementation, and mechanisms of impact (usability, learnability and adoption) factors might have influenced this. For the RCT, 150 community dwelling people with dementia and their caregivers were recruited in the Netherlands. For the process evaluation, tablet-use data were collected by proxy-report instrument from all participants' caregivers, FindMyApps app-use data were registered using analytics software among all experimental arm participants, and semi-structured interviews (SSIs) were conducted with a purposively selected sample of participant-caregiver dyads. Quantitative data were summarized and between group differences were analyzed, and qualitative data underwent thematic analysis.ResultsThere was a trend for experimental arm participants to download more apps, but there were no statistically significant differences between experimental and control arm participants regarding quantity of tablet use. Qualitative data revealed that experimental arm participants experienced the intervention as easier to use and learn, and more useful and fun than control arm participants. Adoption of tablet app use was lower than anticipated in both arms.ConclusionsA number of context, implementation and mechanism of impact factors were identified, which might explain these results and may inform interpretation of the pending RCT main effect results. FindMyApps seems to have had more impact on the quality than quantity of home tablet use.

Samenvatting Achtergrond: Computertools zoals digitale (web-based) cognitieve testen, diagnostische tools en automatisch gegenereerde hulpmiddelen voor het arts-patiëntgesprek voor de geheugenpolikliniek zijn in opkomst. Deze tools kunnen worden ingezet om clinici te ondersteunen bij de diagnostische besluitvorming en het communiceren van de diagnose en prognose. In dit onderzoek brengen we door middel van een vragenlijst de meningen van clinici, patiënten en naasten, de zogenoemde ‘eindgebruikers’, voor het gebruik van computertools in geheugenpoliklinieken in kaart. Daarnaast identificeren we belemmerende en faciliterende factoren voor de daadwerkelijke toepassing. Methode: Tussen juli en oktober 2020 nodigden we Europese clinici (n=109, leeftijd 45±10j; 47% vrouw) uit om deel te nemen aan een online vragenlijst. Een tweede vragenlijst werd verstuurd naar patiënten (n=50, leeftijd 73±8j, 34% vrouw) met subjectieve cognitieve klachten (SCD, n= 21), milde cognitieve achteruitgang (MCI, n=16) en dementie (n=13) en naasten (n=46, 65±12j, 54% vrouw). Resultaten: Driekwart van alle deelnemers was positief over het gebruik van computertools in geheugenpoliklinieken. Faciliterende factoren waren onder andere gebruiksvriendelijkheid en hogere diagnostische nauwkeurigheid. Onder barrières vielen (twijfels aan) betrouwbaarheid en validiteit en verlies van klinische autonomie. De deelnemers vinden dat tools moeten worden gebruikt ter aanvulling op de huidige werkwijze en niet als vervanging. Discussie: Onze resultaten vormen een belangrijke stap in het iteratieve ontwikkelproces van computertools voor geheugenpoliklinieken, dat samen met eindgebruikers doorlopen wordt. Abstract Introduction: Computer tools based on artificial intelligence could aid clinicians in memory clinics by supporting diagnostic decision-making and communicating diagnosis and prognosis. We aimed to identify preferences of end-users, and barriers and facilitators for using computer tools in memory clinics. Methods: Between July and October 2020, we invited European clinicians (n=109, age 45±10y; 47% female) to participate in an online questionnaire. A second questionnaire was sent to patients (n=50, age 73±8y, 34% female) with subjective cognitive complaints (SCD, n=21), mild cognitive impairment (MCI, n=16) and dementia (n=13) and care partners (n=46, 65±12y, 54% female). Results: The vast majority (75%) of all participants positively valued the use of computer tools in memory clinics. Facilitating factors included user-friendliness and increased diagnostic accuracy. Barriers included (doubts relating) reliability and validity of the tool and loss of clinical autonomy. The participants believe that tools should be used in addition to the current working method and not as a replacement. Discussion: Our results provide an important step in the iterative process of developing computer tools for memory clinics in co-creation with end-users and could guide successful implementation.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has necessitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identified as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescribing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post–COVID-19 patients, hospitalized during the first wave of COVID-19 in the Netherlands, 3 months after discharge. Methods This prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3 months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs. Results Ninety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identified PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identified ICU admission (OR 6.08, 95% CI 2.16–17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34–21.5) as independent risk factors for PEs. Conclusions PEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID-19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.

Abstract Aims This study aims to assess the presence of geriatric domain impairments in an older heart failure (HF) outpatient population and to relate these domain impairments with 1 year mortality risk in comparison with a geriatric outpatient population without HF. Methods and results Data were used from two different prospective cohort studies: 241 outpatients with HF (mean age 78 ± 9 years, 48% female) and 686 geriatric outpatients (mean age 80 ± 7 years, 55% female). We similarly assessed the following geriatric domains in both cohorts: physical function, nutritional status, polypharmacy, cognitive function, and activities in daily living. Cox proportional hazards analyses were used to relate individual domains to 1 year mortality risk in both populations and to compare 1 year mortality risk between both populations. Of the patients with HF, 34% had impairments in ≥3 domains, compared with 38% in geriatric patients. One‐year mortality rates were 13% and 8%, respectively, in the HF and geriatric populations; age‐adjusted and sex‐adjusted hazard ratio (95% confidence interval) for patients with HF compared with geriatric patients was 1.7 (1.3–2.6). The individual geriatric domains were similarly associated with 1 year mortality risk in both populations. Compared with zero to two impaired domains, age‐adjusted and sex‐adjusted mortality risk (hazard ratio, 95% confidence interval) for three, four, or five impaired domains ranged from 1.6 (0.6–4.2) to 6.5 (2.1–20.1) in the HF population and from 1.4 (0.7–2.9) to 7.9 (2.9–21.3) in the geriatric population. Conclusions In parallel with geriatric patients, patients with HF often have multiple geriatric domain impairments that adversely affect their prognosis. This similarity together with the findings that patients with HF have a higher 1 year mortality risk than a general geriatric population supports the integration of a multi‐domain geriatric assessment in outpatient HF care.

Abstract Background For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps intervention has been developed with and for people with dementia and their caregivers, to help them use tablets to facilitate self-management and engagement in meaningful social activities. A feasibility study and exploratory pilot trial evaluating FindMyApps have been carried out. This definitive trial further evaluates the effectiveness of the intervention and, for the first time, the cost-effectiveness. Methods A randomized controlled non-blinded single-center two-arm superiority trial will be conducted. Community-dwelling people with Mild Cognitive Impairment (MCI), or dementia with a Mini Mental-State Examination (MMSE) of > 17 and

IntroductionGlobally, women with dementia have a higher disease burden than men with dementia. In addition, women with diabetes especially are at higher risk for cognitive impairment and dementia compared to men with diabetes. Differences in the influence of diabetes on the cerebral vasculature and brain structure may contribute to these sex-specific differences. We examined sex-specific patterns in the relationship between diabetes and brain structure, as well as diabetes and cognitive function.MethodsIn total, 893 patients [age 79 ± 6.6 years, 446 (50%) women] from the Amsterdam Ageing Cohort with available data on brain structures (assessed by an MRI or CT scan) and cognitive function were included. All patients underwent a thorough standardized clinical and neuropsychological assessment (including tests on memory, executive functioning, processing speed, language). Brain structure abnormalities were quantified using visual scales.ResultsCross-sectional multivariable regression analyses showed that diabetes was associated with increased incidence of cerebral lacunes and brain atrophy in women (OR 2.18 (1.00–4.72) but not in men. Furthermore, diabetes was associated with decreased executive function, processing speed and language in women [B −0.07 (0.00–0.13), −0.06 (0.02–0.10) and −0.07 (0.01–0.12) resp.] but not in men.ConclusionsDiabetes is related to increased risk of having lacunes, brain atrophy and impaired cognitive function in women but not in men. Further research is required to understand the time trajectory leading up to these changes and to understand the mechanisms behind them in order to improve preventive health care for both sexes.

Abstract Aims Physical frailty screening is more commonly performed at outpatient heart failure (HF) clinics. However, this does not incorporate other common geriatric domains. This study assesses whether a multidomain geriatric assessment, in comparison with HF severity or physical frailty, is associated with short‐term adverse outcomes. Methods and results This is a prospective cohort study of 197 patients with HF (mean age 78, 44% female) attending outpatient HF clinics. HF severity was assessed with New York Heart Association class (I‐II versus III‐IV) and N‐terminal pro b‐type natriuretic peptide levels. Physical frailty was assessed with the Fried frailty criteria (not frail, pre‐frail, and frail). The following geriatric domains were assessed: physical function, nutrition, polypharmacy, cognition, and dependency in activities of daily living. Logistic regression analyses adjusted for age, sex, diabetes and kidney function assessed 3 month risk of adverse health outcomes (emergency department visits, hospital admissions, and/or death) according to HF severity, physical frailty, and number of affected domains. Number (%) of patients with HF with no, 1, 2, and ≥3 domains affected were 36 (18%), 61 (31%), 58 (29%), and 42 (21%). Seventy‐four adverse outcomes were experienced in 50 patients at follow‐up. Severity of HF and physical frailty were not significantly associated with an increased risk of adverse health outcomes. However, increasing number of affected domains were significantly associated with an increased risk of adverse outcomes. Compared with no domains affected, odds ratios (95% confidence interval) for 1, 2, and ≥3 domains were 1.8 (0.5–6.5), 4.5 (1.3–15.4), and 7.2 (2.0–26.3) (P‐trend

IntroductionSeveral studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Materials and MethodsWe included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE.ResultsThe machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis, and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status.ConclusionsGut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.

BackgroundComputer tools based on artificial intelligence could aid clinicians in memory clinics in several ways, such as by supporting diagnostic decision-making, web-based cognitive testing, and the communication of diagnosis and prognosis. ObjectiveThis study aims to identify the preferences as well as the main barriers and facilitators related to using computer tools in memory clinics for all end users, that is, clinicians, patients, and care partners. MethodsBetween July and October 2020, we sent out invitations to a web-based survey to clinicians using the European Alzheimer’s Disease Centers network and the Dutch Memory Clinic network, and 109 clinicians participated (mean age 45 years, SD 10; 53/109, 48.6% female). A second survey was created for patients and care partners. They were invited via Alzheimer Europe, Alzheimer’s Society United Kingdom, Amsterdam Dementia Cohort, and Amsterdam Aging Cohort. A total of 50 patients with subjective cognitive decline, mild cognitive impairment, or dementia (mean age 73 years, SD 8; 17/34, 34% female) and 46 care partners (mean age 65 years, SD 12; 25/54, 54% female) participated in this survey. ResultsMost clinicians reported a willingness to use diagnostic (88/109, 80.7%) and prognostic (83/109, 76.1%) computer tools. User-friendliness (71/109, 65.1%); Likert scale mean 4.5, SD 0.7), and increasing diagnostic accuracy (76/109, 69.7%; mean 4.3, SD 0.7) were reported as the main factors stimulating the adoption of a tool. Tools should also save time and provide clear information on reliability and validity. Inadequate integration with electronic patient records (46/109, 42.2%; mean 3.8, SD 1.0) and fear of losing important clinical information (48/109, 44%; mean 3.7, SD 1.2) were most frequently indicated as barriers. Patients and care partners were equally positive about the use of computer tools by clinicians, both for diagnosis (69/96, 72%) and prognosis (73/96, 76%). In addition, most of them thought favorably regarding the possibility of using the tools themselves. ConclusionsThis study showed that computer tools in memory clinics are positively valued by most end users. For further development and implementation, it is essential to overcome the technical and practical barriers of a tool while paying utmost attention to its reliability and validity.

Abstract Background There is increasing evidence that dementia risk associated with vascular disorders is age dependent. Large population-based studies of incident dementia are necessary to further elucidate this effect. Therefore, the aim of the present study was to determine the association of vascular disorders with incident dementia in different age groups in a large primary care database. Methods We included 442,428 individuals without dementia aged ≥ 65 years from the longitudinal primary care Integrated Primary Care Information (IPCI) database. We determined in 6 age groups (from 65–70 to ≥ 90 years) the risk of hypertension, diabetes mellitus, dyslipidemia, stroke, myocardial infarction, heart failure, and atrial fibrillation for all-cause dementia using incidence rate ratios, Cox regression, and Fine and Gray regression models. Results The mean age at inclusion of the total study sample was 72.4 years, 45.7% of the participants were male, and median follow-up was 3.6 years. During 1.4 million person-years of follow-up, 13,511 individuals were diagnosed with dementia. The risk for dementia decreased with increasing age for all risk factors and was no longer significant in individuals aged ≥ 90 years. Adjusting for mortality as a competing risk did not change the results. Conclusions We conclude that vascular disorders are no longer a risk factor for dementia at high age. Possible explanations include selective survival of individuals who are less susceptible to the negative consequences of vascular disorders and differences in follow-up time between individuals with and without a vascular disorder. Future research should focus on the identification of other risk factors than vascular disorders, for example, genetic or inflammatory processes, that can potentially explain the strong age-related increase in dementia risk.

Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer’s disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.

Abstract Introduction Weight loss is associated with higher mortality and progression of cognitive decline, but its associations with magnetic resonance imaging (MRI) changes related to Alzheimer's disease (AD) are unknown. Methods We included 412 patients from the NUDAD project, comprising 129 with AD dementia, 107 with mild cognitive impairment (MCI), and 176 controls. Associations between nutritional status and MRI measures were analyzed using linear regression, adjusted for age, sex, education, cognitive functioning, and cardiovascular risk factors. Results Lower body mass index (BMI), fat mass (FM), and fat free mass index were associated with higher medial temporal atrophy (MTA) scores. Lower BMI, FM, and waist circumference were associated with more microbleeds. Stratification by diagnosis showed that the observed associations with microbleeds were only significant in MCI. Discussion Lower indicators of nutritional status were associated with more MTA and microbleeds, with largest effect sizes in MCI.

Abstract Background The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study. Methods The EMIF-AD 90+ Study aimed to enroll 80 cognitively normal subjects and 40 subjects with cognitive impairment aged 90 years or older. Cognitive impairment was operationalized as amnestic mild cognitive impairment (aMCI), or possible or probable Alzheimer’s Disease (AD). The study was part of the European Medical Information Framework for AD (EMIF-AD) and was conducted at the Amsterdam University Medical Centers (UMC) and at the University of Manchester. We will test whether cognitive resilience is associated with cognitive reserve, vascular comorbidities, mood, sleep, sensory system capacity, physical performance and capacity, genetic risk factors, hallmarks of ageing, and markers of neurodegeneration. Markers of neurodegeneration included an amyloid positron emission tomography, amyloid β and tau in cerebrospinal fluid/blood and neurophysiological measures. Discussion The EMIF-AD 90+ Study will extend our knowledge on resilience to cognitive impairment in the oldest-old by extensive phenotyping of the subjects and the measurement of a wide range of potential protective factors, hallmarks of aging and markers of neurodegeneration. Trial registration Nederlands Trial Register NTR5867. Registered 20 May 2016.

An amendment to this paper has been published and can be accessed via the original article.

BACKGROUND:Frail elderly people experience elevated mortality. However, no consensus exists on the definition of frailty, and many frailty scores have been developed. The main aim of this study was to compare the association between 35 frailty scores and incident cardiovascular disease (CVD), incident cancer, and all-cause mortality. Also, we aimed to assess whether frailty scores added predictive value to basic and adjusted models for these outcomes. METHODS AND FINDINGS:Through a structured literature search, we identified 35 frailty scores that could be calculated at wave 2 of the English Longitudinal Study of Ageing (ELSA), an observational cohort study. We analysed data from 5,294 participants, 44.9% men, aged 60 years and over. We studied the association between each of the scores and the incidence of CVD, cancer, and all-cause mortality during a 7-year follow-up using Cox proportional hazard models at progressive levels of adjustment. We also examined the added predictive performance of each score on top of basic models using Harrell's C statistic. Using age of the participant as a timescale, in sex-adjusted models, hazard ratios (HRs) (95% confidence intervals) for all-cause mortality ranged from 2.4 (95% CI: 1.7-3.3) to 26.2 (95% CI: 15.4-44.5). In further adjusted models including smoking status and alcohol consumption, HR ranged from 2.3 (95% CI: 1.6-3.1) to 20.2 (95% CI: 11.8-34.5). In fully adjusted models including lifestyle and comorbidity, HR ranged from 0.9 (95% CI: 0.5-1.7) to 8.4 (95% CI: 4.9-14.4). HRs for CVD and cancer incidence in sex-adjusted models ranged from 1.2 (95% CI: 0.5-3.2) to 16.5 (95% CI: 7.8-35.0) and from 0.7 (95% CI: 0.4-1.2) to 2.4 (95% CI: 1.0-5.7), respectively. In sex- and age-adjusted models, all frailty scores showed significant added predictive performance for all-cause mortality, increasing the C statistic by up to 3%. None of the scores significantly improved basic prediction models for CVD or cancer. A source of bias could be the differences in mortality follow-up time compared to CVD/cancer, because the existence of informative censoring cannot be excluded. CONCLUSION:There is high variability in the strength of the association between frailty scores and 7-year all-cause mortality, incident CVD, and cancer. With regard to all-cause mortality, some scores give a modest improvement to the predictive ability. Our results show that certain scores clearly outperform others with regard to three important health outcomes in later life. Finally, we think that despite their limitations, the use of frailty scores to identify the elderly population at risk is still a useful measure, and the choice of a frailty score should balance feasibility with performance.

BackgroundWe investigated whether cardiac parameters in young adulthood are associated with indicators of brain health in midlife. Methods and ResultsThis study includes 648 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study (52% women, 38% black). We studied associations of cardiac parameters assessed by echocardiography (left ventricular ejection fraction, left atrial volume, and left ventricular mass) in young adulthood (mean age: 30 years) with brain measures obtained by magnetic resonance imaging (total brain, gray and white matter volume, white matter integrity, abnormal white matter) in midlife (mean age: 50 years). In 406 individuals with complete measurements, higher left atrial volume was associated with lower white matter fractional anisotropy, independent of traditional cardiovascular risk factors (β=−0.002; P

Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) and to investigate their clinical value in a large memory clinic cohort.Methods: We included 2,934 patients (age 67 ± 9 years; 1,391 [47%] female; MMSE 24 ± 5) from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline). We analyzed the effect of age, APOE e4 and diagnosis on visual ratings using linear regression analyses. Subsequently, we compared diagnostic and predictive value in three age-groups (75 years).Results: Linear regression analyses showed main effects of age and diagnosis and an interaction age*diagnosis for MTA, PA, and GCA. For MTA the interaction effect indicated steeper age effects in MCI and AD than in controls. PA and GCA increased with age in MCI and controls, while AD patients have a high score, regardless of age. For WMH we found a main effect of age, but not of diagnosis. For MTA, GCA and PA, diagnostic value was best in patients 75 years.Conclusion: Visual ratings of atrophy and WMH were differently affected by age and diagnosis, requiring an age-specific approach in clinical practice. Their diagnostic value seems strongest in younger patients.

ObjectivesAssessment of the association of blood pressure measurements in supine and standing position after a postural change, as a proxy for blood pressure regulation, with standing balance in a clinically relevant cohort of elderly, is of special interest as blood pressure may be important to identify patients at risk of having impaired standing balance in routine geriatric assessment.Materials and methodsIn a cross-sectional cohort study, 197 community-dwelling elderly referred to a geriatric outpatient clinic of a middle-sized teaching hospital were included. Blood pressure was measured intermittently (n = 197) and continuously (subsample, n = 58) before and after a controlled postural change from supine to standing position. The ability to maintain standing balance was assessed during ten seconds of side-by-side, semi-tandem and tandem stance, with both eyes open and eyes closed. Self-reported impaired standing balance and history of falls were recorded by questionnaires. Logistic regression analyses were used to examine the association between blood pressure and 1) the ability to maintain standing balance; 2) self-reported impaired standing balance; and 3) history of falls, adjusted for age and sex.ResultsBlood pressure decrease after postural change, measured continuously, was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed and with increased self-reported impaired standing balance and falls. Presence of orthostatic hypotension was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed for both intermittent and continuous measurements and with increased self-reported impaired standing balance for continuous measurements.ConclusionContinuous blood pressure measurements are of additional value to identify patients at risk of having impaired standing balance and may therefore be useful in routine geriatric care.