Computerized decision support is an effective approach to select memory clinic patients for amyloid-PET.

BACKGROUND: The use of amyloid-PET in dementia workup is upcoming. At the same time, amyloid-PET is costly and limitedly available. While the appropriate use criteria (AUC) aim for optimal use of amyloid-PET, their limited sensitivity hinders the translation to clinical practice. Therefore, there is a need for tools that guide selection of patients for whom amyloid-PET has the most clinical utility. We aimed to develop a computerized decision support approach to select patients for amyloid-PET. METHODS: We included 286 subjects (135 controls, 108 Alzheimer's disease dementia, 33 frontotemporal lobe dementia, and 10 vascular dementia) from the Amsterdam Dementia Cohort, with available neuropsychology, APOE, MRI and [18F]florbetaben amyloid-PET. In our computerized decision support approach, using supervised machine learning based on the DSI classifier, we first classified the subjects using only neuropsychology, APOE, and quantified MRI. Then, for subjects with uncertain classification (probability of correct class (PCC) < 0.75) we enriched classification by adding (hypothetical) amyloid positive (AD-like) and negative (normal) PET visual read results and assessed whether the diagnosis became more certain in at least one scenario (PPC≥0.75). If this was the case, the actual visual read result was used in the final classification. We compared the proportion of PET scans and patients diagnosed with sufficient certainty in the computerized approach with three scenarios: 1) without amyloid-PET, 2) amyloid-PET according to the AUC, and 3) amyloid-PET for all patients. RESULTS: The computerized approach advised PET in n = 60(21%) patients, leading to a diagnosis with sufficient certainty in n = 188(66%) patients. This approach was more efficient than the other three scenarios: 1) without amyloid-PET, diagnostic classification was obtained in n = 155(54%), 2) applying the AUC resulted in amyloid-PET in n = 113(40%) and diagnostic classification in n = 156(55%), and 3) performing amyloid-PET in all resulted in diagnostic classification in n = 154(54%). CONCLUSION: Our computerized data-driven approach selected 21% of memory clinic patients for amyloid-PET, without compromising diagnostic performance. Our work contributes to a cost-effective implementation and could support clinicians in making a balanced decision in ordering additional amyloid PET during the dementia workup.

Regional MRI volumetry using NeuroQuant versus visual rating scales in patients with cognitive impairment and dementia.

BACKGROUND AND PURPOSE: The aims were to compare the novel regional brain volumetric measures derived by the automatic software NeuroQuant (NQ) with clinically used visual rating scales of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal (GCA-f), and posterior atrophy (PA) brain regions, assessing their diagnostic validity, and to explore if combining automatic and visual methods would increase diagnostic prediction accuracy. METHODS: Brain magnetic resonance imaging (MRI) examinations from 86 patients with subjective and mild cognitive impairment (i.e., non-dementia, n = 41) and dementia (n = 45) from the Memory Clinic at Oslo University Hospital were assessed using NQ volumetry and with visual rating scales. Correlations, receiver operating characteristic analyses calculating area under the curves (AUCs) for diagnostic accuracy, and logistic regression analyses were performed. RESULTS: The correlations between NQ volumetrics and visual ratings of corresponding regions were generally high between NQ hippocampi/temporal volumes and MTA (r = -0.72/-0.65) and between NQ frontal volume and GCA-f (r = -0.62) but lower between NQ parietal/occipital volumes and PA (r = -0.49/-0.37). AUCs of each region, separating non-dementia from dementia, were generally comparable between the two methods, except that NQ hippocampi volume did substantially better than visual MTA (AUC = 0.80 vs. 0.69). Combining both MRI methods increased only the explained variance of the diagnostic prediction substantially regarding the posterior brain region. CONCLUSIONS: The findings of this study encourage the use of regional automatic volumetry in locations lacking neuroradiologists with experience in the rating of atrophy typical of neurodegenerative diseases, and in primary care settings.

Use of a digital tool to support the diagnostic process in memory clinics-a usability study.

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.

cCOG Web-Based Cognitive Assessment Tool.

Cognitive testing is an essential part of clinical diagnostics and clinical trials in Alzheimer's disease. Digital cognitive tests hold a great opportunity to provide more versatile and cost-efficient patient pathways through flexible testing including at home. In this work, we describe a web-based cognitive test, cCOG, that can be used in screening, differential diagnosis, and monitoring the progression of neurodegenerative diseases.

Is it time for Heart-Brain clinics? A clinical survey and proposition to improve current care for cognitive problems in heart failure.

BACKGROUND: 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. We give an example of a multidisciplinary Heart-Brain care pathway that facilitates screening 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% performed structured cognitive screening, while 83% stated that not enough attention is paid to cognitive impairment. More than half of the cardiologists desired more training in recognizing cognitive impairment and three-quarters indicated that knowing about cognitive impairment would change their treatment plan. Eighty percent agreed that systematic cognitive screening would benefit their patients and 74% wished to implement a Heart-Brain clinic. Time and expertise were addressed as the major barriers to screening for cognitive impairment. CONCLUSION: Although cardiologists are aware of the clinical relevance of screening for cognitive impairment in cardiology patients, such clinical conduct is not yet commonly practiced due to lack of time and expertise. The Heart-Brain care pathway could facilitate this screening, thus improving personalized care in cardiology.

Embedding routine health care data in clinical trials: with great power comes great responsibility.

Randomised clinical trials (RCTs) are vital for medical progress. Unfortunately, 'traditional' RCTs are expensive and inherently slow. Moreover, their generalisability has been questioned. There is considerable overlap in routine health care data (RHCD) and trial-specific data. Therefore, integration of RHCD in an RCT has great potential, as it would reduce the effort and costs required to collect data, thereby overcoming some of the major downsides of a traditional RCT. However, use of RHCD comes with other challenges, such as privacy issues, as well as technical and practical barriers. Here, we give a current overview of related initiatives on national cardiovascular registries (Netherlands Heart Registration, Heart4Data), showcasing the interrelationships between and the relevance of the different registries for the practicing physician. We then discuss the benefits and limitations of RHCD use in the setting of a pragmatic RCT from a cardiovascular perspective, illustrated by a case study in heart failure.

Vascular cognitive impairment: When memory loss is not the biggest challenge.

OBJECTIVES: Vascular cognitive impairment is the second most common type of cognitive impairment. Care needs of community-dwelling people with vascular cognitive impairment and their caregivers have not been thoroughly studied. Therefore, we aimed to explore care needs of people with vascular cognitive impairment and their family caregivers. DESIGN: A qualitative interview study. SETTING AND PARTICIPANTS: Participants were purposefully sampled community-dwelling people with vascular cognitive impairment and their family caregivers. METHODS: Interviews were audiotaped and transcribed verbatim. Analysis and data collection followed an iterative process, until data saturation was achieved. We conducted 18 interviews (nine people with vascular cognitive impairment and nine caregivers), concerning 13 unique people with vascular cognitive impairment. We analyzed the data using inductive thematic analysis following the Braun & Clark method. The study was reported in accordance with the COREQ criteria. FINDINGS: Five themes were identified in the care needs reported by people with vascular cognitive impairment and family caregivers: (1) Specific information need with subtheme (1A) No memory problem, no dementia? (2) Being respected as a person, (3) Differing concerns about the future, (4) The roles of the caregiver and (5) Decisiveness from professional healthcare. CONCLUSIONS AND IMPLICATIONS: The care needs of people with vascular cognitive impairment and their caregivers were affected by (a lack of knowledge about) the characteristic symptoms of this condition. Participants equated cognitive impairment or dementia to memory loss ("Alzheimerization"), although memory loss was not their biggest challenge. People with vascular cognitive impairment and caregivers preferred resolute and decisive healthcare professionals. These professionals activate the person with vascular cognitive impairment who lacks initiative and diminishe role conflict of the caregiver. Care for people with vascular cognitive impairment and their caregivers could be improved by providing tailored information, promoting awareness of neuropsychiatric symptoms, particularly apathy, and by healthcare professionals providing more guidance in decision-making.

Minding menopause in patients with cognitive impairment: a patient's perspective and reflections on clinical practice.

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.

Young-onset dementia in memory clinics in the Netherlands: Study design and description of PRECODE-GP.

The disease trajectory and healthcare requirements of patients with young-onset dementia (YOD) differ from those of older patients. Accurate data about YOD is crucial to improve diagnosis and optimize care. PRECODE-GP aims to set up a prospective national database of patients with YOD to gain insight into the occurrence and characteristics of patients with YOD in memory clinics in the Netherlands. The national database includes data from dementia patients aged <70 years at diagnosis, collected by local memory clinics (MCs). Data included demographic information, clinical variables, and (etiological) diagnoses. Between July 2019 and December 2022, 781 patients with a mean age of 62±6y at diagnosis (range 37 to 69y) were included from 39 MCs. Most (n = 547,70%) were diagnosed with dementia due to Alzheimer's disease (AD). Patients with Frontotemporal lobe dementia (FTD, n = 87, 11%) were youngest (61±6.0y). Over half (55%) of patients were experiencing symptoms for ≥2 years. We initiated a Dutch national YOD database to improve diagnosis and care for this underrepresented and vulnerable patient group. The database provides a basis for future in-depth studies on YOD.

Orthostatic hypotension and its association with cerebral small vessel disease in a memory clinic population.

BACKGROUND: Orthostatic hypotension (OH), an impaired blood pressure (BP) response to postural change, has been associated with cognitive decline and dementia, possibly through cerebral small vessel disease (CSVD). We hypothesized that longer duration of BP drop and a larger BP drop is associated with increased risk of CSVD. METHODS: This cross-sectional study included 3971 memory clinic patients (mean age 68 years, 45% female, 42% subjective cognitive complaints, 17% mild cognitive impairment, 41% dementia) from the Amsterdam Ageing Cohort and Amsterdam Dementia Cohort. Early OH (EOH) was defined as a drop in BP of ±20 mmHg systolic and/or 10 mmHg diastolic only at 1 min after standing, and delayed/prolonged OH (DPOH) at 1 and/or 3 min after standing. Presence of CSVD [white matter hyperintensities (WMH), lacunes, microbleeds] was assessed with MRI ( n  = 3584) or CT brain (n = 389). RESULTS: The prevalence of early OH was 9% and of delayed/prolonged OH 18%. Age- and sex-adjusted logistic regression analyses showed that delayed/prolonged OH, but not early OH, was significantly associated with a higher burden of WMH (OR, 95%CI: 1.21, 1.00-1.46) and lacunes (OR, 95%CI 1.34, 1.06-1.69), but not microbleeds (OR, 95%CI 1.22, 0.89-1.67). When adjusting for supine SBP, these associations attenuated (ORs, 95%CI for WMH 1.04, 0.85-1.27; for lacunes 1.21, 0.91-1.62; for microbleeds 0.95, 0.68-1.31). A larger drop in SBP was associated with increased risk of WMH and microbleeds, however, when adjusted for supine SBP, this effect diminished. CONCLUSIONS: Among memory clinic patients, DPOH is more common than EOH. While longer duration and larger magnitude of BP drop coincided with a higher burden of CSVD, these associations were largely explained by high supine BP.

Communication about diagnosis, prognosis, and prevention in the memory clinic: perspectives of European memory clinic professionals.

BACKGROUND: The paradigm shift towards earlier Alzheimer's disease (AD) stages and personalized medicine creates new challenges for clinician-patient communication. We conducted a survey among European memory clinic professionals to identify opinions on communication about (etiological) diagnosis, prognosis, and prevention, and inventory needs for augmenting communication skills. METHODS: Memory clinic professionals (N = 160) from 21 European countries completed our online survey (59% female, 14 ± 10 years' experience, 73% working in an academic hospital). We inventoried (1) opinions on communication about (etiological) diagnosis, prognosis, and prevention using 11 statements; (2) current communication practices in response to five hypothetical cases (AD dementia, mild cognitive impairment (MCI), subjective cognitive decline (SCD), with ( +) or without ( -) abnormal AD biomarkers); and (3) needs for communication support regarding ten listed communication skills. RESULTS: The majority of professionals agreed that communication on diagnosis, prognosis, and prevention should be personalized to the individual patient. In response to the hypothetical patient cases, disease stage influenced the inclination to communicate an etiological AD diagnosis: 97% would explicitly mention the presence of AD to the patient with AD dementia, 68% would do so in MCI + , and 29% in SCD + . Furthermore, 58% would explicitly rule out AD in case of MCI - when talking to patients, and 69% in case of SCD - . Almost all professionals (79-99%) indicated discussing prognosis and prevention with all patients, of which a substantial part (48-86%) would personalize their communication to patients' diagnostic test results (39-68%) or patients' anamnestic information (33-82%). The majority of clinicians (79%) would like to use online tools, training, or both to support them in communicating with patients. Topics for which professionals desired support most were: stimulating patients' understanding of information, and communicating uncertainty, dementia risk, remotely/online, and with patients not (fluently) speaking the language of the country of residence. CONCLUSIONS: In a survey of European memory clinic professionals, we found a strong positive attitude towards communication with patients about (etiological) diagnosis, prognosis, and prevention, and personalization of communication to characteristics and needs of individual patients. In addition, professionals expressed a need for supporting tools and skills training to further improve their communication with patients.

Rationale and design of the ABOARD project (A Personalized Medicine Approach for Alzheimer's Disease).

The key to stopping Alzheimer's disease (AD) lies in the pre-dementia stages, with the goal to stop AD before dementia has started. We present the rationale and design of the ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) project, which aims to invest in personalized medicine for AD. ABOARD is a Dutch public-private partnership of 32 partners, connecting stakeholders from a scientific, clinical, and societal perspective. The 5-year project is structured into five work packages on (1) diagnosis, (2) prediction, (3) prevention, (4) patient-orchestrated care, and (5) communication and dissemination. ABOARD functions as a network organization in which professionals interact cross-sectorally. ABOARD has a strong junior training program "Juniors On Board." Project results are shared with society through multiple communication resources. By including relevant partners and involving citizens at risk, patients, and their care partners, ABOARD builds toward a future with personalized medicine for AD. Highlights: ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) is a public-private research project executed by 32 partners that functions as a network organization.Together, the project partners build toward a future with personalized medicine for Alzheimer's disease.Although ABOARD is a Dutch consortium, it has international relevance.ABOARD improves diagnosis, prediction, prevention, and patient-orchestrated care.

Cardiovascular Risk Management in Persons with Dementia.

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.

[A survey study towards the opinions of clinicians, patients and care partners regarding computer tools in the memory clinic: sense or nonsense?] / Een vragenlijstonderzoek naar de mening van clinici, patiënten en naasten over computertools in de geheugenpolikliniek: zin of onzin?.

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.

Determinants of informal care time, distress, depression, and quality of life in care partners along the trajectory of Alzheimer's disease.

Introduction: We evaluated determinants associated with care partner outcomes along the Alzheimer's disease (AD) stages. Methods: We included n = 270 care partners of amyloid-positive patients in the pre-dementia and dementia stages of AD. Using linear regression analysis, we examined determinants of four care partner outcomes: informal care time, caregiver distress, depression, and quality of life (QoL). Results: More behavioral symptoms and functional impairment in patients were associated with more informal care time and depressive symptoms in care partners. More behavioral symptoms were related with more caregiver distress. Spouse care partners spent more time on informal care and QoL was lower in female care partners. Behavioral problems and subtle functional impairment of the patient predisposed for worse care partner outcomes already in the pre-dementia stages. Discussion: Both patient and care partner determinants contribute to the care partner outcomes, already in early disease stages. This study provides red flags for high care partner burden.

Optimizing cCOG, a Web-based tool, to detect dementia with Lewy Bodies.

Introduction: Distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) is challenging due to overlapping presentations. We adapted a Web-based test tool, cCOG, by adding a visuospatial task and a brief clinical survey and assessed its ability to differentiate between DLB and AD. Methods: We included 110 patients (n = 30 DLB, n = 32 AD dementia, and n = 48 controls with subjective cognitive decline (SCD)). Full cCOG comprises six cognitive subtasks and a survey addressing self-reported DLB core and autonomic features. First, we compared cCOG cognitive tasks to traditional neuropsychological tasks for all diagnostic groups and clinical questions to validated assessments of clinical features in DLB only. Then, we studied the performance of cCOG cognitive tasks and clinical questions, separately and combined, in differentiating diagnostic groups. Results: cCOG cognitive tasks and clinical survey had moderate to strong correlations to standard neuropsychological testing (.61≤ r s ≤ .77) and to validated assessments of clinical features (.41≤ r s ≤ .65), except for fluctuations and REM-sleep behavior disorder (RBD) (r s = .32 and r s = .10). Full cCOG, including both cognitive tasks and brief survey had a diagnostic accuracy (acc) of 0.82 [95% CI 0.73-0.89], with good discrimination of DLB versus AD (acc 0.87 [0.76-0.95]) and DLB versus controls (acc 0.94 [0.86-0.98]). Conclusion: We illustrated that cCOG aids in distinguishing DLB and AD patients by using remote assessment of cognition and clinical features. Our findings pave the way to a funneled, harmonized diagnostic process among memory clinics and, eventually, a more timely and accurate diagnosis of DLB and AD.

Life satisfaction across the entire trajectory of Alzheimer's disease: A mediation analysis.

Introduction: We studied life satisfaction across Alzheimer's disease (AD) stages and studied mobility and meaningful activities as mediators of the associations between these AD stages and life satisfaction. Methods: In this cross-sectional study, we included n = 269 amyloid-positive patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia from the Amsterdam Dementia Cohort. Life satisfaction was measured with the satisfaction with life scale. The mediating role of transportation, work, sports, and hobbies on life satisfaction was examined in single and multiple mediator models. Results: Patients with dementia are less satisfied with life compared to SCD and MCI. These differences in life satisfaction are explained by reduced participation in meaningful activities, which in turn, was largely attributable to decreased transportation use. Discussion: Our findings suggest that improving access to transportation, therewith allowing participation in meaningful activities help to maintain life satisfaction and may be an important target for intervention.

Development and design of a diagnostic report to support communication in dementia: Co-creation with patients and care partners.

Introduction: Clear communication of diagnostic test results and dementia diagnosis is challenging yet important to empower patients and care partners. A personalized diagnostic report could support the communication of dementia diagnostics and aid patients' understanding of diagnosis. In this study, we aimed to design a diagnostic report in co-creation with patients and care partners. Methods: We used a mixed-methods approach, combining surveys with focus groups in iteration. Phase 1 consisted of an international survey assessing needs among patients (n = 50) and care partners (n = 46), and phase 2 consisted of focus group meetings (n = 3) to co-create the content and to hands-on co-design the layout of the diagnostic report with patients (n = 7) and care partners (n = 7). Phase 3 validated results from phase 2 in a survey among patients (n = 28) and care partners (n = 12), and phase 4 comprised final feedback by dementia (care) experts (n = 5). Descriptive statistics were used to report quantitative results and directed content analysis was used to analyze qualitative data. Results: Most patients (39/50, 78%) and care partners (38/46, 83%) positively valued a diagnostic report to summarize test results. The report should be brief, straightforward, and comprise results of the diagnostic tests, including brain imaging and information on future expectations. Despite a clear preference for visual display of test results, several visualization options were deemed best and were equally comprehended. Discussion: In this study, we developed a prototype of a personalized patient report through an iterative design process and learned that co-creation is highly valuable to meet the specific needs of end-users.

Sex-Specific Associations of Diabetes With Brain Structure and Function in a Geriatric Population.

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. Methods: In 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. 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. Conclusions: Diabetes 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.

Orthostatic hypotension and mortality risk in geriatric outpatients: the impact of duration and magnitude of the blood pressure drop.

INTRODUCTION: Orthostatic hypotension is a common condition associated with an increased mortality risk. This study investigates this association specifically in geriatric outpatients and additionally focuses on the duration and magnitude of orthostatic hypotension. METHODS: In this observational prospective cohort study with geriatric outpatients from the Amsterdam Ageing cohort, we differentiated orthostatic hypotension in early orthostatic hypotension (EOH) and delayed/prolonged orthostatic hypotension (DPOH). The magnitude of drop in both SBP and DBP after either 1 or 3 min was quantified. Mortality data was obtained from the Dutch municipal register. Cox proportional hazard models were used to determine the association between orthostatic hypotension and mortality, adjusted for sex and age (model 1), additionally adjusted for orthostatic hypotension-inducing drugs + SBP (model 2) and the presence of cardiovascular disease and diabetes (model 3). Stratified analyses in patients with geriatric deficits were performed. RESULTS: We included 1240 patients (mean age 79.4 ±â€Š6.9 years, 52.6% women). Prevalence of orthostatic hypotension was 443 (34.9%); 148 (11.9%) patients had EOH and 285 (23%) DPOH. DPOH was associated with a higher mortality risk [hazard ratio, 95% CI 1.69 (1.28-2.22)] whereas EOH was not associated with mortality risk. This association did not differ in patients with geriatric deficits. Furthermore, the magnitude of drop in both SBP and DBP was associated with a higher mortality risk. CONCLUSION: The presence of DPOH and the magnitude of both systolic and diastolic orthostatic hypotension are related to an increased mortality risk in geriatric outpatients. Whether the duration of orthostatic hypotension and magnitude of the drop in blood pressure is causally related to mortality risk or whether it is a sign of decreased resilience remains to be elucidated.