Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.

BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).

Enhancing cognitive performance prediction by white matter hyperintensity connectivity assessment.

White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating brain health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. Lesion network mapping (LNM) enables to infer if brain networks are connected to lesions and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed LNM to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity to 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. We compared the capacity of total and regional WMH volumes and LNM scores in predicting cognitive function using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention/executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater connectivity to WMH, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network integrity, particularly in attention-related brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients.

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.

Impact of geriatric co-management on outcomes in hospitalised cardiology patients aged 85 and over.

OBJECTIVE: Cardiovascular disease and frailty are common among the population aged 85+. We hypothesised these patients might benefit from geriatric co-management, as has been shown in other frail patient populations. However, there is limited evidence supporting geriatric co-management in older, hospitalised cardiology patients. METHODS: A retrospective cohort study was performed in a large teaching hospital in the Netherlands. We compared patients aged 85 and over admitted to the cardiology ward before (control group) and after the implementation of standard geriatric co-management (intervention group). Data on readmission, mortality, length of stay, number of consultations, delirium, and falls were analysed. RESULTS: The data of 1163 patients were analysed (n = 542 control, n = 621 intervention). In the intervention group, 251 patients did not receive the intervention because of logistic reasons or the treating physician's decision. Baseline characteristics were comparable in the intervention and control groups. Patients in the intervention group had a shorter length of stay (-1 day, p = 0.01) and were more often discharged to a geriatric rehabilitation facility (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.10-3.54, p = 0.02) compared with the control patients. Other outcomes were not significantly different between the groups. CONCLUSIONS: After implementation of standard geriatric co-management for hospitalised cardiology patients aged 85 and over, the length of hospital stay shortened and the number of patients discharged to a geriatric rehabilitation facility increased. The adherence to geriatric team recommendations was high. Geriatric co-management would appear to optimise care for older hospitalised patients with cardiac disease.

Psychosocial factors and hippocampal subfields: The Medea-7T study.

Specific subfields within the hippocampus have shown vulnerability to chronic stress, highlighting the importance of looking regionally within the hippocampus to understand the role of psychosocial factors in the development of neurodegenerative diseases. A systematic review on psychosocial factors and hippocampal subfield volumes was performed and showed inconsistent results, highlighting the need for future studies to explore this relationship. The current study aimed to explore the association of psychosocial factors with hippocampal (subfield) volumes, using high-field 7T MRI. Data were from the Memory Depression and Aging (Medea)-7T study, which included 333 participants without dementia. Hippocampal subfields were automatically segmented from T2-weighted images using ASHS software. Generalized linear models accounting for correlated outcomes were used to assess the association between subfields (i.e., entorhinal cortex, subiculum, Cornu Ammonis [CA]1, CA2, CA3, dentate gyrus, and tail) and each psychosocial factor (i.e., depressive symptoms, anxiety symptoms, childhood maltreatment, recent stressful life events, and social support), adjusted for age, sex, and intracranial volume. Neither depression nor anxiety was associated with specific hippocampal (subfield) volumes. A trend for lower total hippocampal volume was found in those reporting childhood maltreatment, and a trend for higher total hippocampal volume was found in those who experienced a recent stressful life event. Among subfields, low social support was associated with lower volume in the CA3 (B = -0.43, 95% CI: -0.72; -0.15). This study suggests possible differential effects among hippocampal (subfield) volumes and psychosocial factors.

Basal ganglia calcifications: No association with cognitive function.

BACKGROUND AND PURPOSE: Basal ganglia calcifications (BGC), a form of vascular calcification, are a common brain computed tomography (CT) finding. We investigated whether BGC are associated with cognitive function and examined the association between vascular risk factors and BGC. MATERIAL AND METHODS: Patients who visited a memory clinic of a Dutch general hospital between April 2009 and April 2015 were included. The patients underwent a standard diagnostic work up including cognitive tests (Cambridge Cognitive Examination, including the Mini Mental State Examination) and brain CT. Vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia and smoking were assessed. CTs were analyzed for presence and severity (absent, mild, moderate or severe) of BGC. Multivariable logistic regression was used to identify risk factors for BGC and linear regression for the association between BGC and cognitive function. RESULTS: Of the 1992 patients, 40.3% was male. The median age was 80 years and 866 patients (43.5%) had BGC. BGC was associated with female gender (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06-1.53, p 0.011), and inversely associated with hypertension (OR 0.74, 95% CI 0.60-0.89, p 0.002) and use of antihypertensive drugs (OR 0.79, 95% CI 0.64-0.98, p 0.031). No association was found between presence and severity of BGC and cognitive function or other vascular risk factors. CONCLUSIONS: No association with cognitive function was found. Risk factors for BGC were female gender, while hypertension and antihypertensive drug use were associated with a lower risk of BGC.

The impact of frailty on adverse outcomes after transcatheter aortic valve replacement in older adults: A retrospective cohort study.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement for patients who are at increased surgical risk. Consequently, frailty is common in patients undergoing TAVR. OBJECTIVES: This study aims to investigate the impact of frailty on outcomes following TAVR. METHODS: A retrospective cohort study was conducted, including all TAVR candidates who visited the geriatric outpatient clinic for preoperative screening. Frailty status was assessed according to the Groningen Frailty Indicator. The primary outcome of the study was defined as the occurrence of postoperative complications, and this was evaluated according to the Clavien-Dindo classification. An additional analysis was performed to assess the impact of frailty on 1-year all-cause mortality and complications within 30 days of TAVR according to the Valve Academic Research Consortium (VARC-2) criteria. The VARC-2 criteria provide harmonized endpoint definitions for TAVR studies. RESULTS: In total, 431 patients with a mean age of 80.8 ± 6.2 years were included, of whom 56% were female. Frailty was present in 36% of the participants. Frailty was associated with a higher risk of the composite outcome of complications [adjusted odds ratio (OR): 1.55 (95% confidence interval, CI: 1.03-2.34)], 30-day mortality [adjusted OR: 4.84 (95% CI: 1.62-14.49)], 3-month mortality [adjusted OR: 2.52 (95% CI: 1.00-6.28)] and 1-year mortality [adjusted OR: 2.96 (95% CI: 1.46-6.00)]. CONCLUSIONS: Frailty is common in TAVR patients and is associated with an increased overall risk of postoperative complications, particularly mortality. Increased optimization of screening and treatment of frailty in the guidelines for valvular heart diseases is recommended.

Prevalence and Association of Basal Ganglia Calcifications and Depressive Symptoms in Patients With Mild Cognitive Impairment or Dementia.

AIM: The aim of this study is to investigate the association between basal ganglia calcification (BGC) and depressive symptoms within older adults with mild cognitive impairment (MCI) or dementia. METHODS: For this cross-sectional study, we included patients with MCI or dementia who visited the memory clinic between April 2009 and April 2015. All patients underwent a standard diagnostic workup, including assessment of depressive symptoms with the Geriatric Depression Scale and computed tomography imaging of the brain. Computed tomography scans were assessed for presence and severity of BGC. To analyse the association between BGC and depressive symptoms, binary logistic regression models were performed with adjustment for age, sex, cardiovascular risk factors, and cardiovascular diseases. RESULTS: In total, 1054 patients were included (median age: 81.0 y; 39% male). BGC was present in 44% of the patients, of which 20% was classified as mild, 20% as moderate, and 4% as severe. There were 223 patients (21%) who had a Geriatric Depression Scale score indicative of depressive symptoms. No association was found between the presence or severity of BGC and depressive symptoms. CONCLUSIONS: Although both BGC and depressive symptoms were common in patients with MCI or dementia, no association was demonstrated between the presence or severity of BGC and depressive symptoms.

Intracranial artery calcifications: Risk factors and association with cardiovascular disease and cognitive function.

BACKGROUND AND AIMS: we know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function. METHODS: patients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination. RESULTS: 1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p < 0.001), diabetes mellitus (medial iICA, p = 0.004), hypertension (intimal iICA, p < 0.001) and basilar artery, p = 0.019) and smoking (intimal iICA, p = 0.008). iICA calcifications were associated with stroke and intimal calcifications also with myocardial infarction. Intracranial artery calcifications were not associated with cognitive function or type of cognitive disorder. CONCLUSION: the majority of memory clinic patients had intracranial artery calcifications. Cardiovascular risk factors are differentially related to medial or intimal iICA calcifications. iICA calcifications were associated with myocardial infarction and stroke, but not with cognitive outcomes.

Statins After Ischemic Stroke in the Oldest: A Cohort Study Using the Clinical Practice Research Datalink Database.

[Figure: see text].

Histology and computed tomography of incidental calcifications in the human basal ganglia.

Incidental basal ganglia calcifications are a common finding on computed tomography (CT). We investigated the histological characteristics of these calcifications and their association with CT findings, using post-mortem basal ganglia tissue from 22 patients. Eight patients had basal ganglia calcifications on histology, and six patients had calcifications on CT, varying from mild to severe. Four patients had calcifications identified by both histology and CT, and two patients had calcifications detected by CT but not by histology, possibly because of insufficient tissue available. Calcifications were found mainly in the tunica media of arterioles located in the globus pallidus, which suggests that incidental CT calcifications are vascular in nature. However, tunica media calcifications, and thereby incidental basal ganglia calcifications, are probably not related to atherosclerosis.

Risk factors for calcification of the vertebrobasilar arteries in cardiovascular patients referred for a head CT, the SMART study.

BACKGROUND AND PURPOSE: Vertebrobasilar artery calcification (VBAC) has been associated with increased stroke occurrence. Little is known on VBAC risk factors, especially for patients with cardiovascular disease. We aimed to assess risk factors associated with VBAC in a cohort of cardiovascular patients referred for a head computed tomography (CT) scan. MATERIALS AND METHODS: All patients who underwent a clinically indicated, unenhanced, thin slice head CT 6 months before or after inclusion in the SMART study were included. CTs were assessed for presence of VBAC (dichotomously). Relative risks of the associations of age, sex, diabetes mellitus (DM), obesity, body mass index, estimated glomerular filtration rate, hypertension, hyperlipidemia, use of lipid lowering medication, smoking status, high sensitivity C-reactive protein, ankle-brachial index (ABI; ≤0.90, ≥1.30, continuous), internal carotid artery stenosis ≥70%, and carotid intima-media thickness (IMT) with VBAC were estimated using Poisson regression analysis with robust standard errors, adjusted for age and sex. RESULTS: Of the 471 patients included (57% male, median age 58 [interquartile range 47-63]), 117 (24.8%) showed VBAC. Presence of VBAC was associated with older age (RR per 10 years=1.70 [95%CI 1.46-1.99]), DM (RR=1.45 [95%CI 1.03-2.06]), obesity (RR=1.53 [95%CI 1.10-2.12]), ABI ≤0.90 (RR=1.57 [95%CI 1.02-2.41]), and an increased carotid IMT (RR=2.60 per mm [95%CI 1.20-5.62]). Other measurements were not associated with VBAC. CONCLUSIONS: We identified several markers associated with VBAC in patients with cardiovascular disease referred for a head CT. Future investigation into the relationship between VBAC and stroke is warranted to determine the potential of VBAC in stroke prevention.

The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum.

OBJECTIVE: To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. METHODS: Data from two large cohort studies, the Dutch Parelsnoer Institute - Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N = 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of Aß42, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. RESULTS: Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF Aß42, higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF Aß42 and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. CONCLUSION: The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.

Risk factors of mortality in older patients with dementia in psychiatric care.

OBJECTIVE: To examine the mortality risk, and its risk factors, of older patients with dementia in psychiatric care. METHODS: We constructed a cohort of dementia patients through data linkage of four Dutch registers: the Psychiatric Case Register Middle Netherlands (PCR-MN), the hospital discharge register, the population register, and the national cause of death register. All dementia patients in PCR-MN aged between 60 and 100 years between 1 January 2000 and 31 December 2010 were included. Risk factors of mortality were investigated using Cox proportional hazard regression models with adjustment for age, sex, setting of care, nationality, marital status, dementia type, and psychiatric and somatic comorbidities. RESULTS: In total, 4297 patients were included with a median age of 80 years. The 1-year, 3-year, and 5-year mortality were 16.4%, 44.4%, and 63.5%, respectively. Determinants that increased the 1-year mortality were: male sex (adjusted hazard ratio [HR]: 1.49; 95% confidence interval [95% CI], 1.26-1.76), higher age (HR 1.08; 95% CI, 1.07-1.09), inpatient psychiatric care (HR 1.52; 95% CI, 1.19-1.93), more somatic comorbidities (HR 1.67; 95% CI, 1.49-1.87), and cardiovascular disease separately (HR 1.54; 95% CI, 1.30-1.82). Results for 3-year and 5-year mortality were comparable. Living together/married increased the 3- and 5-year mortality, and Dutch nationality increased the 5-year mortality. There were no differences in mortality with different types of psychiatric comorbidity. CONCLUSION: Mortality of dementia patients in psychiatric care was high, much higher than mortality in the general older population. The results of this study should raise awareness about their unfavourable prognosis, particularly older patients, men, inpatients, and patients with more somatic comorbidity.

A prediction model for one- and three-year mortality in dementia: results from a nationwide hospital-based cohort of 50,993 patients in the Netherlands.

OBJECTIVE: to develop a model to predict one- and three-year mortality in patients with dementia attending a hospital, through hospital admission or day/memory clinic. DESIGN: we constructed a cohort of dementia patients through data linkage of three Dutch national registers: the hospital discharge register (HDR), the population register and the national cause of death register. SUBJECTS: patients with dementia in the HDR aged between 60 and 100 years registered between 1 January 2000 and 31 December 2010. METHODS: logistic regression analysis techniques were used to predict one- and three-year mortality after a first hospitalisation with dementia. The performance was assessed using the c-statistic and the Hosmer-Lemeshow test. Internal validation was performed using bootstrap resampling. RESULTS: 50,993 patients were included in the cohort. Two models were constructed, which included age, sex, setting of care (hospitalised versus day clinic) and the presence of comorbidity using the Charlson comorbidity index. One model predicted one-year mortality and the other three-year mortality. Model discrimination according to the c-statistic for the models was 0.71 (95% CI 0.71-0.72) and 0.72 (95% CI 0.72-0.73), respectively. CONCLUSION: both models display acceptable ability to predict mortality. An important advantage is that they are easy to apply in daily practise and thus are helpful for individual decision-making regarding diagnostic/therapeutic interventions and advance care planning.

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients.

INTRODUCTION: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations. METHODS: We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures. RESULTS: SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant. DISCUSSION: In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.

Prevalence and vascular risk factors of basal ganglia calcifications in patients at risk for cerebrovascular disease.

BACKGROUND AND PURPOSE: Risk factors for and meaning of basal ganglia calcifications outside Fahr syndrome are poorly understood. We aimed to assess the prevalence of basal ganglia calcifications and the association with vascular risk factors. MATERIALS AND METHODS: 1133 patients suspected of acute ischemic stroke from the Dutch acute stroke (DUST) study who underwent thin-slice unenhanced brain CT were analyzed. Basal ganglia calcifications were scored bilaterally as absent, mild (dot), moderate (multiple dots or single artery) and severe (confluent). Uni- and multivariable logistic regression analysis was used to determine possible risk factors (age, gender, history of stroke, smoking, hypertension, diabetes mellitus, hyperlipidemia, body mass index (BMI), renal function and family history of cardiovascular disease under 60 years) for presence of basal ganglia calcifications and ordinal regression analysis for severity of basal ganglia calcifications. RESULTS: Mean age was 67.4 years (SD: 13.8), 56.8% were male. 337 (29.7%) patients had basal ganglia calcifications, of which 196 (58%) were mild, 103 (31%) moderate, 38 (11%) severe. In multivariable logistic regression analysis, age (OR: 1.02, 95% CI 1.01-1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.91-0.98, p 0.01) were significantly associated with the presence of basal ganglia calcifications. Ordinal regression analysis gave comparable results. Age (OR: 1.02, 95% CI 1.01-1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.92-0.99, P 0.01) were significantly associated with severity of basal ganglia calcifications. CONCLUSIONS: In this study with patients suspected of acute ischemic stroke, basal ganglia calcifications were common and significantly associated with older age and lower BMI.

Increased mortality and hospital readmission risk in patients with dementia and a history of cardiovascular disease: Results from a nationwide registry linkage study.

OBJECTIVE: To evaluate the impact of cardiovascular disease (CVD) on mortality and readmission risk in patients with dementia. METHODS: Prospective hospital-based cohort of 59 194 patients with dementia admitted to hospital or visiting a day-clinic between 2000 and 2010. Patients were divided in those with and without a history of CVD (ie, previous admission for CVD; coronary heart disease, heart failure, stroke, atrial fibrillation, or other CVD). Absolute mortality risks (ARs), median survival times, and hazard ratios (adjusted for age, sex, and comorbidity) were calculated. RESULTS: Three-year ARs and HRs were higher, and survival times were shorter among patients visiting a day-clinic with a history of CVD than in those without. The differences were less pronounced for inpatients. Readmission risk was further increased in the presence of CVD in both day clinic and inpatients. CONCLUSION: Clinicians need to be more aware of worse prognosis of the population with CVD and dementia.

Hippocampal Calcifications: Risk Factors and Association with Cognitive Function.

Purpose To identify risk factors for hippocampal calcifications and to investigate the association between hippocampal calcifications and cognitive function. Materials and Methods For this retrospective study, consecutive patients visiting a memory clinic at a Dutch general hospital between April 2009 and April 2015 were identified. All individuals underwent a standard diagnostic work-up including cognitive tests and brain CT. The following vascular risk factors were assessed: hypertension, diabetes mellitus, hyperlipidemia, and smoking. Cognitive screening consisted of the Cambridge Cognitive Examination, which includes the Mini-Mental State Examination. CT scans were analyzed for the presence and severity (absent, mild, moderate, severe) of hippocampal calcifications. One measure per patient, only the most severe score, was used. Logistic regression was used to identify risk factors for hippocampal calcifications, and linear regression was used for the association between hippocampal calcifications (patient level) and cognitive function. Results A total of 1991 patients (mean age, 78 years; range, 45-96 years) were included. The mean age of women was 79 years (range, 47-96 years), and the mean age of men was 77 years (range, 45-95 years). Of the 1991 patients, 380 (19.1%) had hippocampal calcifications. Older age (odds ratio [OR] per year, 1.05; 95% confidence interval [CI]: 1.03, 1.06), diabetes mellitus (OR, 1.50; 95% CI: 1.12, 2.00), and smoking (OR, 1.49; 95% CI: 1.05, 2.10) were associated with the presence of hippocampal calcifications. No associations were found between presence and severity of hippocampal calcifications and cognitive function. Conclusion Older age, diabetes mellitus, and smoking were associated with an increased risk of hippocampal calcifications. A greater degree of hippocampal calcifications was not associated with lower cognitive function in patients with memory complaints.

Hippocampal calcification on brain CT: prevalence and risk factors in a cerebrovascular cohort.

OBJECTIVES: Recently, hippocampal calcification as observed on brain CT examinations was identified in over 20% of people over 50 years of age and a relation between hippocampal calcification and cognitive decline was shown. We determined the prevalence and investigated the vascular risk factors of hippocampal calcification in patients with cerebrovascular disease. METHODS: Hippocampal calcification was scored bilaterally on presence and severity on CT examinations in a cohort of 1130 patients with (suspected) acute ischaemic stroke. Multivariable logistic regression analysis, adjusting for age and gender as well as adjusting for multiple cardiovascular disease risk factors, was used to determine risk factors for hippocampal calcification. RESULTS: Hippocampal calcification was present in 381 (34%) patients. Prevalence increased with age from 8% below 40 to 45% at 80 years and older. In multivariable logistic regression analysis, age per decile (OR 1.41 [95% CI 1.26-1.57], p < 0.01), hypertension (OR 0.74 [95% CI 0.56-0.99], p = 0.049), diabetes mellitus (OR 1.57 [95% CI 1.10-2.25], p = 0.01) and hyperlipidaemia (OR 1.63 [95% CI 1.20-2.22], p < 0.01) were significantly associated with hippocampal calcification. CONCLUSIONS: Hippocampal calcification was a frequent finding on CT in this cohort of stroke patients and was independently positively associated with hyperlipidaemia and diabetes mellitus, suggesting an atherosclerotic origin. KEY POINTS: • Hippocampal calcification is prevalent in over 30% of cerebrovascular disease patients. • Prevalence increases from 8% below 40 to 45% over 80 years. • Hippocampal calcification is associated with cardiovascular risk factors hyperlipidaemia and diabetes mellitus.