Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using a smartphone PPG app: the Dutch-GERAF study.

BACKGROUND: Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). METHODS: This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65 years and the ability to perform at least three PPG recordings within 6 months. Exclusion criteria are the presence of a cardiac implantable device, advanced dementia or a severe tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after a positive PPG recording, a confirmatory electrocardiogram is performed. Patients undergo a comprehensive geriatric assessment and a frailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6 months, 12 months and 3 years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality. DISCUSSION: The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population. TRIAL REGISTRATION: NCT05337202.

The Use of Oral Anticoagulation Is Not Independently Associated with Mortality in Frail Older Patients with Repeated Falls.

BACKGROUND: Particularly in frail patients, anticoagulation may be underused because of the fear of bleeding. OBJECTIVE: To determine whether the use of antithrombotic medication is an independent risk factor for mortality in frail elderly with repeated falls. METHODS: All patients aged 65 years or older at the Fall and Syncope Clinic were eligible. Frailty was calculated with a Frailty Index (FI) based on the accumulation of deficits model. Risks were calculated with a cox regression analysis, adjusted for age, sex, and Frailty Index. RESULTS: 663 patients were included in this analysis. The median age was 80 years, 438 were women (66%), 73% had polypharmacy, and 380 patients (57%) had cognitive impairment. The mean FI was 0.23 (sd 0.09), 182 patients were moderately frail (27.5%), and 259 (39.1%) were severely frail. A total of 140 (21%) used oral anticoagulation and 223 (34%) used antiplatelet agents. A total of 196 patients (29.6%) died during follow-up. In the adjusted cox regression model, the use of neither antiplatelets nor anticoagulation was associated with mortality. A strong association was found with frailty (HR 74.0, 95% CI 13.1-417.3) and a weak association with age (HR 1.05, 95% CI 1.03-1.08). A lower risk of mortality was seen in women (HR 0.5, 95% CI 0.3-0.6). CONCLUSIONS: In this cohort of frail older patients, there was no independent association between the use of antithrombotic medication and mortality. A strong association with mortality was found with frailty, a weak association was found with age, and a lower mortality risk was found in women. Our data indicate that the fear of bleeding or increased mortality in frail patients with an indication for oral anticoagulation may be unjustified.

Does atrial fibrillation affect prognosis in hospitalised COVID-19 patients? A multicentre historical cohort study in the Netherlands.

OBJECTIVES: The aim of this multicentre COVID-PREDICT study (a nationwide observational cohort study that aims to better understand clinical course of COVID-19 and to predict which COVID-19 patients should receive which treatment and which type of care) was to determine the association between atrial fibrillation (AF) and mortality, intensive care unit (ICU) admission, complications and discharge destination in hospitalised COVID-19 patients. SETTING: Data from a historical cohort study in eight hospitals (both academic and non-academic) in the Netherlands between January 2020 and July 2021 were used in this study. PARTICIPANTS: 3064 hospitalised COVID-19 patients >18 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the incidence of new-onset AF during hospitalisation. Secondary outcomes were the association between new-onset AF (vs prevalent or non-AF) and mortality, ICU admissions, complications and discharge destination, performed by univariable and multivariable logistic regression analyses. RESULTS: Of the 3064 included patients (60.6% men, median age: 65 years, IQR 55-75 years), 72 (2.3%) patients had prevalent AF and 164 (5.4%) patients developed new-onset AF during hospitalisation. Compared with patients without AF, patients with new-onset AF had a higher incidence of death (adjusted OR (aOR) 1.71, 95% CI 1.17 to 2.59) an ICU admission (aOR 5.45, 95% CI 3.90 to 7.61). Mortality was non-significantly different between patients with prevalent AF and those with new-onset AF (aOR 0.97, 95% CI 0.53 to 1.76). However, new-onset AF was associated with a higher incidence of ICU admission and complications compared with prevalent AF (OR 6.34, 95% CI 2.95 to 13.63, OR 3.04, 95% CI 1.67 to 5.55, respectively). CONCLUSION: New-onset AF was associated with an increased incidence of death, ICU admission, complications and a lower chance to be discharged home. These effects were far less pronounced in patients with prevalent AF. Therefore, new-onset AF seems to represent a marker of disease severity, rather than a cause of adverse outcomes.

To STOPP or to START? Potentially inappropriate prescribing in older patients with falls and syncope.

OBJECTIVES: To investigate the prevalence of potentially inappropriate prescribing (PIP) according to the revised STOPP/START criteria in older patients with falls and syncope. STUDY DESIGN: We included consecutive patients with falls and syncope aged ≥65 years at the day clinic of the Northwest Clinics, the Netherlands, from 2011 to 2016. All medication use before and after the visit was retrospectively investigated using the revised STOPP/START criteria. MAIN OUTCOME MEASURES: The prevalence/occurrence of PIP before the visit, persistent PIP after the visit, and unaddressed persistent PIP not explained in the patient's chart. RESULTS: PIP was present in 98 % of 374 patients (mean age 80 (SD ±â€¯7) years; 69 % females). 1564 PIP occurrences were identified. 1015 occurrences persisted (in 91 % of patients). 690 occurrences (in 80 % of patients) were not explained in the patient's chart. The most frequent unaddressed persistent forms of PIP were prescriptions of vasodilator drugs for patients with orthostatic hypotension (16 %), and benzodiazepines for >4 weeks (10 %) or in fall patients (8 %), and omission of vitamin D (28 %), antihypertensive drugs (24 %), and antidepressants (17 %). 54 % of all medication changes were initiated for reasons beyond the scope of the STOPP/START criteria. CONCLUSIONS: Almost every patient in our study population suffered from PIP. In 80 %, PIP continued after the clinical visit, without an explanation in the patient's chart. The most frequent PIP concerned medication that increased the risk of falls or syncope, specifically vasodilator drugs and benzodiazepines. Physicians should be aware of PIP in older patients with falls and syncope. Further studies should investigate whether a structured medication review may improve clinical outcomes.

The trajectory of C-reactive protein serum levels in older hip fracture patients with postoperative delirium.

OBJECTIVES: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. METHODS: This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C-reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. RESULTS: Forty-one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1-2 days) and more prolonged delirium (3 days or more). CONCLUSIONS: Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory-vascular) pathological pathway of postoperative delirium.

Different patterns of orthostatic hypotension in older patients with unexplained falls or syncope: orthostatic hypotension patterns in older people.

PURPOSE: To evaluate different patterns of orthostatic hypotension (OH) and its relation to mortality in older patients with unexplained falls or syncope. METHODS: This is an observational cohort study in consecutive patients aged ≥ 65 years with unexplained falls or syncope at a Fall Syncope day clinic November 2011 until May 2016. OH is defined as a decrease in systolic blood pressure (BP) ≥ 20 mmHg and/or in diastolic BP ≥ 10 mmHg during standing test. Main outcomes are the baseline characteristics and prevalence of patients with classical OH (decrease BP until 3 min), delayed OH (decrease of BP from 5 to 10 min) and continuous OH (decrease of BP for 10 min). Secondary outcome is the relation between different OH patterns and mortality. RESULTS: Of 374 patients with a mean age of 80 year (SD 6.6), 56% of the patients had OH: 16% had classical OH, 8% delayed OH, 32% had continuous OH and 44% had no OH. Patients with continuous OH and patients with delayed OH tended to have a higher mortality compared to patients with classical OH, 14 vs. 5% (P = 0.07) and 17 vs. 5% (P = 0.06). This possible relation between OH patterns and mortality could not be confirmed in multivariate analysis. CONCLUSIONS: In these very old patients, there are various patterns of decline in standing BP. Delayed and continuous OH will be missed if BP is measured only for 3 min during standing. This is important because patients with continuous OH and delayed OH might have a relation with mortality. Our results encourage additional studies investigating the relation between different OH patterns and mortality.

Multiple causes of syncope in the elderly: diagnostic outcomes of a Dutch multidisciplinary syncope pathway.

Aims: To assess the diagnostic outcomes of a multidisciplinary pathway for elderly syncope patients. Methods and results: Observational cohort study at a Fall and Syncope Clinic, including consecutive syncope patients aged ≥65 years between 2011 and 2014. Measurements: The sort, number, and accuracy of diagnoses resulting in syncope. Secondary outcomes: reliability of the medical history and the number of electrocardiogram (ECG) abnormalities. The 117 included patients (72% females) had a mean age of 80 ± 6.5 years and a mean of 11 ± 5 (mainly cardiovascular) comorbidities. We found 212 contributing diagnoses. Symptomatic orthostatic/postprandial hypotension was present in 45%, cardiac causes in 44% (rhythm or conduction disorders 24%, aortic stenosis 4%, cardiomyopathies 2%, suspected cardiac causes 15%), and reflex syncope in 21%; 6% remained without any explanation. The diagnosis of the cause of syncope was uncertain in 34.2%, probable in 15.4%, and definite/most likely in 50.4%. Cognitive impaired patients were less likely to give a reliable medical history regarding their syncope (72% vs. 98% in cognitive intact patients, P = 0.001). In only 25% of patients a useful eyewitness account was available. 64% of ECGs showed relevant abnormalities; 26% was suggestive of cardiac syncope, of which 20% showed an indication for device implantation. Conclusion: The majority of our elderly syncope patients had multiple contributing factors, often in addition to their primary diagnosis. Orthostatic/postprandial hypotension and cardiac disorders were the most frequent. Using a multidisciplinary approach, one or more possible explanations for the syncope were found in 94% of patients, with a definite diagnosis in 50%.

Cognitive Impairment Is Very Common in Elderly Patients With Syncope and Unexplained Falls.

OBJECTIVES: To evaluate the prevalence of cognitive impairment (CI), including mild CI and dementia, in elderly patients with syncope and unexplained falls. In this population, we compared the use of the Mini-Mental State Examination (MMSE) with a cognitive screening test that assesses executive dysfunction typical of subcortical (vascular) CI, that is, the Montreal Cognitive Assessment (MoCA). DESIGN: Observational cohort study. SETTING: Outpatient fall and syncope clinic. PARTICIPANTS: Consecutive patients aged ≥65 years with syncope and unexplained falls without loss of consciousness. MEASUREMENTS: Baseline characteristics, functional status, MMSE, MoCA, and magnetic resonance imaging scans of the brain. MAIN OUTCOME: prevalence of CI, comparing the MMSE with the MoCA. CI was defined as an MMSE/MoCA score <26. SECONDARY OUTCOMES: MMSE/MoCA overall and subdomain scores, Fazekas and medial temporal lobe atrophy scores. RESULTS: We included 200 patients, mean age 79.5 (standard deviation 6.6) years (Syncope Group: n = 101; Fall Group: n = 99). Prevalence of CI was 16.8% (MMSE) versus 60.4% (MoCA) in the Syncope Group (P < .001) and 16.8% (MMSE) versus 56.6% (MoCA) in the Fall Group (P < .001). Prevalence of CI did not differ between the Syncope Group and Fall Group with either method. Executive dysfunction was present in both groups. CONCLUSION: CI is as common in elderly patients with syncope as it is in patients with unexplained falls, with an overall prevalence of 58%. The MMSE fails as a screening instrument for CI in these patients, because it does not assess executive function. Therefore, we recommend the MoCA for cognitive screening in older patients with syncope and unexplained falls.

Validation and psychometric properties of the Delirium Motor Subtype Scale in elderly hip fracture patients (Dutch version).

The Delirium Motor Subtype Scale (DMSS) was developed to capture all the previous different approaches to delirium motor subtyping into one new instrument and emphasize disturbances of motor activity rather than associated psychomotoric symptoms. We investigated reliability and validity of the DMSS Dutch version. Elderly patients who had undergone hip fracture surgery received the DMSS and the Delirium Rating Scale Revised-98 (DRS-R-98). A diagnosis of delirium was defined according to the Confusion Assessment Method (CAM). Among 146 patients, 46 (32%) patients were diagnosed with delirium (mean age 86.3 years; SD 5.2). The internal consistency of the DMSS was acceptable (Cronbach's alpha=0.72). If an item was removed at random the internal consistency of the scale remained the same. Similarly the concurrent validity of DMSS was good (Cohen's kappa=0.73) while for each motor subtype the Cohen's kappa ranged from 0.58 to 0.85. The sensitivity and specificity of DMSS to detect each subtype ranged from 0.56 to 1 and from 0.88 to 0.98, respectively. This study suggests that the Dutch version of the DMSS is a reliable and valid instrument. The DMSS has scientific validity that could allow for greater precision in further research on motor subtypes.

The neuropsychological sequelae of delirium in elderly patients with hip fracture three months after hospital discharge.

BACKGROUND: Delirium is a risk factor for long-term cognitive impairment and dementia. Yet, the nature of these cognitive deficits is unknown as is the extent to which the persistence of delirium symptoms and presence of depression at follow-up may account for the association between delirium and cognitive impairment at follow-up. We hypothesized that inattention, as an important sign of persistent delirium and/or depression, is an important feature of the cognitive profile three months after hospital discharge of patients who experienced in-hospital delirium. METHODS: This was a prospective cohort study. Fifty-three patients aged 75 years and older were admitted for surgical repair of acute hip fracture. Before the surgery, baseline characteristics, depressive symptomatology, and global cognitive performance were documented. The presence of delirium was assessed daily during hospital admission and three months after hospital discharge when patients underwent neuropsychological assessment. RESULTS: Of 27 patients with in-hospital delirium, 5 were still delirious after three months. Patients with in-hospital delirium (but free of delirium at follow-up) showed poorer performance than patients without in-hospital delirium on tests of global cognition and episodic memory, even after adjustment for age, gender, and baseline cognitive impairment. In contrast, no differences were found on tests of attention. Patients with in-hospital delirium showed an increase of depressive symptoms after three months. However, delirium remained associated with poor performance on a range of neuropsychological tests among patients with few or no signs of depression at follow-up. CONCLUSION: Elderly hip fracture patients with in-hospital delirium experience impairments in global cognition and episodic memory three months after hospital discharge. Our results suggest that inattention, as a cardinal sign of persistent delirium or depressive symptomatology at follow-up, cannot fully account for the poor cognitive outcome associated with delirium.

Delirium motor subtypes in elderly hip fracture patients: risk factors, outcomes and longitudinal stability.

OBJECTIVE: Delirium is often accompanied by changes in motor activity but the longitudinal expression of these features and etiological and prognostic significance of clinical subtypes defined by motor activity is unclear. METHODS: This is a prospective cohort study of elderly patients undergoing hip fracture surgery. Baseline characteristics were assessed preoperatively. During hospital admission presence of delirium was assessed daily according to CAM criteria. This study compared baseline characteristics and outcomes according to a longitudinal pattern of motor subtype expression (predominantly hyperactive, predominantly hypoactive, predominantly mixed, no motor subtype and variable). Motor subtype categorization was performed with the DRS-R98. We also investigated the longitudinal stability of motor subtypes across the delirium episode. RESULTS: 62 patients had experienced in-hospital delirium postoperatively. The full course of the delirium episode could be defined for 42/62 (67.7%) patients. Of the patients with multiple days of delirium only 4/30 (13.3%) patients had a consistent motor subtype profile throughout the delirium episode, while 26/30 (86.7%) patients had a variable course. Of the patients with multiple days of delirium, 5/30 (16.7%) were predominantly hypoactive in profile, 7/30 (23.3%) predominantly hyperactive, 6/30 (20%) predominantly mixed, 1/30 (3.3%) had no motor subtype and 11/30 (36.7%) had a variable profile. Baseline characteristics and outcomes did not differ between the groups. CONCLUSION: The majority of elderly hip fracture patients in this homogenous sample experienced variable expression of motor subtype over the course of their delirium episodes. The subtype categorization according to dominant motor subtype across the delirium episode identified groups with similar characteristics and outcomes.

Predicting delirium duration in elderly hip-surgery patients: does early symptom profile matter?

Background. Features that may allow early identification of patients at risk of prolonged delirium, and therefore of poorer outcomes, are not well understood. The aim of this study was to determine if preoperative delirium risk factors and delirium symptoms (at onset and clinical symptomatology during the course of delirium) are associated with delirium duration. Methods. This study was conducted in prospectively identified cases of incident delirium. We compared patients experiencing delirium of short duration (1 or 2 days) with patients who had more prolonged delirium (≥3 days) with regard to DRS-R-98 (Delirium Rating Scale Revised-98) symptoms on the first delirious day. Delirium symptom profile was evaluated daily during the delirium course. Results. In a homogenous population of 51 elderly hip-surgery patients, we found that the severity of individual delirium symptoms on the first day of delirium was not associated with duration of delirium. Preexisting cognitive decline was associated with prolonged delirium. Longitudinal analysis using the generalised estimating equations method (GEE) identified that more severe impairment of long-term memory across the whole delirium episode was associated with longer duration of delirium. Conclusion. Preexisting cognitive decline rather than severity of individual delirium symptoms at onset is strongly associated with delirium duration.

Affective functioning after delirium in elderly hip fracture patients.

BACKGROUND: Delirium in elderly patients is associated with various long-term sequelae that include cognitive impairment and affective disturbances, although the latter is understudied. METHODS: For a prospective cohort study of elderly patients undergoing hip fracture surgery, baseline characteristics and affective and cognitive functioning were assessed preoperatively. During hospital admission, presence of delirium was assessed daily. Three months after hospital discharge, affective and global cognitive functioning was evaluated again in patients free from delirium at the time of this follow-up. This study compared baseline characteristics and affective functioning between patients with and without in-hospital delirium. We investigated whether in-hospital delirium is associated with increased anxiety and depressive levels, and post-traumatic stress disorder (PTSD) symptoms three months after discharge. RESULTS: Among 53 eligible patients, 23 (43.4%) patients experienced in-hospital delirium after hip fracture repair. Patients who had experienced in-hospital delirium showed more depressive symptoms at follow-up after three months compared to the 30 patients without in-hospital delirium. This association persisted in a multivariate model controlling for age, baseline cognition, baseline depressive symptoms, and living situation. The level of anxiety and symptoms of PTSD at follow-up did not differ between both groups. CONCLUSION: This study suggests that in-hospital delirium is associated with an increased burden of depressive symptoms three months after discharge in elderly patients who were admitted to the hospital for surgical repair of hip fracture. Symptoms of depression in patients with previous in-hospital delirium cannot be fully explained by persistent (sub)syndromal delirium or baseline cognitive impairment.

Cortical oxygen supply during postural hypotension is further decreased in Alzheimer's disease, but unrelated to cholinesterase-inhibitor use.

Cerebrovascular function and structure of the cortical cerebral microvessels are profoundly altered in patients with Alzheimer's disease (AD). The functional hemodynamic consequences of such changes, however, remain essentially unknown. Cholinesterase inhibitors (ChEIs) potentially affect brain perfusion through either augmentation or inhibition of cerebral vasodilatation. This study investigated the cerebrovascular regulation during postural changes in AD before and after treatment with the ChEI galantamine. In 21 AD patients and 20 controls, blood pressure (BP--Finapres), frontal cortical oxygenation (near-infrared-spectroscopy), and cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography) were measured following a hypotensive challenge induced by postural change. In AD, measurements were repeated after 10 (SD 4) weeks of galantamine. Baseline cerebrovascular resistance was higher in AD (AD 2.83 (0.87) mmHg/cm/s, control 2.24 (1.3) mmHg/cm/s, p=0.010). 13 AD patients and 17 controls had a sufficiently large postural drop in BP (> 10 mmHg). AD patients had a larger postural decline in the frontal cortical concentration of total hemoglobin (Delta [tHb] AD=1.03 (0.70) micromol/l, control =0.30 (0.90) micromol/l, p=0.015). Moreover, the reduction in oxygenated hemoglobin was 57% larger in AD (p=0.085). Unexpectedly, the postural changes in BP were smaller in AD. Galantamine treatment affected neither orthostatic BP nor the decrease in [tHb]. In conclusion, even for moderate orthostatic hypotension during commonly occurring postural changes, cerebral cortical tissue perfusion declined more in AD, suggesting increased ischemic vulnerability of the brain. Galantamine neither improved nor impaired cerebrovascular regulation.

Amyloid beta protein and tau in cerebrospinal fluid and plasma as biomarkers for dementia: a review of recent literature.

This review addresses recent developments in amyloid beta (Abeta), total tau (t-tau), and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the protection of patients with mild cognitive impairment (MCI) into dementia and the differential diagnosis of Alzheimer's Disease (AD). A combination of Abeta42 and t-tau in CSF can discriminate between patients with stable MCI and patients with progressive MCI into AD or other types of dementia with a sufficient sensitivity and specificity. Regression analyses demonstrated that pathological CSF (with decreased Abeta42 and and increased tau levels) is a very strong predictor for the progression of MCI into AD. Furthermore, CSF measurements of p-tau and Abeta42 can assist in diagnosing vascular dementia or frontotemporal dementia in the differential diagnosis of AD indicated by a reasonable sensitivity and specificity. Whether tau in combination with Abeta42 or in combination with the Abeta37/Abeta42 or Abeta38/Abeta42 ratio aids in the discrimination between AD and Lewy Body dementia remains to be elucidated. Cross-sectional research could not demonstrate significant differences for Abeta40 and Abeta42 in plasma between AD and controls. However, a recently published longitudinal study showed high baseline Abeta40 levels, especially when combined with low baseline Abeta 42 levels, are a strong risk factor for the development of dementia. This emphasizes the importance of performing longitudinal studies in addition to cross-sectional ones. The origin of plasma Abeta and its transport between CSF and plasma, however, needs further clarification. In conclusion, progress has been made regarding Abeta and tau as biomarkers for dementia, both for differentiation between stable MCI and progressive MCI patients and for the differential diagnosis of AD. Future research should aim to validate these recently published results, preferably in pathologically confirmed AD patients. In addition, it is important to standardise research in terms of study design (longitudinal, minimal follow-up period of 5 years), type of researched parameters ( total or p-tau, type of Abeta peptides), type of matrix (CSF and plasma) and data analysis (establishment of predefined cut-off values, type of ratio, type of marker combination).

Non-cardiovascular co-morbidity in elderly patients with heart failure outnumbers cardiovascular co-morbidity.

BACKGROUND: Patients with heart failure often suffer from multiple co-morbid conditions. However, until now only cardiovascular co-morbidity has been well described. AIMS: To understand heart failure in the context of multi-morbidity, by describing the age and sex specific patterns of non-cardiovascular co-morbidity in elderly patients with heart failure in general practice. METHODS: All patients aged 65 years and over, diagnosed with heart failure in four practices of the Nijmegen Academic Practice-based Research Network (NPBRN) between January 1999 and December 2003 were selected, and the prevalence of 27 cardio- and non-cardiovascular co-morbidities determined. RESULTS: Of the 269 patients identified (mean age 79 years; 57% women), 80.2% had four or more co-morbidities. With increasing age, a significant increase in the prevalence of non-cardiovascular conditions like visual and hearing impairments, osteoarthritis, dementia and urine incontinence; and a decrease in cardiovascular conditions like myocardial infarction and in women, hypertension, was observed. In patients aged 85 years and over, non-cardiovascular disorders predominated over cardiovascular disorders. CONCLUSIONS: In elderly patients with heart failure, the prevalence of non-cardiovascular co-morbidity is very high and exceeds the prevalence of cardiovascular conditions. Diseases such as dementia and osteoarthritis must be taken into account in the management of elderly patients with heart failure.

Cerebrospinal fluid amyloid beta42/phosphorylated tau ratio discriminates between Alzheimer's disease and vascular dementia.

BACKGROUND: The differentiation of Alzheimer's disease (AD) from vascular dementia (VaD) is hampered by clinical diagnostic criteria with disappointing sensitivity and specificity. The objective of this study was to investigate whether cerebrospinal fluid (CSF) levels of total tau protein (t-tau), amyloid beta42 protein (Abeta42), and tau phosphorylated at threonine 181 (p-tau181) are useful biomarkers to distinguish AD patients from VaD patients. METHODS: We measured CSF levels of p-tau181, Abeta42, and t-tau in 86 patients with a clinical diagnosis of AD or VaD and in 30 control participants. RESULTS: Optimal differentiation between AD and VaD was achieved by using the ratio of the CSF levels of Abeta42 and p-tau181 (Q Abeta42/p-tau) with sensitivity, specificity, positive and negative predictive values all > or = 85%. CONCLUSIONS: Our results support further efforts to prospectively validate the use of Q Abeta42/p-tau as a biomarker to discriminate between AD and VaD.

Cholinergically mediated augmentation of cerebral perfusion in Alzheimer's disease and related cognitive disorders: the cholinergic-vascular hypothesis.

The treatment of Alzheimer's disease (AD) with cholinesterase inhibitors (ChEIs) is based on the cholinergic hypothesis. This hypothesis fails to account for the global nature of the clinical effects of ChEIs, for the replication of these effects in other dementias, and for the strong and unpredictable intraindividual variation in response to treatment. These findings may be better explained by the premise that ChEIs primarily act by augmenting cerebral perfusion: the cholinergic-vascular hypothesis. This article will review the evidence from preclinical and clinical investigations on the vascular role of the cholinergic neural system. The clinical relevance of this hypothesis is discussed with respect to its interactions with the vascular and amyloid hypotheses of AD. Implications for treatment are indicated. Finally, we propose that the role of the cholinergic system in neurovascular regulation and functional hyperemia elucidates how the cholinergic deficit in AD contributes to the clinical and pathological features of this disease.

Detection of elevated pulmonary capillary wedge pressure in elderly patients with various cardiac disorders by the Valsalva manoeuvre.

In the present study, we assessed whether elevated (> or =15 mmHg) PCWP (pulmonary capillary wedge pressure) can be detected using the blood pressure response to the Valsalva manoeuvre in a group of elderly patients with various cardiac disorders, including atrial fibrillation and valvular heart disease, and healthy elderly controls. The Valsalva manoeuvre was performed in 93 patients (71+/-4 years) and 28 healthy controls (70+/-4 years) undergoing right-sided cardiac catheterization. Blood pressure was measured non-invasively with Finapres. PPR (pulse pressure ratio), the ratio of minimum pulse pressure during phase 2 and maximum pulse pressure during phase 1 of the Valsalva manoeuvre, was correlated with PCWP (r=0.63, P<0.001). The area under the receiver operator characteristic curve of PPR with elevated PCWP was 0.85 (P<0.001). For PPR=0.62, sensitivity for elevated PCWP was 80%, specificity was 79%, positive predictive value was 76% and negative predictive value was 83%. Correlation of PPR with PCWP and the ability of PPR to detect elevated PCWP was present in atrial fibrillation, heart failure and valvular heart disease. In conclusion, PPR is a sensitive and specific instrument to diagnose elevated PCWP non-invasively in a large group of elderly patients with various cardiac disorders. This makes the Valsalva manoeuvre a useful non-invasive tool for diagnosing heart failure, applicable in elderly patients with common cardiac disorders, such as atrial fibrillation and valvular heart disease.