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 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.

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%.

Maximized song learning of juvenile male zebra finches following BDNF expression in the HVC.

During song learning, vocal patterns are matched to an auditory memory acquired from a tutor, a process involving sensorimotor feedback. Song sensorimotor learning and song production of birds is controlled by a set of interconnected brain nuclei, the song control system. In male zebra finches, the beginning of the sensorimotor phase of song learning parallels an increase of the brain-derived neurotrophic factor (BDNF) in just one part of the song control system, the forebrain nucleus HVC. We report here that transient BDNF-mRNA upregulation in the HVC results in a maximized copying of song syllables. Each treated bird shows motor learning to an extent similar to that of the selected best learners among untreated zebra finches. Because this result was not found following BDNF overexpression in the target areas of HVC within the song system, HVC-anchored mechanisms are limiting sensorimotor vocal learning.

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.

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.

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.

Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries.

Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC.

Opportunistic screening for atrial fibrillation with a single lead device in geriatric patients.

OBJECTIVE: To determine the diagnostic yield of repeated screening for atrial fibrillation (AF) among geriatric patients. METHODS: A pragmatic prospective cohort study into applying opportunistic screening for AF with a handheld single lead ECG device (SLD) in a geriatric cohort. Consecutive patients of 65 years old and older visiting the geriatric outpatient clinic were eligible for inclusion. A 12 lead ECG was performed, followed by measurements with the SLD during every visit to the geriatric outpatient clinic. A frailty index was based on the accumulation of deficits model. RESULTS: 478 patients were eligible. Patients were excluded if they did not give informed consent (17 patients), had a pacemaker or implantable cardioverter defibrillator (20 patients), or had incomplete medical files (two patients). After exclusion, 439 patients participated in this study. The mean age was 78 years (range 65 to 100 years), 54% were female. AF was known in 89 patients (20%), first detected on the baseline ECG in four patients (1%) and first detected with the SLD in 20 patients (5%) during follow up visits. Sensitivity of the SLD was 90.0%, specificity 99.0%, negative predictive value 99.7%, and positive predictive value 73.5%. Most patients (82%) with AF were frail and 53% were severely frail. CONCLUSION: Repeated screening in geriatric patients has a five times higher diagnostic yield than usual care. It was easily combined with usual care. Because of the positive predictive value of 73.5%, it remains necessary to confirm AF with a 12 lead ECG or 24-h Holter monitoring.

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.

Assessing aversive emotional states through the heart in mice: implications for cardiovascular dysregulation in affective disorders.

Beat-to-beat fluctuations of heart rate (HR) convey information of the brain state with the cardiac time series reflecting the flow of efferent nerve traffic of the autonomic nervous system. Instantaneous HR was studied in mice during exposure to novelty and the expression of fear conditioned to an auditory cue as affective challenge to characterize baseline dynamics and conditioned adjustments to learned fear. These studies included pharmacological and genetic interventions of brain systems implicated in aversive emotional states, the corticotropin-releasing factor (CRF) system and the serotonin (5-HT)1A receptor. Non-linear analyses of neuroautonomic cardiac control provide for functionally adequate measures of dynamical properties. Both CRF1 and 5-HT1A receptor agonists elicited profound sympatho-vagal antagonism with pathological HR dynamics indicative of central autonomic dysregulation via mechanisms resulting in impaired fear adjustment. Non-linear measures provide for a qualitative assessment of dynamical features with regard to physiological or pathological state, are crucial for the translation of results from mouse to man, and may improve our understanding of brain-heart interactions for autonomic dysregulation in affective disorders.

Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly.

Cerebral autoregulation (CA) refers to the properties of the brain vascular bed to maintain cerebral perfusion despite changes in blood pressure (BP). Whereas classic studies have assessed CA during changes in BP that have a gradual onset, dynamic studies quantify the fast modifications in cerebral blood flow (CBF) in relation to rapid alterations in BP. There is a lack of standardization in the assessment of dynamic CA. This review provides an overview of the methods that have been applied, with special focus on the elderly. We will discuss the relative merits and shortcomings of these methods with regard to the aged population. Furthermore, we summarize the effects of variability in BP on CBF in older people. Of the various dynamic assessments of CA, a single sit-to-stand procedure is a feasible and physiologic method in the elderly. The collection of spontaneous beat-to-beat changes in BP and CBF allows estimation of CA using the technique of transfer function analysis. A thorough search of the literature yielded eight studies that have measured dynamic CA in the elderly aged <75 years. Regardless of the methods used, it was concluded from these studies that CA was preserved in this population.

Differential involvement of the dorsal hippocampus in passive avoidance in C57bl/6J and DBA/2J mice.

The inferior performance of DBA/2 mice when compared to C57BL/6 mice in hippocampus-dependent behavioral tasks including contextual fear conditioning has been attributed to impaired hippocampal function. However, DBA/2J mice have been reported to perform similarly or even better than C57BL/6J mice in the passive avoidance (PA) task that most likely also depends on hippocampal function. The apparent discrepancy in PA versus fear conditioning performance in these two strains of mice was investigated using an automated PA system. The aim was to determine whether these two mouse strains utilize different strategies involving a different contribution of hippocampal mechanisms to encode PA. C57BL/6J mice exhibited significantly longer retention latencies than DBA/2J mice when tested 24 h after training irrespective of the circadian cycle. Dorsohippocampal NMDA receptor inhibition by local injection of the selective antagonist DL-2-amino-5-phosphonovaleric acid (AP5, 3.2 microg/mouse) before training resulted in impaired PA retention in C57BL/6J but not in DBA/2J mice. Furthermore, nonreinforced pre-exposure to the PA system before training caused a latent inhibition-like reduction of retention latencies in C57BL/6J, whereas it improved PA retention in DBA/2J mice. These pre-exposure experiments facilitated the discrimination of hippocampal involvement without local pharmacological intervention. The results indicate differences in PA learning between these two strains based on a different NMDA receptor involvement in the dorsal hippocampus in this emotional learning task. We hypothesize that mouse strains can differ in their PA learning performance based on their relative ability to form associations on the basis of unisensory versus multisensory contextual/spatial cues that involve hippocampal processing.

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.

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.

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.

Melatonin affects the temporal organization of the song of the zebra finch.

In birds and mammals, including humans, melatonin-binding sites are abundant in brain areas that have no known clock function. Although the role of such binding sites is still unclear, it is assumed that these sites link neural functions to circadian or circannual demands of neuroendocrine homeostasis and reproduction. To investigate a possible direct role of melatonin in motor control, we studied the song and neural song system of the zebra finch. Neurons of two sensory-motor areas of the descending song control circuit that are crucial for the organization of the song pattern, the HVC and RA, express the melatonin-1B receptor (Mel1B), while the hypoglossal motor neurons of the song circuit express melatonin-1C receptors (Mel1C). Application of melatonin to brain slices decreases the firing-rate of RA-neurons. Systemic administration of a Mel1B antagonist at the beginning of the night shortens the song and motif length and affects the song syllable lengths produced the next day. The temporal pattern of the song, however, does not undergo daily changes. Thus, melatonin is likely to affect a non-circadian motor pattern by local modulation of song control neurons and in consequence alters a sexual signal, the song of the zebra finch.

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.

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.