Temporal dynamics of depressive symptoms and cognitive decline in the oldest old: dynamic time warp analysis of the Leiden 85-plus study.

Background: The prevalence of depressive symptoms and cognitive decline increases with age. We investigated their temporal dynamics in individuals aged 85 and older across a 5-year follow-up period.

Methods: Participants were selected from the Leiden 85-plus study and were eligible if at least three follow-up measurements were available (325 of 599 participants).

Distinct functional subnetworks of cognitive domains in older adults with minor cognitive deficits.

Although past research has established a relationship between functional connectivity and cognitive function, less is known about which cognitive domains are associated with which specific functional networks. This study investigated associations between functional connectivity and global cognitive function and performance in the domains of memory, executive function and psychomotor speed in 166 older adults aged 75-91 years (mean = 80.3 ± 3.

Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies.

Monoclonal antibodies have become an important class of therapeutics in the last 30 years. Because the mechanism of action of therapeutic antibodies is intimately linked to their binding epitopes, identification of the epitope of an antibody to the antigen plays a central role during antibody drug development. The gold standard of epitope mapping, X-ray crystallography, requires a high degree of proficiency with no guarantee of success.

Functional connectivity in older adults-the effect of cerebral small vessel disease.

Ageing is associated with functional reorganization that is mainly characterized by declining functional connectivity due to general neurodegeneration and increasing incidence of disease. Functional connectivity has been studied across the lifespan; however, there is a paucity of research within the older groups (≥75 years) where neurodegeneration and disease prevalence are at its highest. In this cross-sectional study, we investigated associations between age and functional connectivity and the influence of cerebral small vessel disease (CSVD)-a common age-related morbidity-in 167 community-dwelling older adults aged 75-91 years (mean = 80.

Preclinical characterization and clinical translation of pharmacodynamic markers for MK-5890: a human CD27 activating antibody for cancer immunotherapy.

Background: Immune checkpoint inhibitors (ICI) have radically changed cancer therapy, but most patients with cancer are unresponsive or relapse after treatment. MK-5890 is a CD27 agonist antibody intended to complement ICI therapy. CD27 is a member of the tumor necrosis factor receptor superfamily that plays a critical role in promoting responses of T cells, B cells and NK cells.

Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning.

The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e.

Lower Blood Pressure, Small-Vessel Disease, and Apathy in Older Persons With Mild Cognitive Deficits.

Background: In older persons, both high and low blood pressure (BP) levels are associated with symptoms of apathy. Population characteristics, such as burden of cerebral small-vessel disease (CSVD), may underlie these apparently contradictory findings. We aimed to explore, in older persons, whether the burden of CSVD affects the association between BP and apathy.

Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.

Frequent Cognitive Impairment in Patients With Disorders Along the Heart-Brain Axis.

Background and Purpose- Patients with cardiovascular disease are at increased risk for cognitive decline. We studied the occurrence and profile of cognitive impairment in 3 patient groups as exemplar conditions of hemodynamic disturbances at different levels of the heart-brain axis, including patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (possible vascular cognitive impairment [VCI]). Methods- In 555 participants (160 HF, 107 COD, 160 possible VCI, 128 reference participants; 68±9 years; 36% F; Mini-Mental State Examination 28±2), we assessed cognitive functioning with a comprehensive test battery.

The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study.

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI.

High Sensitivity Cardiac Troponin T and Cognitive Function in the Oldest Old: The Leiden 85-Plus Study.

Background: Impaired cardiac function has been related to accelerated cognitive decline in late-life.

Objective: To investigate whether higher levels of high sensitivity cardiac troponin T (hs-cTnT), a sensitive marker for myocardial injury, are associated with worse cognitive function in the oldest old.

Methods: In 455 participants of the population-based Leiden 85-plus Study, hs-cTnT was measured at 86 years.

Hemodynamic and serum cardiac markers and risk of cognitive impairment and dementia.

Introduction: Cardiac function is a key player in maintaining energy homeostasis in the brain. Heart failure is closely related to higher risk of neurocognitive disorders. Recent evidence shows that this relationship might not be limited to patients with advanced heart failure, and even suboptimal cardiac functioning is associated with accelerated brain aging.

Validity of the three apathy items of the Geriatric Depression Scale (GDS-3A) in measuring apathy in older persons.

Objective: The Geriatric Depression Scale (GDS)-3A, a three-item subset of the GDS-15, is increasingly used as a measure for apathy in research settings to assess factors associating with this neuropsychiatric syndrome. We aimed to assess how accurately the GDS-3A discriminates between presence and absence of apathy in two populations of community-dwelling older persons, using the Apathy Scale as reference standard.

Methods: Baseline data were used from 427 participants of the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden and 1118 participants of the PROactive Management Of Depression in the Elderly (PROMODE) Study, all ≥75 years and with available GDS-3A and Apathy Scale measurements.

Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning--the DANTE Study Leiden: A Randomized Clinical Trial.

Importance: Observational studies indicate that lower blood pressure (BP) increases risk for cognitive decline in elderly individuals. Older persons are at risk for impaired cerebral autoregulation; lowering their BP may compromise cerebral blood flow and cognitive function.

Objective: To assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive deficits improves cognitive, psychological, and general daily functioning.

Lower blood pressure and apathy coincide in older persons with poorer functional ability: the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden.

Objectives: To examine the association between blood pressure (BP) measures and symptoms of apathy and depression in older adults with various levels of functional ability.

Design: Cross-sectional study using baseline data from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden.

Setting: Primary care setting, the Netherlands.

Associated autoimmune diseases in patients with multifocal motor neuropathy and their family members.

Multifocal motor neuropathy (MMN) is a rare immune-mediated disorder and is characterized by male predominance, the presence of serum anti-GM1 IgM antibodies in up to half of all patients, responsiveness to intravenous immunoglobulins (IVIg) and an increased frequency of HLA type HLA-DRB1*15. The aim of this study was to assess whether the frequency of autoimmune diseases (AID) is increased in patients with MMN and their first-degree family members, since this would indicate that MMN shares pathogenic mechanisms with other AID. We conducted a case-control study using questionnaires to evaluate the prevalence of AID in MMN and controls, and their first-degree relatives.

SFTG international collaborative study on in vitro micronucleus test II. Using human lymphocytes.

This study on the in vitro micronucleus assay, comprising 11 laboratories using human lymphocytes, was coordinated by an organizing committee supported by the SFTG (the French branch of the European Environmental Mutagen Society). Nine coded substances were assessed for their ability to induce micronuclei in human lymphocytes in vitro, mitomycin C being used as a positive control. Cultures were exposed to the test substances for a short (early or late) time or for a long time, followed by a short or long recovery period, in the presence of cytochalasin B.

Safety evaluation of a lactase enzyme preparation derived from Kluyveromyces lactis.

Neutralact(R), the DSM brand name of a lactase enzyme preparation, obtained from a homologous rDNA strain of Kluyveromyces lactis, was subjected to a series of toxicological tests to document the safety for use as a processing aid in the dairy industry. The enzyme preparation was examined for subacute oral toxicity and mutagenic potential. As a result of these tests, no evidence of oral toxicity, mutagenicity or clastogenicity was found.

On the use of T61 for euthanasia of domestic and laboratory animals; an ethical evaluation.

A number of experiments was carried out to determine the sequence of events leading to death following administration of the euthanizing agent T61. Simultaneous recordings of the EMG, EEG, ECG and end-tidal CO2 (dogs only) were obtained in acutely instrumented rabbits and dogs. Results show that following T61 administration the loss of consciousness and loss of muscle activity occurred simultaneously.

[The use of T61 for the humane killing of pets and laboratory animals].

Experiments were carried out to determine the onset of loss of consciousness and muscle relaxation following administration of the euthanising agent T61. Simultaneous recordings of EMG, EEG, ECG and capnogram (dogs only) were obtained in acutely instrumented rabbits and dogs. The results showed that loss of consciousness and muscle activity occurred simultaneously following administration of T61.

Identification and clinical examination of jaundiced rats.

Rats with or without spontaneously occurring jaundice were clinically examined. Jaundiced rats had five-fold higher serum bilirubin concentrations than control animals. About 90% of serum bilirubin in the jaundiced animals was in conjugated form.

Assessment of discomfort in rats with hepatomegaly.

An attempt was made to assess discomfort in rats with hepatomegaly induced by feeding a high cholesterol, high cholate diet. After 8 weeks, the rats displayed a more than two-fold increase in liver weight when compared with controls fed a commercial diet. In a small open field test, behaviour of rats with hepatomegaly was similar to the controls.