Avian top predator and the landscape of fear: responses of mammalian mesopredators to risk imposed by the golden eagle

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Cerebral Hypoxia and Ischemia in the Pathogenesis of Dementia after Stroke

While it has been reported that ischemic stroke significantly increases the risk of delayed dementia,1,2 the underlying mechanisms are not well understood. Hypoxic and ischemic (HI) injury resulting from cerebral hypoperfusion due to systemic illness has been proposed as a pathogenic mechanism in certain subgroups of patients.1,3 Thus, the aim of this study was to investigate whether cerebral HI injury resulting from certain systemic illnesses (e.g., cardiac arrhythmias, cardiac failure, pneumonia, seizures, sepsis) would be an independent risk factor for the development of incident dementia after ischemic stroke

Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium

Background: Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. Methods: Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. Results: In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. Conclusions: A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology

Insulin Resistance Predicts Cognitive Decline: An 11-Year Follow-up of a Nationally Representative Adult Population Sample

OBJECTIVEThe aim of this study was to examine whether insulin resistance, assessed by HOMA of insulin resistance (HOMA-IR), is an independent predictor of cognitive decline.RESEARCH DESIGN AND METHODSThe roles of HOMA-IR, fasting insulin and glucose, HbA(1c), and hs-CRP as predictors of cognitive performance and its change were evaluated in the Finnish nationwide, population-based Health 2000 Health Examination Survey and its 11-year follow-up, the Health 2011 study (n = 3,695, mean age at baseline 49.3 years, 55.5% women). Categorical verbal fluency, word-list learning, and word-list delayed recall were used as measures of cognitive function. Multivariate linear regression analysis was performed and adjusted for previously reported risk factors for cognitive decline.RESULTSHigher baseline HOMA-IR and fasting insulin levels were independent predictors of poorer verbal fluency performance (P = 0.0002 for both) and of a greater decline in verbal fluency during the follow-up time (P = 0.004 for both). Baseline HOMA-IR and insulin did not predict word-list learning or word-list delayed recall scores. There were no interactions between HOMA-IR and apolipoprotein E epsilon 4 (APOE epsilon 4) genotype, hs-CRP, or type 2 diabetes on the cognitive tests. Fasting glucose and hs-CRP levels at baseline were not associated with cognitive functioning.CONCLUSIONSOur results show that higher serum fasting insulin and insulin resistance predict poorer verbal fluency and a steeper decline in verbal fluency during 11 years in a representative sample of an adult population. Prevention and treatment of insulin resistance might help reduce cognitive decline later in life

Genome-wide association study of antisocial personality disorder

The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N = 370, N = 5850 for controls, GWAS; N = 173, N = 3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR) = 2.19 (1.53-3.14), P = 1.9 x 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR = 1.59 (1.37-1.85), P = 1.6 x 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (beta = 0.68, P = 0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.Peer reviewe

Support groups for dementia caregivers - Predictors for utilisation and expected quality from a family caregiver's point of view: A questionnaire survey PART I*

<p>Abstract</p> <p>Background</p> <p>Support groups have proved to be effective in reducing the burden on family caregivers of dementia patients. Nevertheless, little is known about the factors that influence utilisation or quality expectations of family caregivers. These questions are addressed in the following paper.</p> <p>Methods</p> <p>The cross-sectional study was carried out as an anonymous written survey of family caregivers of dementia patients in Germany. Qualitative and quantitative data from 404 caregivers were analysed using content analysis and binary logistic regression analysis.</p> <p>Results</p> <p>The only significant predictor for utilisation is assessing how helpful support groups are for the individual care situation. Family caregivers all agree that psycho-educative orientation is a priority requirement.</p> <p>Conclusions</p> <p>In order to increase the rate of utilisation, family caregivers must be convinced of the relevant advantages of using support groups. Support groups which offer an exchange of experiences, open discussion, information and advice meet the requirements of family caregivers.</p

Number of teeth and myocardial infarction and stroke among elderly never smokers

<p>Abstract</p> <p>Background</p> <p>In most previous studies the association between number of teeth and cardiovascular diseases has been found to be stronger among younger age groups than in older age groups, which indicates that age may modify the association between number of teeth and cardiovascular diseases.</p> <p>We investigated the association between tooth loss and atherosclerotic vascular diseases such as myocardial infarction and stroke in a homogeneous elderly population.</p> <p>The study population was comprised of a subpopulation of 392 community-living elderly people who participated in the population-based Kuopio 75+ study. The data were collected through an interview, a structured clinical health examination and from patient records. The main outcome measures were a history of diagnosed myocardial infarction and diagnosed ischemic stroke. Prevalence proportion ratios (PPR) were estimated using generalised linear models.</p> <p>Results</p> <p>Edentate subjects had a weakly, statistically non-significantly increased likelihood of a history of myocardial infarction and ischemic stroke compared with dentate subjects. Those with a large number of teeth had a slightly, but not statistically significantly increased likelihood of a history of myocardial infarction and ischemic stroke compared with those with a small number of teeth.</p> <p>Conclusion</p> <p>These data did not show evidence that total or partial tooth loss would be associated with atherosclerotic vascular diseases such as myocardial infarction and ischemic stroke among an elderly population aged 75 years or older.</p

Dementia as a determinant of social and health service use in the last two years of life 1996-2003

<p>Abstract</p> <p>Background</p> <p>Dementia is one of the most common causes of death among old people in Finland and other countries with high life expectancies. Dementing illnesses are the most important disease group behind the need for long-term care and therefore place a considerable burden on the health and social care system. The aim of this study was to assess the effects of dementia and year of death (1998-2003) on health and social service use in the last two years of life among old people.</p> <p>Methods</p> <p>The data were derived from multiple national registers in Finland and comprise all those who died in 1998, 2002 or 2003 and 40% of those who died in 1999-2001 at the age of 70 or over (n = 145 944). We studied the use of hospitals, long-term care and home care in the last two years of life. Statistics were performed using binary logistic regression analyses and negative binomial regression analyses, adjusting for age, gender and comorbidity.</p> <p>Results</p> <p>The proportion of study participants with a dementia diagnosis was 23.5%. People with dementia diagnosis used long-term care more often (OR 9.30, 95% CI 8.60, 10.06) but hospital (OR 0.33, 95% CI 0.31, 0.35) and home care (OR 0.50, 95% CI 0.46, 0.54) less often than people without dementia. The likelihood of using university hospital and long-term care increased during the eight-year study period, while the number of days spent in university and general hospital among the users decreased. Differences in service use between people with and without dementia decreased during the study period.</p> <p>Conclusions</p> <p>Old people with dementia used long-term care to a much greater extent and hospital and home care to a lesser extent than those without dementia. This difference persisted even when controlling for age, gender and comorbidity. It is important that greater attention is paid to ensuring that old people with dementia have equitable access to care.</p

Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

This is the final version. Available from the publisher via the DOI in this record.UK Biobank Sleep Traits GWAS summary statistics are available at the Sleep Disorder Knowledge Portal (SDKP) website (http://www.sleepdisordergenetics.org). All other data are contained within the article and its supplementary information or available upon request.Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.Medical Research Council (MRC

A systematic review of different models of home and community care services for older persons

<p>Abstract</p> <p>Background</p> <p>Costs and consumer preference have led to a shift from the long-term institutional care of aged older people to home and community based care. The aim of this review is to evaluate the outcomes of case managed, integrated or consumer directed home and community care services for older persons, including those with dementia.</p> <p>Methods</p> <p>A systematic review was conducted of non-medical home and community care services for frail older persons. MEDLINE, PsycINFO, CINAHL, AgeLine, Scopus and PubMed were searched from 1994 to May 2009. Two researchers independently reviewed search results.</p> <p>Results</p> <p>Thirty five papers were included in this review. Evidence from randomized controlled trials showed that case management improves function and appropriate use of medications, increases use of community services and reduces nursing home admission. Evidence, mostly from non-randomized trials, showed that integrated care increases service use; randomized trials reported that integrated care does not improve clinical outcomes. The lowest quality evidence was for consumer directed care which appears to increase satisfaction with care and community service use but has little effect on clinical outcomes. Studies were heterogeneous in methodology and results were not consistent.</p> <p>Conclusions</p> <p>The outcomes of each model of care differ and correspond to the model's focus. Combining key elements of all three models may maximize outcomes.</p