Silent brain infarcts and the risk of dementia and cognitive decline

BACKGROUND: Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS: We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS: During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS: Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions

Homocysteine and brain atrophy on MRI of non-demented elderly

Patients with Alzheimer's disease have higher plasma homocysteine levels than controls, but it is uncertain whether higher plasma homocysteine levels are involved in the early pathogenesis of the disease. Hippocampal, amygdalar and global brain atrophy on brain MRI have been proposed as early markers of Alzheimer's disease. In the Rotterdam Scan Study, a population-based study of age-related brain changes in 1077 non-demented people aged 60-90 years, we investigated the association between plasma homocysteine levels and severity of hippocampal, amygdalar and global brain atrophy on MRI. We used axial T(1)-weighted MRIs to visualize global cortical brain atrophy (measured semi-quantitatively; range 0-15) and a 3D HASTE (half-Fourier acquisition single-shot turbo spin echo) sequence in 511 participants to measure hippocampal and amygdalar volumes. We had non-fasting plasma homocysteine levels in 1031 of the participants and in 505 of the participants with hippocampal and amygdalar volumes. Individuals with higher plasma homocysteine levels had, on average, more cortical atrophy [0.23 units (95% CI 0.07-0.38 units) per standard deviation increase in plasma homocysteine levels] and more hippocampal atrophy [difference in left hippocampal volume -0.05 ml (95% CI -0.09 to -0.01) and in right hippocampal volume -0.03 ml (95% CI -0.07 to 0.01) per standard deviation increase in plasma homocysteine levels]. No association was observed between plasma homocysteine levels and amygdalar atrophy. These results support the hypothesis that higher plasma homocysteine levels are associated with more atrophy of the hippocampus and cortical regions in elderly at risk of Alzheimer's disease

Higher estrogen levels are not associated with larger hippocampi and better memory performance

BACKGROUND: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. OBJECTIVE: To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance. DESIGN AND SETTING: Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia. PARTICIPANTS: Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol. MAIN OUTCOME MEASURE: Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall). RESULTS: Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewe

The HI Tully-Fisher Relation of Early-Type Galaxies

We study the HI K-band Tully-Fisher relation and the baryonic Tully-Fisher relation for a sample of 16 early-type galaxies, taken from the ATLAS3D sample, which all have very regular HI disks extending well beyond the optical body (> 5 R_eff). We use the kinematics of these disks to estimate the circular velocity at large radii for these galaxies. We find that the Tully-Fisher relation for our early-type galaxies is offset by about 0.5-0.7 magnitudes from the relation for spiral galaxies. The residuals with respect to the spiral Tully-Fisher relation correlate with estimates of the stellar mass-to-light ratio, suggesting that the offset between the relations is mainly driven by differences in stellar populations. We also observe a small offset between our Tully-Fisher relation with the relation derived for the ATLAS3D sample based on CO data representing the galaxies' inner regions (< 1 R_eff). This indicates that the circular velocities at large radii are systematically 10% lower than those near 0.5-1 R_eff, in line with recent determinations of the shape of the mass profile of early-type galaxies. The baryonic Tully-Fisher relation of our sample is distinctly tighter than the standard one, in particular when using mass-to-light ratios based on dynamical models of the stellar kinematics. We find that the early-type galaxies fall on the spiral baryonic Tully-Fisher relation if one assumes M/L_K = 0.54 M_sun/L_sun for the stellar populations of the spirals, a value similar to that found by recent studies of the dynamics of spiral galaxies. Such a mass-to-light ratio for spiral galaxies would imply that their disks are 60-70% of maximal. Our analysis increases the range of galaxy morphologies for which the baryonic Tully-Fisher relations holds, strengthening previous claims that it is a more fundamental scaling relation than the classical Tully-Fisher relation.Comment: Accepted for publication in Astronomy & Astrophysic

Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia

BACKGROUND: Consumers of light-to-moderate amounts of alcohol have a lower risk of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular disease may contribute to symptoms of Alzheimer disease, reduction of cerebrovascular disease in consumers of light amounts of alcohol could account for that observation. However, a low concentration of alcohol may also have direct effects on the hippocampus, a brain structure highly affected by Alzheimer disease. OBJECTIVE: We investigated alcohol intake in relation to brain magnetic resonance imaging (MRI) findings of presumed vascular

The Bluedisks project, a study of unusually H I-rich galaxies - I. H I sizes and morphology

<p>We introduce the 'Bluedisk' project, a large programme at the Westerbork Synthesis Radio Telescope that has mapped the H i in a sample of 23 nearby galaxies with unusually high H i mass fractions, along with a similar-sized sample of control galaxies. This paper presents the sample selection, observational set-up, data reduction strategy and a first analysis of the sizes and structural properties of the H i discs. We find that the H i-rich galaxies lie on the same H i mass versus H i size relation as normal spiral galaxies, extending it to total H i masses of 2 x 10(10) M-circle dot and radii R1 of similar to 100 kpc. The H i-rich galaxies have significantly larger values of H i-to-optical size ratio and more clumpy H i discs than those of normal spirals. There is no evidence that the discs of H i-rich galaxies are more disturbed. In fact, the centre of the H i distribution corresponds more closely with the centre of the optical light in the H i-rich galaxies than in the controls. All these results argue against a scenario in which new gas has been brought in by mergers. It is possible that they may be more consistent with cooling from a surrounding quasi-static halo of warm/hot gas.</p>

Effects of the DICE Method to Improve Timely Recognition and Treatment of Neuropsychiatric Symptoms in Early Alzheimer's Disease at the Memory Clinic:The BEAT-IT Study

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented.OBJECTIVE: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic.METHODS: We enrolled sixty community-dwelling people with mild cognitive impairment or AD dementia and NPS across six Dutch memory clinics with their caregivers. The first wave underwent care as usual (n = 36) and the second wave underwent the DICE method (n = 24). Outcomes were quality of life (QoL), caregiver burden, NPS severity, NPS-related distress, competence managing NPS, and psychotropic drug use. Reliable change index was calculated to identify responders to the intervention. A cost-effectiveness analysis was performed and semi-structured interviews with a subsample of the intervention group (n = 12).RESULTS: The DICE method did not improve any outcomes over time compared to care as usual. Half of the participants of the intervention group (52%) were identified as responders and showed more NPS and NPS-related distress at baseline compared to non-responders. Interviews revealed substantial heterogeneity among participants regarding NPS-related distress, caregiver burden, and availability of social support. The intervention did not lead to significant gains in quality-adjusted life years and well-being years nor clear savings in health care and societal costs.CONCLUSION: The DICE method showed no benefits at group-level, but individuals with high levels of NPS and NPS-related distress may benefit from this intervention.</p

Observational Dutch Young Symptomatic StrokE studY (ODYSSEY): Study rationale and protocol of a multicentre prospective cohort study

Background: The proportion of strokes occurring in younger adults has been rising over the past decade. Due to the far longer life expectancy in the young, stroke in this group has an even larger socio-economic impact. However, information on etiology and prognosis remains scarce.Methods/design: ODYSSEY is a multicentre prospective cohort study on the prognosis and risk factors of patients with a first-ever TIA, ischemic stroke or intracerebral hemorrhage aged 18 to 49 years. Our aim is to include 1500 patients. Primary outcome will be all cause mortality and risk of recurrent vascular events. Secondary outcome will be the risk of post-stroke epilepsy and cognitive impairment. Patients will complete structured questionnaires on outcome measures and risk factors. Both well-documented and less well-documented risk factors and potentially acute trigger factors will be investigated. Patients will be followed every 6 months for at least 3 years. In addition, an extensive neuropsychological assessment will be administered both at baseline and 1 year after the stroke/TIA. Furthermore we will include 250 stroke-free controls, who will complete baseline assessment and one neuropsychological assessment.Discussion: ODYSSEY is designed to prospectively determine prognosis after a young stroke and get more insight into etiology of patients with a TIA, ischemic stroke and intracerebral hemorrhage in patients aged 18 to 49 years old in a large sample size

The influence of cerebral small vessel disease on default mode network deactivation in mild cognitive impairment

Introduction Cerebral small vessel disease (CSVD) is thought to contribute to cognitive dysfunction in patients with mild cognitive impairment (MCI). The underlying mechanisms, and more specifically, the effects of CSVD on brain functioning in MCI are incompletely understood. The objective of the present study was to examine the effects of CSVD on brain functioning, activation and deactivation, in patients with MCI using task-related functional MRI (fMRI). Methods We included 16 MCI patients with CSVD, 26 MCI patients without CSVD and 25 controls. All participants underwent a physical and neurological examination, neuropsychological testing, structural MRI, and fMRI during a graded working memory paradigm. Results MCI patients with and without CSVD had a similar neuropsychological profile and task performance during fMRI, but differed with respect to underlying (de)activation patterns. MCI patients with CSVD showed impaired deactivation in the precuneus/posterior cingulate cortex, a region known to be involved in the default mode network. In MCI patients without CSVD, brain activation depended on working memory load, as they showed relative 'hyperactivation' during vigilance, and 'hypoactivation' at a high working memory load condition in working memory related brain regions. Conclusions We present evidence that the potential underlying mechanism of CSVD affecting cognition in MCI is through network interference. The observed differences in brain activation and deactivation between MCI patients with and without CSVD, who had a similar 'clinical phenotype', support the view that, in patients with MCI, different types of pathology can contribute to cognitive impairment through different pathways

Early recognition and treatment of neuropsychiatric symptoms to improve quality of life in early Alzheimer's disease

__Background:__ Neuropsychiatric symptoms (NPS) are very common in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and are associated with various disadvantageous clinical outcomes including a negative impact on quality of life, caregiver burden, and accelerated disease progression. Despite growing evidence of the efficacy of (non)pharmacological interventions to reduce these symptoms, NPS remain underrecognized and undertreated in memory clinics. The BEhavioural symptoms in Alzheimer's disease Towards early Identification and Treatment (BEAT-IT) study is developed to (1) investigate the neurobiological etiology of NPS in AD and (2) study the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) approach to structure and standardize the current care of NPS in AD. By means of the DICE method, we aim to improve the quality of life of AD patients with NPS and their caregivers who visit the memory clinic. This paper describes the protocol for the intervention study that incorporates the latter aim. __Methods:__ We aim to enroll a total of 150 community-dwelling patients with MCI or AD and their caregivers in two waves. First, we will recruit a control group who will receive care as usual. Next, the second wave of participants will undergo the DICE method. This approach consists of the following steps: (1) describe the context in which NPS occur, (2) investigate the possible causes, (3) create and implement a treatment pl