Cerebral Small Vessel Disease in Dementia and Depression: a prospective population-based MRI study

__Abstract__ Cerebral white matter lesions and asymptomatic brain infarcts are common in elderly people. These brain lesions are thought to result from cerebral small vessel disease, and their presence and severity increase with age and the presence of arterial hypertension. There is widespread belief that cerebral small vessel disease plays a role in the aetiology of dementia. Small vessel disease is commonly regarded as the primary pathology in subcortical ischemic vascular dementia, one of the subtypes of vascular dementia. Furthermore, vascular factors, including cerebral small vessel disease, are increasingly recognized to be involved in the aetiology of Alzheimer’s disease.8 However, there is hardly any evidence from prospective population-based studies to support these notions

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

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

Unified description of ballistic and diffusive carrier transport in semiconductor structures

A unified theoretical description of ballistic and diffusive carrier transport in parallel-plane semiconductor structures is developed within the semiclassical model. The approach is based on the introduction of a thermo-ballistic current consisting of carriers which move ballistically in the electric field provided by the band edge potential, and are thermalized at certain randomly distributed equilibration points by coupling to the background of impurity atoms and carriers in equilibrium. The sum of the thermo-ballistic and background currents is conserved, and is identified with the physical current. The current-voltage characteristic for nondegenerate systems and the zero-bias conductance for degenerate systems are expressed in terms of a reduced resistance. For arbitrary mean free path and arbitrary shape of the band edge potential profile, this quantity is determined from the solution of an integral equation, which also provides the quasi-Fermi level and the thermo-ballistic current. To illustrate the formalism, a number of simple examples are considered explicitly. The present work is compared with previous attempts towards a unified description of ballistic and diffusive transport.Comment: 23 pages, 10 figures, REVTEX

Synergistic effects of drought and deforestation on the resilience of the south-eastern Amazon rainforest

The south-eastern Amazon rainforest is subject to ongoing deforestation and is expected to become drier due to climate change. Recent analyses of the distribution of tree cover in the tropics show three modes that have been interpreted as representing alternative stable states: forest, savanna and treeless states. This situation implies that a change in environmental conditions, such as in the climate, could cause critical transitions from a forest towards a savanna ecosystem. Shifts to savanna might also occur if perturbations such as deforestation exceed a critical threshold. Recovering the forest would be difficult as the savanna will be stabilized by a feedback between tree cover and fire. Here we explore how environmental changes and perturbations affect the forest by using a simple model with alternative tree-cover states. We focus on the synergistic effects of precipitation reduction and deforestation on the probability of regime shifts in the south-eastern Amazon rainforest. The analysis indicated that in a large part of the south-eastern Amazon basin rainforest and savanna could be two alternative states, although massive forest dieback caused by mean-precipitation reduction alone is unlikely. However, combinations of deforestation and climate change triggered up to 6.6 times as many local regime shifts than the two did separately, causing large permanent forest losses in the studied region. The results emphasize the importance of reducing deforestation rates in order to prevent a climate-induced dieback of the south-eastern Amazon rainforest

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). Method: MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. Results: We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Conclusions: Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. Key Points: • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI

Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status

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