Cerebral microinfarcts affect brain structural network topology in cognitively impaired patients.

Cerebral microinfarcts (CMIs), a novel cerebrovascular marker, are prevalent in Alzheimer's disease (AD) and associated with cognitive impairment. Nonetheless, the underlying mechanism of how CMIs influence cognition remains uncertain. We hypothesized that cortical-CMIs disrupted structural connectivity in the higher-order cognitive networks, leading to cognitive impairment. We analyzed diffusion-MRI data of 92 AD (26 with cortical-CMIs) and 110 cognitive impairment no dementia patients (CIND, 28 with cortical-CMIs). We compared structural network topology between groups with and without cortical-CMIs in AD/CIND, and tested whether structural connectivity mediated the association between cortical-CMIs and cognition. Cortical-CMIs correlated with impaired structural network topology (i.e. lower efficiency/degree centrality in the executive control/dorsal attention networks in CIND, and lower clustering coefficient in the default mode/dorsal attention networks in AD), which mediated the association of cortical-CMIs with visuoconstruction dysfunction. Our findings provide the first in vivo human evidence that cortical-CMIs impair cognition in elderly via disrupting structural connectivity.

Cortical microinfarcts in memory clinic patients are associated with reduced cerebral perfusion.

Cerebral cortical microinfarcts (CMIs) are small ischemic lesions associated with cognitive impairment and dementia. CMIs are frequently observed in cortical watershed areas suggesting that hypoperfusion contributes to their development. We investigated if presence of CMIs was related to a decrease in cerebral perfusion, globally or specifically in cortex surrounding CMIs. In 181 memory clinic patients (mean age 72 ± 9 years, 51% male), CMI presence was rated on 3-T magnetic resonance imaging (MRI). Cerebral perfusion was assessed from cortical gray matter of the anterior circulation using pseudo-continuous arterial spin labeling parameters cerebral blood flow (CBF) (perfusion in mL blood/100 g tissue/min) and spatial coefficient of variation (CoV) (reflecting arterial transit time (ATT)). Patients with CMIs had a 12% lower CBF (beta = -.20) and 22% higher spatial CoV (beta = .20) (both p < .05) without a specific regional pattern on voxel-based CBF analysis. CBF in a 2 cm region-of-interest around the CMIs did not differ from CBF in a reference zone in the contralateral hemisphere. These findings show that CMIs in memory clinic patients are primarily related to global reductions in cerebral perfusion, thus shedding new light on the etiology of vascular brain injury in dementia.

Inter-hemispheric functional dysconnectivity mediates the association of corpus callosum degeneration with memory impairment in AD and amnestic MCI.

Evidences suggested that both corpus callosum (CC) degeneration and alternations of homotopic inter-hemispheric functional connectivity (FC) are present in Alzheimer's disease (AD). However, the associations between region-specific CC degeneration and homotopic inter-hemispheric FC and their relationships with memory deficits in AD remain uncharacterized. We hypothesized that selective CC degeneration is associated with memory impairment in AD and amnestic mild cognitive impairment (aMCI), which is mediated by homotopic inter-hemispheric functional dysconnectivity. Using structural magnetic resonance imaging (MRI) and task-free functional MRI, we assessed the CC volume and inter-hemispheric FC in 66 healthy controls, 41 aMCI and 41 AD. As expected, AD had CC degeneration and attenuated inter-hemispheric homotopic FC. Nevertheless, aMCI had relatively less severe CC degeneration (mainly in mid-anterior, central, and mid-posterior) and no reduction in inter-hemispheric homotopic FC. The degeneration of each CC sub-region was associated with specific inter-hemispheric homotopic functional disconnections in AD and aMCI. More importantly, impairment of inter-hemispheric homotopic FC partially mediated the association between CC (particularly the central and posterior parts) degeneration and memory deficit. Notably, these results remained after controlling for hippocampal volume. Our findings shed light on how CC degeneration and the related inter-hemispheric FC impact memory impairment in early stage of AD.

Cortical microinfarcts on 3T MRI: Clinical correlates in memory-clinic patients.

INTRODUCTION: This is the first study to assess cerebral microinfarcts (CMIs) on 3 tesla (3T) magnetic resonance imaging (MRI) in a memory clinic population. METHODS: We included 238 consecutive patients (aged 72.5 ± 9.1 years) from a memory clinic in Singapore. All patients underwent extensive neurological and neuropsychological testing and 3T MRI on the same day. Cortical CMI rating criteria were adapted from a previous study on 7T MRI. We analyzed the frequency and association of cortical CMIs with demographic, clinical, cognition, and other MRI findings. RESULTS: Seventy-five patients (32%) had cortical CMIs (median 1, range 1-43). Patients with CMIs showed worse cognitive functioning on MMSE, and in the domains of language and visuoconstruction. The presence of CMIs was related to other markers of small vessel disease, but most strongly larger cortical infarcts. Patients with CMIs were more often diagnosed with vascular dementia. DISCUSSION: Cortical CMIs on 3T MRI are a novel marker of cerebrovascular disease in dementia.

Markers of cardiac dysfunction in cognitive impairment and dementia.

Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD).We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia.A case-control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale.We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64-49.79) and dementia (OR: 16.89; 95%CI: 2.02-142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23-48.58). These associations were independent of other vascular risk factors.In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD.

Trade-offs between effectiveness and efficiency in stroke rehabilitation.

BACKGROUND: Most stroke research has studied rehabilitation effectiveness and rehabilitation efficiency separately and not investigated the potential trade-offs between these two indices of rehabilitation. AIMS: To determine whether there is a trade-off between independent factors of rehabilitation effectiveness and rehabilitation efficiency. METHODS: Using a retrospective cohort study design, we studied all stroke patients (n = 2810) from two sub-acute rehabilitation hospitals from 1996 to 2005, representing 87·5% of national bed-years during the same period. RESULTS: Independent predictors of poorer rehabilitation effectiveness and log rehabilitation efficiency were • older age • race-ethnicity • caregiver availability • ischemic stroke • longer time to admission • dementia • admission Barthel Index score, and • length of stay. Rehabilitation effectiveness was lower in females, and the gender differences were significantly lower in those aged ≤70 years (ß -4·7 (95% confidence interval -7·4 to -2·0)). There were trade-offs between effectiveness and efficiency with respect to admission Barthel Index score and length of stay. An increase of 10 in admission Barthel Index score predicted an increase of 3·6% (95% confidence interval 3·2-4·0) in effectiveness but a decrease of 0·04 (95% confidence interval -0·05 to -0·02) in log efficiency (a reduction of efficiency by 1·0 per 30 days). An increase in log length of stay by 1 (length of stay of 2·7 days) predicted an increase of 8·0% (95% confidence interval 5·7-10·3) in effectiveness but a decrease of 0·82 (95% confidence interval -0·90 to -0·74) in log efficiency (equivalent to a reduction in efficiency by 2·3 per 30 days). For optimal rehabilitation effectiveness and rehabilitation efficiency, the admission Barthel Index score was 30-62 and length of stay was 37-41 days. CONCLUSIONS: There are trade-offs between effectiveness and efficiency during inpatient sub-acute stroke rehabilitation with respect to admission functional status and length of stay.