Neuropsychiatric Correlates of Small Vessel Disease Progression in Incident Cognitive Decline: Independent and Interactive Effects

BACKGROUND: Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited. OBJECTIVE: This study investigated the role of SVD and NPS progressions on cognitive outcomes over 2 years in a dementia-free elderly cohort. METHODS: 170 dementia-free elderly with baseline and 2-year neuropsychological assessments and MRI scans were included in this study. White matter hyperintensities (WMH), lacunes, and microbleeds (CMBs) were graded as markers of SVD. The Ne

Interactions of comorbid neuropsychiatric subsyndromes with neurodegenerative and cerebrovascular pathologies on cognition

Comorbid neuropsychiatric symptoms are commonly found in individuals with dementia and is likely influenced by a combination of neurodegenerative and cerebrovascular pathophysiology. We evaluated the associations of a validated composite MRI-based quantitative measure of both neurodegeneration (hippocampus volume and cortical thickness of AD-specific regions) and cerebrovascular disease (CeVD; white matter hyperintensities and infarcts) with neuropsychiatric subsyndromes, and their interactions on cognition in a community-based sample across the disease spectrum (N = 773). Lower composite MRI scores corresponding to greater comorbid neurodegeneration and CeVD burden were associated with hyperactivity (OR = 1.48) and apathy (OR = 1.90) subsyndromes. Lower MRI scores with concomitant hyperactivity was associated with greater cognitive impairment, especially in patients who were at least moderately impaired, while the interaction with apathy was not dependent on disease stage. These MRI scores interaction models resulted in a better fit than models consisting of neurodegeneration or CeVD alone. Integrating multiple biomarkers with specific, disease stage-dependent neuropsychiatric subsyndromes may provide a more holistic risk profile to facilitate the identification of individuals at the highest risk of disease progression.Ministry of Education (MOE)Nanyang Technological UniversityNational Medical Research Council (NMRC)Submitted/Accepted versionThis study was supported by Nanyang Technological University, Singapore Start-Up Grant M40824100 and MOE AcRF Tier 1 M4012193. The Epidemiology of Dementia in Singapore (EDIS) study is supported by the National Medical Research Council (NMRC), Singapore (NMRC/CG/NUHS/2010 [Grant no.: R-184-006- 184-511]) and (NMRC/CSA/038/2013)

Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics

10.3390/antiox11091717ANTIOXIDANTS11

Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics

Low blood concentrations of the diet-derived compound ergothioneine (ET) have been associated with cognitive impairment and cerebrovascular disease (CeVD) in cross-sectional studies, but it is unclear whether ET levels can predict subsequent cognitive and functional decline. Here, we examined the temporal relationships between plasma ET status and cognition in a cohort of 470 elderly subjects attending memory clinics in Singapore. All participants underwent baseline plasma ET measurements as well as neuroimaging for CeVD and brain atrophy. Neuropsychological tests of cognition and function were assessed at baseline and follow-up visits for up to five years. Lower plasma ET levels were associated with poorer baseline cognitive performance and faster rates of decline in function as well as in multiple cognitive domains including memory, executive function, attention, visuomotor speed, and language. In subgroup analyses, the longitudinal associations were found only in non-demented individuals. Mediation analyses showed that the effects of ET on cognition seemed to be largely explainable by severity of concomitant CeVD, specifically white matter hyperintensities, and brain atrophy. Our findings support further assessment of plasma ET as a prognostic biomarker for accelerated cognitive and functional decline in pre-dementia and suggest possible therapeutic and preventative measures

Supplemental Material, Supplementary_Table_1 - Caregiver-Reported Sleep Disturbances Are Associated With Behavioral and Psychological Symptoms in an Asian Elderly Cohort With Cognitive Impairment-No Dementia

<p>Supplemental Material, Supplementary_Table_1 for Caregiver-Reported Sleep Disturbances Are Associated With Behavioral and Psychological Symptoms in an Asian Elderly Cohort With Cognitive Impairment-No Dementia by Xin Xu, Cheuk Ni Kan, Tien Yin Wong, Ching-Yu Cheng, M. Kamran Ikram, Christopher Li-Hsian Chen, and Narayanaswamy Venketasubramanian in Journal of Geriatric Psychiatry and Neurology</p

White matter hyperintensity volume and post-stroke cognition: an individual patient data pooled analysis of nine ischemic stroke cohort studies

Background and aims: White matter hyperintensities (WMH) are associated with cognitive dysfunction after ischemic stroke. Yet uncertainty remains about affected domains, the role of other pre-existing brain injury, and infarct-types in the relation between WMH burden and post-stroke cognition. We aimed to disentangle these factors in a large sample of patients with ischemic stroke from different cohorts. Methods We pooled and harmonized individual patient data (n=1568) from 9 cohorts, through the Meta VCI Map consortium (www.metavcimap.org). Included cohorts comprised patients with available MRI and multi-domain cognitive assessment &lt;15 months post73 stroke. Linear mixed models were used to determine the association between WMH volume and domain-specific cognitive functioning (z-scores; attention &amp; executive functioning, processing speed, language and verbal memory) for the total sample and stratified by infarct-type. Pre-existing brain injury was accounted for in the multivariable models and all analyses were corrected for study site as a random effect.. Results In the total sample (67 years (SD 11.5), 40% female), we found a dose-dependent inverse relationship between WMH volume and post-stroke cognitive functioning across all four cognitive domains (coefficients ranging from -0.09 (SE 0.04, p=0.01) for verbal memory to -0.19 (SE 0.03, p&lt;0.001) for attention &amp; executive functioning). This relation was independent of acute infarct volume and presence of lacunes and old infarcts. In stratified analyses, the relation between WMH volume and domain86 specific functioning was also largely independent of infarct-type. Conclusion: In patients with ischemic stroke, increasing WMH volume is independently associated with worse cognitive functioning across all major domains, regardless of old ischemic lesions and infarct-type

Intracellular Trafficking of Polyamidoamine–Poly(ethylene glycol) Block Copolymers in DNA Delivery

available in PMC 2012 August 17The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we developed a modular, linear–dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility and protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high-throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system.National Institutes of Health (U.S.) (NIBIB Grant R01EB008082)United States. Dept. of Defense (National Defense Science and Engineering Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship Program)MIT-Harvard Center for Cancer Nanotechnology Excellence (NCI grant 1U54CA151884