Search

Dilation of perivascular spaces (PVS) in the brain may indicate poor fluid drainage due to the accumulation of perivascular cell debris, waste, and proteins, including amyloid-beta (Aβ). No prior study has assessed whether plasma Aβ levels are related to PVS in older adults without dementia. Independently living older adults (N = 56, mean age = 68.2 years; Standard deviation (SD) = 6.5; 30.4% male) free of dementia or clinical stroke were recruited from the community and underwent brain MRI and venipuncture. PVS were qualitatively scored and dichotomized to low PVS burden (scores 0-1,) or high PVS burden (score>1). Plasma was assayed using a Quanterix Simoa Kit to quantify Aβ42 and Aβ40 levels. A significant difference was observed in plasma Aβ42/Aβ40 ratio between low and high PVS burden, controlling for age (F[1, 53] = 5.59, p = 0.022, η2 = 0.10), with lower Aβ42/Aβ40 ratio in the high PVS burden group. Dilation of PVS is associated with a lower plasma Aβ42/Aβ40 ratio, which may indicate higher cortical amyloid deposition. Future longitudinal studies examining PVS changes, and the pathogenesis of AD are warranted.

BackgroundElevated blood pressure (BP) variability is predictive of increased risk for stroke, cerebrovascular disease, and other vascular brain injuries, independent of traditionally studied average BP levels. However, no studies to date have evaluated whether BP variability is related to diminished cerebrovascular reactivity, which may represent an early marker of cerebrovascular dysfunction presaging vascular brain injury.MethodsThe present study investigated BP variability and cerebrovascular reactivity in a sample of 41 community-dwelling older adults (mean age 69.6 [SD 8.7] years) without a history of dementia or stroke. Short-term BP variability was determined from BP measurements collected continuously during a 5-minute resting period followed by cerebrovascular reactivity during 5-minute hypocapnia and hypercapnia challenge induced by visually guided breathing conditions. Cerebrovascular reactivity was quantified as percent change in cerebral perfusion by pseudo-continuous arterial spin labeling (pCASL)-MRI per unit change in end-tidal CO2.ResultsElevated systolic BP variability was related to lower whole brain cerebrovascular reactivity during hypocapnia (ß = -0.43 [95% CI -0.73, -0.12]; P = 0.008; adjusted R2 =.11) and hypercapnia (ß = -0.42 [95% CI -0.77, -0.06]; P = 0.02; adjusted R2 = 0.19).ConclusionsFindings add to prior work linking BP variability and cerebrovascular disease burden and suggest BP variability may also be related to prodromal markers of cerebrovascular dysfunction and disease, with potential therapeutic implications.

BackgroundPerivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR.MethodsIndependently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales.ResultsThirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55-84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia.DiscussionPerivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

Drawing on case study evidence, this article explores the development of compulsory courses in a China's high-level comprehensive university, which has achieved good results in the procedure of Quality Assessment of Undergraduate Education (QAUE) and China Discipline Ranking (CDR) issued by Ministry of Education (MOE). The general undergraduate majors of this university are classified into 5 categories, namely, journalism and communication, economics and management, science and engineering, foreign language and literature, humanities and social science. The research scope is from grade 2007 to 2017, 2007 fall to 2018 spring semester, respectively. According to the requirements of MOE, the compulsory courses are divided into two parts: public and professional. The public part mainly refers to the courses of physical education, ideological and political and elementary computer science, while the professional part is mostly relevant to the courses associate with the major. The laws of two parts are studied by utilizing the features of course name, course ID, credits and appropriate semester. The conditions of characteristic development, the workload of teachers and students and the interdisciplinary platform, which are universal in Chinese Higher Education Institutions (HEIs), are mentioned.

Blood pressure variability is an emerging risk factor for stroke, cognitive impairment, and dementia, possibly through links with cerebral hypoperfusion. Recent evidence suggests visit-to-visit (e.g., over months, years) blood pressure variability is related to cerebral perfusion decline in brain regions vulnerable to Alzheimer's disease. However, less is known about relationships between short-term (e.g., < 24 hours) blood pressure variability and regional cerebral perfusion, and whether these relationships may differ by age. We investigated short-term blood pressure variability and concurrent regional cerebral microvascular perfusion in a sample of community-dwelling older adults without history of dementia or stroke and healthy younger adults. Blood pressure was collected continuously during perfusion MRI. Cerebral blood flow was determined for several brain regions implicated in cerebrovascular dysfunction in Alzheimer's disease. Elevated systolic blood pressure variability was related to lower levels of concurrent cerebral perfusion in medial temporal regions: hippocampus (β = -.60 [95% CI -.90, -.30]; p < .001), parahippocampal gyrus (β = -.57 [95% CI -.89, -.25]; p = .001), entorhinal cortex (β = -.42 [95% CI -.73, -.12]; p = .009), and perirhinal cortex (β = -.37 [95% CI -.72, -.03]; p = .04), and not in other regions, and in older adults only. Findings suggest a possible age-related selective vulnerability of the medial temporal lobes to hypoperfusion in the context of short-term blood pressure fluctuations, independent of average blood pressure, white matter hyperintensities, and gray matter volume, which may underpin the increased risk for dementia associated with elevated BPV.

Blood pressure variability is an emerging risk factor for Alzheimer's disease in older adults, independent of average blood pressure levels. Growing evidence suggests increased blood pressure variability is linked to Alzheimer's disease pathophysiology indexed by cerebrospinal fluid and positron emission tomography markers, but relationships with plasma Alzheimer's disease markers have not been investigated. In this cross-sectional study of 54 community-dwelling older adults (aged 55-88, mean age 69.9 [8.2 SD]), elevated blood pressure variability over 5 min was associated with lower levels of plasma Aβ1-42 (standardized ß =  - 0.36 [95% CI - 0.61, - 0.12]; p = 0.005; adjusted R2 = 0.28) and Aβ1-42: Aβ1-40 ratio (ß =  - 0.49 [95% CI - 0.71, - 0.22]; p

Neuropathological research suggests the tau pathology of Alzheimer's disease may originate in brainstem nuclei, yet it remains unknown whether tau-mediated degeneration of brainstem nuclei influences cognitive impairment in prodromal Alzheimer's disease. The present study examined cognitive domains impacted in prodromal Alzheimer's disease and brainstem substructure volume in cognitively normal older adults (n = 814) and those with mild cognitive impairment (n = 542). Subsamples of cognitively normal (n = 112) and mild cognitive impairment (n = 202) also had cerebrospinal fluid Alzheimer's disease biomarker characterization. Region-of-interest and voxel-level analyses related whole brainstem, midbrain, pons, and locus coeruleus volumes to cognition with multiple linear regression models corrected for age, sex, education, apolipoprotein-ε4 carrier status, and MRI magnet strength. Within mild cognitive impairment participants, smaller midbrain and locus coeruleus volumes were significantly related to poorer performance on tests of attention and executive function, and the relationship between locus coeruleus volume and executive abilities remained significant in the mild cognitive impairment subsample with biomarker-confirmed Alzheimer's disease. A brainstem-masked voxel-wise regression further demonstrated an association between locus coeruleus volume and executive abilities. Brainstem volumes were not significantly related to memory processes. Study findings implicate midbrain and locus coeruleus volume in attention and executive deficits in mild cognitive impairment. Together with prior neuropathological studies, our data suggest a link between Alzheimer's disease-related degeneration of brainstem nuclei and cognitive deficits in prodromal Alzheimer's disease.

Blood pressure variability (BPV) is linked to dementia risk, possibly through cerebral hypoperfusion. We investigated BPV over 1 year and concurrent regional cerebral perfusion decline in older adults without dementia. Participants underwent 4 blood pressure measurements across 12 months, ASL-MRI at baseline and 12-months, and baseline FDG-PET. Regional perfusion was normalized to precentral gyrus. A subset had cerebral spinal fluid Alzheimer's disease biomarker abnormalities. For every SD increase in BPV, perfusion decreased in medial orbitofrontal cortex (ß = -.36; p = 0.008), hippocampus (ß = -.37; p = 0.005), entorhinal cortex (ß = -.48; p < 0.001), precuneus (ß = -.31; p = 0.02), inferior parietal cortex (ß = -.44; p < 0.001), and inferior temporal cortex (ß = -.46; p < 0.001). Similar patterns emerged in subsets with biomarker abnormalities. Older adults with elevated BPV exhibit concurrent regional perfusion decline in areas vulnerable to Alzheimer's disease, independent of cerebral hypometabolism. BPV may be an early marker of vascular dysfunction in aging.

Loess landslides result in heavy casualties and economic losses. Among them, toppling is one of the predominant failure modes in Malan loess. Loess toppling failure normally arises from deep vertical cracks, which tend to develop in the shoulder areas of loess slopes and extend to a depth of several meters. Under natural conditions, loess' static lateral pressure coefficient is low and the loess mass within a 2 m horizontal depth from the slope surface approximates an unconfined compression stress state. In this work, we sought to further examine this unconfined compression state using acoustic emission monitoring and in situ computed tomography scans to investigate the mechanical behavior of Malan loess. Results indicated that Malan loess failed under compression-induced tension in unconfined compression condition. It exhibited the brittle failure with an abrupt release of elastic energy. The failure plane was at large angles and occurred nearly along the loading axis. This result coincided well with the vertiloess structure, which is characterized by vertically aligned strong units and weak segments. The above failure mode supports the formation of vertical cracks in the loess strata and consequently the toppling and crack sliding slope failures, as well as the formation of loess walls and columns. Key words: Malan loess, unconfined compression, vertiloess structure, surficial strain, acoustic emission, in situ CT, 1. Introduction Loess is a grayish yellow, highly porous, clastic, and brittle aeolian sediment that accounts for approximately 6% of the total global land area (Li et al. 2020a). It [...]

BackgroundNeuropathological studies have suggested the tau pathology observed in Alzheimer's disease (AD) originates in brainstem nuclei, but no studies to date have quantified brainstem volumes in clinical populations with biomarker-confirmed mild cognitive impairment (MCI) or dementia due to AD or determined the value of brainstem volumetrics in predicting dementia.ObjectiveThe present study examined whether MRI-based brainstem volumes differ among cognitively normal older adults and those with MCI or dementia due to AD and whether preclinical brainstem volumes predict future progression to dementia.MethodsAlzheimer's Disease Neuroimaging Initiative participants (N = 1,629) underwent baseline MRI scanning with variable clinical follow-up (6-120 months). Region of interest and voxel-based morphometric methods assessed brainstem volume differences among cognitively normal (n = 814), MCI (n = 542), and AD (n = 273) participants, as well as subsets of cerebrospinal fluid biomarker-confirmed MCI (n = 203) and AD (n = 160) participants.ResultsMCI and AD cases showed smaller midbrain volumes relative to cognitively normal participants when normalizing to whole brainstem volume, and showed smaller midbrain, locus coeruleus, pons, and whole brainstem volumes when normalizing to total intracranial volume. Cognitively normal individuals who later progressed to AD dementia diagnosis exhibited smaller baseline midbrain volumes than individuals who did not develop dementia, and voxel-wise analyses revealed specific volumetric reduction of the locus coeruleus.ConclusionFindings are consistent with neuropathological observations of early AD-related pathology in brainstem nuclei and further suggest the clinical relevance of brainstem substructural volumes in preclinical and prodromal AD.