Dataset Information

Cystatin C, cognition, and brain MRI findings in 90+-year-olds.

ABSTRACT: Chronic kidney disease is emerging as a novel risk factor for cerebrovascular disease, but this association remains largely unexplored in older adults. Cystatin C is a more accurate measure than creatinine of kidney function in the elderly. We evaluated cystatin C, cognitive function, and brain imaging in 193 participants from The 90+ Study neuroimaging component. The mean age was 93.9 years; 61% were women. Mean cystatin C was 1.62 mg/L with estimated glomerular filtration rate 39.2 mL/min/1.73 m². Performance on measures of global cognition, executive function, and visual-spatial ability declined at higher tertiles of cystatin C (lower kidney function). Higher cystatin C was significantly associated with infratentorial microbleeds and lower gray matter volume. Adjusted risk of incident dementia was increased in the middle and high cystatin C tertile groups compared with the low group (hazard ratio in highest tertile 3.81 [95% confidence interval 1.14-12.7]), which appeared to be explained in part by the presence of cerebral microbleeds. Overall, cystatin C was associated with cognitive performance, brain imaging pathology, and decline to dementia in this oldest-old cohort.

SUBMITTER: Lau WL

PROVIDER: S-EPMC7307913 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Cystatin C, cognition, and brain MRI findings in 90+-year-olds.

Lau Wei Ling WL Fisher Mark M Greenia Dana D Floriolli David D Fletcher Evan E Singh Baljeet B Sajjadi Seyed Ahmad SA Corrada Maria M MM Whittle Christina C Kawas Claudia C Paganini-Hill Annlia A

Neurobiology of aging 20200429

Chronic kidney disease is emerging as a novel risk factor for cerebrovascular disease, but this association remains largely unexplored in older adults. Cystatin C is a more accurate measure than creatinine of kidney function in the elderly. We evaluated cystatin C, cognitive function, and brain imaging in 193 participants from The 90+ Study neuroimaging component. The mean age was 93.9 years; 61% were women. Mean cystatin C was 1.62 mg/L with estimated glomerular filtration rate 39.2 mL/min/1.73 ...[more]

PMID: 32473464

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Project description:BackgroundThe effect of varying brain ventricular volume on the cerebrospinal fluid (CSF) proteome has been discussed as possible confounding factors in comparative protein level analyses. However, the relationship between CSF volume and protein levels remains largely unexplored. Moreover, the few existing studies provide conflicting findings, indicating the need for further research.MethodsHere, we explored the association between levels of 88 pre-selected CSF proteins and ventricular volume derived from magnetic resonance imaging (MRI) measurements in 157 cognitively healthy 70-year-olds from the H70 Gothenburg Birth Cohort Studies, including individuals with and without pathological levels of Alzheimer's disease (AD) CSF markers (n = 123 and 34, respectively). Both left and right lateral, the inferior horn as well as the third and the fourth ventricular volumes were measured. Different antibody-based methods were employed for the protein measurements, with most being analyzed using a multiplex bead-based microarray technology. Furthermore, the associations between the protein levels and cortical thickness, fractional anisotropy, and mean diffusivity were assessed.ResultsCSF levels of many brain-derived proteins correlated with ventricular volumes in A-T- individuals, with lower levels in individuals with larger ventricles. The strongest negative correlations with total ventricular volume were observed for neurocan (NCAN) and neurosecretory protein VGF (rho = -0.34 for both). Significant negative correlations were observed also for amyloid beta (Ab) 38, Ab40, total tau (t-tau), and phosphorylated tau (p-tau), with correlation ranging between - 0.34 and - 0.28, while no association was observed between ventricular volumes and Ab42 or neurofilament light chain (NfL). Proteins with negative correlations to ventricular volumes further demonstrated negative correlations to mean diffusivity and positive correlation to fractional anisotropy. However, only weak or no correlations were observed between the CSF protein levels and cortical thickness. A + T + individuals demonstrated higher CSF protein levels compared to A-T- individuals with the most significant differences observed for neurogranin (NRGN) and synuclein beta (SNCB).ConclusionsOur findings suggest that the levels of many brain-derived proteins in CSF may be subjected to dilution effects depending on the size of the brain ventricles in healthy individuals without AD pathology. This phenomenon could potentially contribute to the inter-individual variations observed in CSF proteomic studies.

Project description:ObjectivesTo examine predictors of partial and full measles, mumps and rubella (MMR) vaccination catch-up between 3 and 5 years.DesignSecondary data analysis of the nationally representative Millennium Cohort Study (MCS).SettingChildren born in the UK, 2000-2002.Participants751 MCS children who were unimmunised against MMR at age 3, with immunisation information at age 5.Main outcome measuresCatch-up status: unimmunised (received no MMR), partial catch-up (received one MMR) or full catch-up (received two MMRs).ResultsAt age 5, 60.3% (n=440) children remained unvaccinated, 16.1% (n=127) had partially and 23.6% (n=184) had fully caught-up. Children from families who did not speak English at home were five times as likely to partially catch-up than children living in homes where only English was spoken (risk ratio 4.68 (95% CI 3.63 to 6.03)). Full catch-up was also significantly more likely in those did not speak English at home (adjusted risk ratio 1.90 (1.08 to 3.32)). In addition, those from Pakistan/Bangladesh (2.40 (1.38 to 4.18)) or 'other' ethnicities (such as Chinese) (1.88 (1.08 to 3.29)) were more likely to fully catch-up than White British. Those living in socially rented (1.86 (1.34 to 2.56)) or 'Other' (2.52 (1.23 to 5.18)) accommodations were more likely to fully catch-up than home owners, and families were more likely to catch-up if they lived outside London (1.95 (1.32 to 2.89)). Full catch-up was less likely if parents reported medical reasons (0.43 (0.25 to 0.74)), a conscious decision (0.33 (0.23 to 0.48)), or 'other' reasons (0.46 (0.29 to 0.73)) for not immunising at age 3 (compared with 'practical' reasons).ConclusionsParents who partially or fully catch-up with MMR experience practical barriers and tend to come from disadvantaged or ethnic minority groups. Families who continue to reject MMR tend to have more advantaged backgrounds and make a conscious decision to not immunise early on. Health professionals should consider these findings in light of the characteristics of their local populations.

Dataset Information

Cystatin C, cognition, and brain MRI findings in 90+-year-olds.

Publications

Cystatin C, cognition, and brain MRI findings in 90+-year-olds.

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