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BACKGROUND: Sleep is thought to play a major role in brain health and general wellbeing. However, few longitudinal studies have explored the relationship between sleep habits and imaging markers of brain health, particularly markers of brain waste clearance such as perivascular spaces (PVS), of neurodegeneration such as brain atrophy, and of vascular disease, such as white matter hyperintensities (WMH). We explore these associations using data collected over 6 years from a birth cohort of older community-dwelling adults in their 70s.METHOD: We analysed brain MRI data from ages 73, 76 and 79 years, and self-reported sleep duration, sleep quality and vascular risk factors from community-dwelling participants in the Lothian Birth Cohort 1936 (LBC1936) study. We calculated sleep efficiency (at age 76), quantified PVS burden (at age 73), and WMH and brain volumes (age 73 to 79), calculated the white matter damage metric, and used structural equation modelling (SEM) to explore associations and potential causative pathways between indicators related to brain waste cleaning (i.e., sleep and PVS burden), brain and WMH volume changes during the 8th decade of life.RESULTS: Lower sleep efficiency was associated with a reduction in normal-appearing white matter (NAWM) volume (β = 0.204, P = 0.009) from ages 73 to 79, but not concurrent volume (i.e. age 76). Increased daytime sleep correlated with less night-time sleep (r = -0.20, P < 0.001), and with increasing white matter damage metric (β = -0.122, P = 0.018) and faster WMH growth (β = 0.116, P = 0.026). Shorter night-time sleep duration was associated with steeper 6-year reduction of NAWM volumes (β = 0.160, P = 0.011). High burden of PVS at age 73 (volume, count, and visual scores), was associated with faster deterioration in white matter: reduction of NAWM volume (β = -0.16, P = 0.012) and increasing white matter damage metric (β = 0.37, P < 0.001) between ages 73 and 79. On SEM, centrum semiovale PVS burden mediated 5% of the associations between sleep parameters and brain changes.CONCLUSION: Sleep impairments, and higher PVS burden, a marker of impaired waste clearance, were associated with faster loss of healthy white matter and increasing WMH in the 8th decade of life. A small percentage of the effect of sleep in white matter health was mediated by the burden of PVS consistent with the proposed role for sleep in brain waste clearance.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221135658 for Retinal capillary microvessel morphology changes are associated with vascular damage and dysfunction in cerebral small vessel disease by Stewart J Wiseman, Jun-Fang Zhang, Calum Gray, Charlene Hamid, Maria del C Valdés Hernández, Lucia Ballerini, Michael J Thrippleton, Cameron Manning, Michael Stringer, Emilie Sleight, Susana Muñoz Maniega, Alasdair Morgan, Yajun Cheng, Carmen Arteaga, Dany Jaime Garcia, Una Clancy, Fergus N Doubal, Baljean Dhillon, Tom MacGillivray, Yun-Cheng Wu and Joanna M Wardlaw in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221135658 for Retinal capillary microvessel morphology changes are associated with vascular damage and dysfunction in cerebral small vessel disease by Stewart J Wiseman, Jun-Fang Zhang, Calum Gray, Charlene Hamid, Maria del C Valdés Hernández, Lucia Ballerini, Michael J Thrippleton, Cameron Manning, Michael Stringer, Emilie Sleight, Susana Muñoz Maniega, Alasdair Morgan, Yajun Cheng, Carmen Arteaga, Dany Jaime Garcia, Una Clancy, Fergus N Doubal, Baljean Dhillon, Tom MacGillivray, Yun-Cheng Wu and Joanna M Wardlaw in Journal of Cerebral Blood Flow & Metabolism

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single-molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing–remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation and neurite orientation dispersion and density imaging diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 versus 0.57, difference 0.036, 95% CI: 0.029–0.043, P < 0.001). Lesion volume (Spearman’s rho rs= 0.38, P < 0.001) and g-ratio (rs= 0.24, P < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) [11/23 (48%) versus 2/15 (13%), P < 0.05]. These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity and help to identify individuals with a high degree of axonal damage at disease onset., York et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing–remitting multiple sclerosis patients at diagnosis using advanced MRI and single-molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament., Graphical Abstract Graphical Abstract

Supplemental material, sj-pdf-1-lup-10.1177_0961203320979045 for Brain network reorganisation and spatial lesion distribution in systemic lupus erythematosus by Maria del C Valdés Hernández, Keith Smith, Mark E Bastin, E. Nicole Amft, Stuart H Ralston, Joanna M Wardlaw and Stewart J Wiseman in Lupus

Supplemental material, sj-pdf-2-eso-10.1177_2396987320929617 for Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3 by Una Clancy, Daniela Jaime Garcia, Michael S Stringer, Michael J Thrippleton, Maria C Valdés-Hernández, Stewart Wiseman, Olivia KL Hamilton, Francesca M Chappell, Rosalind Brown, Gordon W Blair, Will Hewins, Emilie Sleight, Lucia Ballerini, Mark E Bastin, Susana Munoz Maniega, Tom MacGillivray, Kirstie Hetherington, Charlene Hamid, Carmen Arteaga, Alasdair G Morgan, Cameron Manning, Ellen Backhouse, Iona Hamilton, Dominic Job, Ian Marshall, Fergus N Doubal and Joanna M Wardlaw in European Stroke Journal

Supplemental material, sj-pdf-1-lup-10.1177_0961203320979045 for Brain network reorganisation and spatial lesion distribution in systemic lupus erythematosus by Maria del C Valdés Hernández, Keith Smith, Mark E Bastin, E. Nicole Amft, Stuart H Ralston, Joanna M Wardlaw and Stewart J Wiseman in Lupus

Supplemental material, sj-pdf-1-eso-10.1177_2396987320929617 for Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3 by Una Clancy, Daniela Jaime Garcia, Michael S Stringer, Michael J Thrippleton, Maria C Valdés-Hernández, Stewart Wiseman, Olivia KL Hamilton, Francesca M Chappell, Rosalind Brown, Gordon W Blair, Will Hewins, Emilie Sleight, Lucia Ballerini, Mark E Bastin, Susana Munoz Maniega, Tom MacGillivray, Kirstie Hetherington, Charlene Hamid, Carmen Arteaga, Alasdair G Morgan, Cameron Manning, Ellen Backhouse, Iona Hamilton, Dominic Job, Ian Marshall, Fergus N Doubal and Joanna M Wardlaw in European Stroke Journal

Research involving brain imaging is important for understanding common brain diseases. Study endpoints can include features and measures derived from imaging modalities, providing a benchmark against which other phenotypical data can be assessed. In trials, imaging data provides objective evidence of beneficial and adverse outcomes. Multi-centre studies increase generalizability and statistical power. However, there is a lack of practical guidelines for the set-up and conduct of large neuroimaging studies. We address this deficit by describing aspects of study design and other essential practical considerations that will help researchers avoid common pitfalls and data loss. The recommendations are grouped as: 1. Get help from experts in the field and plan the study, 2. Define the imaging endpoints, develop an imaging manual and have a system in place to manage the workflow, 3. Perform a dummy run test scan and test the analysis methods, 4. Acquire the scans, 5. Data anonymisation and transfer, 6. Quality control, 7. Data sharing. Implementing these steps will lead to valuable and usable data and help avoid imaging data wastage. Additionally, we highlight the importance of data sharing to maximize the benefits of the research to society by making the data available to other researchers.