Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936

Abstract

It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study.

The relation between total cerebral small vessel disease burden and gait impairment in patients with minor stroke

“…There is increasing evidence that a total cSVD MRI burden score, which summarizes individual cSVD markers in a compound scale, might better reflect the global overall effect of cSVD on the brain. [11][12][13][14]20,21 A study 22 in older subjects with vascular risk factors showed that concurrent gait function, measured by Unified Parkinson's Disease Rating Scale, 23 was associated with total cSVD burden. This was the first study looking at concurrent gait function and overall cSVD burden (but not after stroke), although the cSVD burden score was incomplete as they did not include PVS.…”

Advanced Neuroimaging of Cerebral Small Vessel Disease

“…Initial efforts were further tested and refined in larger datasets of patients with stroke and healthy older individuals, testing inclusion of additional features and different weighting of individual feature scores, with the Edinburgh group [11, 17, 18]. In the current version of the score, a point is attributed for each of the following: moderate to severe WMH, presence of moderate to severe PVS in the basal ganglia, presence of lacunes and presence of microbleeds.…”

“…From the attempts to devise a composite SVD score representative of the individual’s SVD burden, a major effort has been made by Staals and colleagues [ 27 •], based on visually rated individual SVD features and combines them into the ‘total SVD burden’ on a scale of 0–4 [ 27 •]. Initial efforts were further tested and refined in larger datasets of patients with stroke and healthy older individuals, testing inclusion of additional features and different weighting of individual feature scores, with the Edinburgh group [ 11 , 17 , 18 ]. In the current version of the score, a point is attributed for each of the following: moderate to severe WMH, presence of moderate to severe PVS in the basal ganglia, presence of lacunes and presence of microbleeds.…”

“…Total SVD burden measures have also been associated with emerging SVD risk factors. These include early life factors such as age 11 IQ, childhood deprivation, education and class of occupation in the LBC1936 [ 17 ]. Pulse wave velocity (PWV, a marker of arterial stiffness) which has previously been repeatedly shown to correlate with WMH has shown similar associations with a composite SVD score [ 16 ].…”

Hippocampal morphology and cognitive functions in community-dwelling older people: the Lothian Birth Cohort 1936

“…In line with the studies referenced above, we hypothesize that in this cohort of septuagenarian individuals' hippocampal morphology, and specifically lateral deformations on the surface of the hippocampal head, will be associated with specific memory ability and also with broader cognitive domains. Given prior evidence in the hippocampus (Tang et al., 2016) and associations between earlier life intelligence and other MRI phenotypes in this cohort (e.g., Cox et al., 2016, Field et al., 2016), we further hypothesize that precursors of these deformations could be found at childhood.…”