TY - JOUR
T1 - VASCULAR AND EARLY LIFE INFLUENCES ON CEREBROVASCULAR DISEASE IN INSIGHT 46: A SUB-STUDY OF THE MRC NATIONAL SURVEY OF HEALTH AND DEVELOPMENT (NSHD) BRITISH BIRTH COHORT
AU - Lane, Christopher A.
AU - Sudre, Carole H.
AU - Barnes, Josephine
AU - Nicholas, Jennifer M.
AU - Parker, Thomas
AU - Cash, David M.
AU - Murray-Smith, Heidi
AU - Wong, Andrew
AU - Malone, Ian B.
AU - Klimova, Jana
AU - Kuh, Diana
AU - Ourselin, Sebastien
AU - Cardoso, M. Jorge
AU - Richards, Marcus
AU - Fox, Nick C.
AU - Schott, Jonathan M.
PY - 2017/10/20
Y1 - 2017/10/20
N2 - Background: Early life characteristics influence many aspects of health in later life. Their association with, and pathways through which they affect brain health, are less well understood. We performed an exploratory analysis in a community based sample aged 70 years, mainly free of clinical dementia, investigating the relationships of cerebrovascular disease (CVD) with vascular risk factors (VRFs), amyloid (Ab) burden and childhood cognitive ability, educational attainment, and lifetime socioeconomic position (SEP). Methods: Participants were recruited to Insight 46, a neuroscience sub-study of the MRC NSHD, a cohort of individuals born in mainland Britain in the same week in 1946. Childhood cognitive ability (standardised score), years of education (by age 26) and lifetime SEP (based on father's and own occupational class) have been collected prospectively. We included 203 participants with multimodal (including volumetric T1-T2-and FLAIR) magnetic resonance imaging (MRI) and florbetapir amyloid PET imaging in this interim analysis. An automated algorithm based on a multivariate Gaussian mixture model was used to delineate white matter hyperintensities (WMH) from the multi-modal MRI (figure). Abpositivity was defined as a cortical grey matter: cerebellar standard uptake value ratio (SUVR)>1.078. Multiple linear regression was used with log-transformed WMH volume (WMHV) as the dependent variable and adjustment for gender, head size, ApoE4 allele number applied to each model to assess associations between: (1) cross-sectional VRFs (see Table) and WMHV; (2)amyloid burden and WMHV, accounting for VRFs; (3)childhood cognitive ability, educational attainment, SEP, and WMHV, accounting for VRFs. Results: Sample characteristics are shown in the Table. At age 70 higher diastolic blood pressure (DBP) (mmHg) was associated with greater WMHV (model 3:b1/40.032;p1/40.008), as was female gender (model 3:b1/40.71;p1/40.042). Higher childhood cognitive ability was associated with lower WMHV (model 3:b1/4- 0.40;p1/40.011). There was no significant association between Ab status and WMHV; or between educational attainment, child or adult SEP and WMHV. Conclusions:We observed positive associations between DBP, female gender and WMHV, and a negative association with childhood cognitive ability which was not mediated by conventional VRF, nor attenuated by adjustment for SEP or educational attainment. Future work will investigate the mechanisms by which childhood cognitive ability and gender influence CVD in later life. (Table Presented).
AB - Background: Early life characteristics influence many aspects of health in later life. Their association with, and pathways through which they affect brain health, are less well understood. We performed an exploratory analysis in a community based sample aged 70 years, mainly free of clinical dementia, investigating the relationships of cerebrovascular disease (CVD) with vascular risk factors (VRFs), amyloid (Ab) burden and childhood cognitive ability, educational attainment, and lifetime socioeconomic position (SEP). Methods: Participants were recruited to Insight 46, a neuroscience sub-study of the MRC NSHD, a cohort of individuals born in mainland Britain in the same week in 1946. Childhood cognitive ability (standardised score), years of education (by age 26) and lifetime SEP (based on father's and own occupational class) have been collected prospectively. We included 203 participants with multimodal (including volumetric T1-T2-and FLAIR) magnetic resonance imaging (MRI) and florbetapir amyloid PET imaging in this interim analysis. An automated algorithm based on a multivariate Gaussian mixture model was used to delineate white matter hyperintensities (WMH) from the multi-modal MRI (figure). Abpositivity was defined as a cortical grey matter: cerebellar standard uptake value ratio (SUVR)>1.078. Multiple linear regression was used with log-transformed WMH volume (WMHV) as the dependent variable and adjustment for gender, head size, ApoE4 allele number applied to each model to assess associations between: (1) cross-sectional VRFs (see Table) and WMHV; (2)amyloid burden and WMHV, accounting for VRFs; (3)childhood cognitive ability, educational attainment, SEP, and WMHV, accounting for VRFs. Results: Sample characteristics are shown in the Table. At age 70 higher diastolic blood pressure (DBP) (mmHg) was associated with greater WMHV (model 3:b1/40.032;p1/40.008), as was female gender (model 3:b1/40.71;p1/40.042). Higher childhood cognitive ability was associated with lower WMHV (model 3:b1/4- 0.40;p1/40.011). There was no significant association between Ab status and WMHV; or between educational attainment, child or adult SEP and WMHV. Conclusions:We observed positive associations between DBP, female gender and WMHV, and a negative association with childhood cognitive ability which was not mediated by conventional VRF, nor attenuated by adjustment for SEP or educational attainment. Future work will investigate the mechanisms by which childhood cognitive ability and gender influence CVD in later life. (Table Presented).
UR - http://www.mendeley.com/research/vascular-early-life-influences-cerebrovascular-disease-insight-46-substudy-mrc-national-survey-healt
U2 - 10.1016/j.jalz.2017.06.1203
DO - 10.1016/j.jalz.2017.06.1203
M3 - Article
SN - 1552-5260
VL - 13
SP - P851-P853
JO - Alzheimer's & Dementia
JF - Alzheimer's & Dementia
IS - 7
ER -
