TY - JOUR
T1 - Sex-dependent effects of cardiometabolic health and APOE4 on brain age
T2 - A longitudinal cohort study
AU - Subramaniapillai, Sivaniya
AU - Schindler, Louise S.
AU - Redmond, Paul
AU - Bastin, Mark E
AU - Wardlaw, Joanne M.
AU - Valdés Hernández, Maria C
AU - Muñoz Maniega, Susana
AU - Aribisala, Benjamin
AU - Westlye, Lars T
AU - Coath, William
AU - Groves, James
AU - Cash, David M.
AU - Barnes, Josephine
AU - James, Sarah-Naomi
AU - Sudre, Carole H.
AU - Barkhof, Frederik
AU - Richards, Marcus
AU - Corley, Janie
AU - Russ, Tom
AU - Cox, Simon R.
AU - Schott, Jonathan M
AU - Cole, James H.
AU - de Lange, Ann-Marie G.
N1 - Sivaniya Subramaniapillai: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data; Louise Schindler: Drafting/revision of the manuscript for content, including medical writing for content; Analysis or interpretation of data; Paul Redmond: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Mark Bastin: Drafting/revision of the manuscript for content, including medical writing for content; Joanna Wardlaw: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Maria Valdés Hernández: Drafting/revision of the manuscript for content, including medical writing for content; Susana Muñoz Maniega: Drafting/revision of the manuscript for content, including medical writing for content; Benjamin Aribisala: Drafting/revision of the manuscript for content, including medical writing for content; Lars T. Westlye: Drafting/revision of the manuscript for content, including medical writing for content; Analysis or interpretation of data; William Coath: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; James Groves: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; David Cash: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Josephine Barnes: Drafting/revision of the manuscript for content, including medical writing for content; Sarah-Naomi James: Drafting/revision of the manuscript for content, including medical writing for content; Carole Sudre: Drafting/revision of the manuscript for content, including medical writing for content; Frederik Barkhof: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Marcus Richards: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Janie Corley: Drafting/revision of the manuscript for content, including medical writing for content; Tom Russ: Drafting/revision of the manuscript for content, including medical writing for content; Simon Cox: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Jonathan Schott: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; James Cole: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data; Ann-Marie de Lange: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data;
PY - 2024/9/24
Y1 - 2024/9/24
N2 - Background and Objectives: The aging population is growing faster than all other demographicstrata. With older age comes a greater risk of health conditions such as obesity and high blood pressure(BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging,yet their influence on brain health in females versus males remains largely unexplored. In this study, weinvestigated sex differences in relationships between BP, body mass index (BMI), and brain age over time,and tested for interactions with apolipoprotein E-ϵ4 genotype (APOE4), a known genetic risk factor forAlzheimer's disease. Methods: The sample included participants from two UK-based longitudinal birthcohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at leastone timepoint were included to evaluate sex differences in associations between CMRs and brain age. Theopen-access software package brainageR 2.1 was used to estimate brain age for each participant. Linearmixed effects models were used to assess the relationships between brain age, BMI, BP, and APOE4status (i.e., carrier vs. non-carrier) in males and females over time. Results: The combined samplecomprised 1120 participants (48% female) with mean age (SD) at the timepoint 1 assessment = 73 (0.72)years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46. Approximately 30% of participantswere APOE4 carriers. Higher systolic and diastolic BP was significantly associated with older brain age infemales only (β = 0.43-0.56, p < 0.05). Among males, higher BMI was associated with older brain ageacross timepoints and APOE4 groups (β = 0.72-0.77, p < 0.05). In females, higher BMI was linked toolder brain age among APOE4 non-carriers (β = 0.68-0.99, p < 0.05), while higher BMI was linked toyounger brain age among carriers, particularly at the last timepoint (β = -1.75, p < 0.05). Discussion: Thisstudy indicates sex and time-dependent relationships between CMRs, APOE4 status, and brain age. Ourfindings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individualagingtrajectories, providing a basis for developing personalized preventive interventions.
AB - Background and Objectives: The aging population is growing faster than all other demographicstrata. With older age comes a greater risk of health conditions such as obesity and high blood pressure(BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging,yet their influence on brain health in females versus males remains largely unexplored. In this study, weinvestigated sex differences in relationships between BP, body mass index (BMI), and brain age over time,and tested for interactions with apolipoprotein E-ϵ4 genotype (APOE4), a known genetic risk factor forAlzheimer's disease. Methods: The sample included participants from two UK-based longitudinal birthcohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at leastone timepoint were included to evaluate sex differences in associations between CMRs and brain age. Theopen-access software package brainageR 2.1 was used to estimate brain age for each participant. Linearmixed effects models were used to assess the relationships between brain age, BMI, BP, and APOE4status (i.e., carrier vs. non-carrier) in males and females over time. Results: The combined samplecomprised 1120 participants (48% female) with mean age (SD) at the timepoint 1 assessment = 73 (0.72)years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46. Approximately 30% of participantswere APOE4 carriers. Higher systolic and diastolic BP was significantly associated with older brain age infemales only (β = 0.43-0.56, p < 0.05). Among males, higher BMI was associated with older brain ageacross timepoints and APOE4 groups (β = 0.72-0.77, p < 0.05). In females, higher BMI was linked toolder brain age among APOE4 non-carriers (β = 0.68-0.99, p < 0.05), while higher BMI was linked toyounger brain age among carriers, particularly at the last timepoint (β = -1.75, p < 0.05). Discussion: Thisstudy indicates sex and time-dependent relationships between CMRs, APOE4 status, and brain age. Ourfindings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individualagingtrajectories, providing a basis for developing personalized preventive interventions.
KW - cardiometabolic risk
KW - sex differences
KW - brain age
KW - APOE4 risk
KW - longitudinal
U2 - 10.1212/WNL.0000000000209744
DO - 10.1212/WNL.0000000000209744
M3 - Article
C2 - 39173100
SN - 0028-3878
VL - 103
JO - Neurology
JF - Neurology
IS - 6
M1 - e209744
ER -