Introduction
Methods
Participants
Cognitive outcomes
Type 2 diabetes, HbA1c and insulin resistance
PRSs of traits
Earlier-life variables (covariables)
Statistical analysis
Sensitivity analyses
Results
Characteristic | Mean (SD)a, all | Participants available | |
---|---|---|---|
n
| % | ||
Sex (male), % | 48 | 1803 | 100 |
Higher childhood SEP, % | 47 | 1737 | 96 |
Higher educational attainment, % | 40 | 1759 | 98 |
Child cognition SD, age 8 years | 0.13 (0.8) | 1628 | 90 |
Known T2DM by age 69 years, n (%) | 169 (10) | 1701 | 94 |
HbA1c at age 69 years | |||
% | 5.8 (0.6) | 1486 | 82 |
mmol/mol | 40 (6.6) | 1486 | 82 |
Ever on diabetes medication, n (%) | 128 (7.3) | 1803 | 100 |
Smoking status (never/ex/current), % | 30, 61, 8 | 1782 | 99 |
Characteristics at age 69 years | |||
WHR | |||
Men | 0.96 (0.07) | 856 | 47 |
Women | 0.87 (0.07) | 936 | 52 |
BMI, kg/m2 | 28.0 (5.1) | 1789 | 99 |
BP, mmHg | |||
Systolic | 132 (16) | 1793 | 99 |
Diastolic | 73 (10) | 1793 | 99 |
Heart rate, bpm | 68.8 (10.9) | 1794 | 100 |
Total cholesterol, mmol/l | 5.2 (1.2) | 1521 | 84 |
HDL-cholesterol, mmol/l | 1.5 (0.4) | 1515 | 84 |
LDL-cholesterol, mmol/l | 2.9 (0.9) | 1499 | 83 |
Triacylglycerols, median (IQR), mmol/l | 1.5 (1.1–2) | 1521 | 84 |
Alcohol (≥×4/week), n (%) | 507 (30) | 1789 | 99 |
Clinical history, any incidence, n (%) | |||
Stroke | 69 (4) | 1797 | 100 |
Angina | 113 (7) | 1797 | 100 |
Heart attack | 65 (4) | 1797 | 100 |
Heart failure | 42 (3) | 1797 | 100 |
Prior cardiac event | 218 (13) | 1797 | 100 |
APOE-ε4b (absent, hetero-, homozygous), % | (71, 25, 3) | 1582 | 88 |
Mid-life T2DM measures at age 60–64 years | |||
Known T2DM, n (%) | 101 (7) | 1799 | 100 |
HbA1c | |||
% | 5.8 (0.7) | 1671 | 93 |
mmol/mol | 40 (7.7) | 1671 | 93 |
HOMA2-IR | 0.9 (0.6) | 1379 | 76 |
Later-life cognitive measures, age 69 years | |||
ACE-III (max score = 100) | 91.5 (5.9) | 1494 | 83 |
Verbal memory score (max score = 45) | 22.3 (6.1) | 1780 | 99 |
Associations with PRSs
PRS exposure | Unweighted PRS | Externally weighted PRS | ||||
---|---|---|---|---|---|---|
β/ORa |
p
| 95% CI | β/ORa |
p
| 95% CI | |
Type 2 diabetes PRS predictor | ||||||
Known T2DM at age 60–64 yearsa | 1.08 | <0.001 | 1.03, 1.11 | 1.45 | <0.01 | 1.10, 1.84 |
HOMA2-IR at age 60–64 years | 0.11 | <0.001 | 0.01, 0.16 | 0.08 | 0.01 | 0.02, 0.16 |
HbA1c at age 60–64 years | 0.12 | <0.001 | 0.02, 0.17 | 0.14 | <0.001 | 0.11, 0.28 |
ACE-III at age 69 years | 0.02 | 0.39 | −0.03, 0.08 | 0.04 | 0.15 | −0.02, 0.90 |
Verbal memory at age 69 years | −0.01 | 0.72 | −0.07, 0.05 | 0.001 | 0.96 | −0.38, 0.36 |
Insulin resistance PRS predictor | ||||||
ACE-III at age 69 years | 0.04 | 0.25 | −0.07, 0.09 | 0.03 | 0.12 | −0.04, 0.56 |
Verbal memory at age 69 years | −0.01 | 0.83 | −0.08, 0.09 | −0.01 | 0.81 | −0.39, 0.24 |
Hyperglycaemia PRS predictor | ||||||
ACE-III at age 69 years | 0.02 | 0.42 | −0.04, 0.05 | 0.03 | 0.24 | −0.07, 0.41 |
Verbal memory at age 69 years | −0.001 | 0.79 | −0.13, 0.12 | −0.01 | 0.81 | −0.51, 0.19 |