TABLE 4.
Multivariable linear regression analyses of the associations between the HRF indices (PIP, PNNSS and PNNLS) and the cognitive scores (CASI, DSC, DS forward and DS backward) measured at exam 6.
| EXAM 6 | MODEL 1 |
MODEL 2 |
MODEL 3 |
MODEL 4 |
MODEL 5 |
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| Unadjusted | CAIDE–APOE-ε4 | Age, sex, race, education | Demographic + APOE-ε4 + CV | Model 4 + NT-proBNP | ||||||||||||||||
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and other “traditional” risk factors |
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| β | 95% CI | p | β | 95% CI | p | β | 95% CI | p | β | 95% CI | p | β | 95% CI | p | ||||||
| CASI | ||||||||||||||||||||
| PIP (7.01%) | −1.49 | −2.00 | −0.99 | <0.001 | −1.46 | −1.96 | −0.96 | <0.001 | −0.60 | −1.05 | −0.15 | 0.010 | −0.50 | −0.95 | −0.04 | 0.032 | −0.47 | −0.92 | −0.01 | 0.045 |
| PNNSS (13.7%) | −1.53 | −2.05 | −1.01 | <0.001 | −1.43 | −1.93 | −0.92 | <0.001 | −0.68 | −1.15 | −0.21 | 0.005 | −0.61 | −1.07 | −0.14 | 0.010 | −0.57 | −1.03 | −0.10 | 0.018 |
| PNNLS (12.6%) | 1.54 | 1.02 | 2.06 | <0.001 | 1.44 | 0.94 | 1.95 | <0.001 | 0.69 | 0.22 | 1.16 | 0.004 | 0.57 | 0.11 | 1.02 | 0.015 | 0.52 | 0.06 | 0.98 | 0.026 |
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| DSC | ||||||||||||||||||||
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| PIP (6.95%) | −4.28 | −5.37 | −3.19 | <0.001 | −4.21 | −5.29 | −3.13 | <0.001 | −1.37 | −2.29 | −0.44 | 0.004 | −1.17 | −2.17 | −0.18 | 0.021 | −1.16 | −2.15 | −0.16 | 0.023 |
| PNNSS (13.7%) | −3.91 | −5.01 | −2.80 | <0.001 | −3.67 | −4.77 | −2.57 | <0.001 | −1.60 | −2.51 | −0.69 | 0.001 | −1.54 | −2.54 | −0.54 | 0.003 | −1.55 | −2.56 | −0.54 | 0.003 |
| PNNLS (12.6%) | 3.97 | 2.86 | 5.08 | <0.001 | 3.75 | 2.65 | 4.86 | <0.001 | 1.59 | 0.68 | 2.51 | 0.001 | 1.46 | 0.47 | 2.45 | 0.004 | 1.47 | 0.48 | 2.47 | 0.004 |
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| DS forward | ||||||||||||||||||||
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| PIP (7.09%) | −0.29 | −0.44 | −0.13 | <0.001 | −0.26 | −0.42 | −0.11 | 0.001 | −0.16 | −0.31 | 0.00 | 0.049 | −0.15 | −0.31 | 0.02 | 0.084 | −0.16 | −0.32 | 0.01 | 0.064 |
| PNNSS (13.7%) | −0.25 | −0.41 | −0.09 | 0.002 | −0.22 | −0.38 | −0.06 | 0.008 | −0.15 | −0.30 | 0.00 | 0.057 | −0.14 | −0.31 | 0.02 | 0.092 | −0.16 | −0.33 | 0.01 | 0.064 |
| PNNLS (12.6%) | 0.26 | 0.10 | 0.42 | 0.002 | 0.23 | 0.07 | 0.39 | 0.006 | 0.15 | 0.00 | 0.31 | 0.051 | 0.14 | −0.02 | 0.31 | 0.092 | 0.16 | −0.01 | 0.32 | 0.062 |
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| DS backward | ||||||||||||||||||||
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| PIP (7.09%) | −0.30 | −0.43 | −0.17 | <0.001 | −0.28 | −0.40 | −0.15 | <0.001 | −0.14 | −0.26 | −0.01 | 0.037 | −0.16 | −0.30 | −0.03 | 0.019 | −0.16 | −0.29 | −0.02 | 0.024 |
| PNNSS (13.7%) | −0.29 | −0.43 | −0.16 | <0.001 | −0.26 | −0.39 | −0.12 | <0.001 | −0.13 | −0.25 | −0.01 | 0.039 | −0.17 | −0.31 | −0.04 | 0.009 | −0.18 | −0.31 | −0.05 | 0.009 |
| PNNLS (12.6%) | 0.30 | 0.16 | 0.43 | <0.001 | 0.26 | 0.13 | 0.40 | <0.001 | 0.13 | 0.01 | 0.26 | 0.030 | 0.17 | 0.04 | 0.30 | 0.010 | 0.17 | 0.04 | 0.30 | 0.010 |
Values presented are the standardized ß regression coefficients and 95% CIs. Model 1 was unadjusted. Model 2 was adjusted for the CAIDE–APOE-ε4 risk index. Model 3 was adjusted for age, race/ethnicity, sex, and level of education attained. Model 4 included the variables of Model 3 in addition to prevalent CV and AF events, CV risk factors (usage of anti-hypertensive and lipid lowering medications, systolic BP, diabetes mellitus status, total cholesterol, high-density lipoprotein cholesterol, pack-years of cigarette smoking), alcohol consumption, weekly amounts of moderate and vigorous physical activity, depression, usage of antidepressant medications, total gross family income ≥ $75,000 and mean HR. Model 5 included the variables of Model 4 and NT-proBNP. The value in parenthesis after each independent variable (PIP, PNNSS and PNNLS) is its SD. Statistically significant associations (p value < 0.05) are highlighted in bold. Borderline significant associations (0.05≤p value ≤0.1) are highlighted using bold, italicized and underlined fonts.
AF, atrial fibrillation; BP, blood pressure; CAIDE, Cardiovascular Risk Factors, Aging, and Incidence of Dementia; CASI, the Cognitive Abilities Screening Instrument score; CI, confidence interval; CV, cardiovascular; DS, digit span; DSC, digit symbol coding; HR, heart rate; HRF, heart rate fragmentation; PIP, percentage of inflection points; PNNLS, percentage of NN intervals in long (≥3) accelerative/decelerative segments; PNNSS, percentage of NN intervals in short (<3) accelerative/decelerative segments; NT-proBNP, N-terminal prohormone B-type natriuretic peptide.