Table 3. Linear Mixed Model Regression Coefficients to Investigate the Association of Risk Factors With Levels of Cognitive Performance Aggregated Over the Study Perioda.
| Models | Global cognition | Memory | Executive functions | Verbal fluency | Visuospatial functions | Attention/processing speed | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β (95% CI) | P value | β (95% CI) | P value | β (95% CI) | P value | β (95% CI) | P value | β (95% CI) | P value | β (95% CI) | P value | |
| Age | −0.02 (−0.06 to 0.02) | .26 | −0.03 (−0.08 to 0.03) | .33 | −0.04 (−0.08 to 0.00) | .06 | −0.02 (−0.08 to 0.04) | .52 | −0.01 (−0.06 to 0.03) | .53 | 0 (−0.05 to 0.04) | .84 |
| Men | 0.05 (−0.08 to 0.18) | .43 | 0.10 (−0.09 to 0.29) | .30 | 0.06 (−0.07 to 0.19) | .38 | −0.13 (−0.33 to 0.07) | .21 | 0.10 (−0.04 to 0.25) | .17 | 0.13 (−0.01 to 0.27) | .07 |
| APOE ε4 | −0.11 (−0.27 to 0.05) | .19 | −0.26 (−0.51 to −0.02) | .04 | −0.07 (−0.23 to 0.09) | .38 | −0.08 (−0.32 to 0.17) | .53 | 0.04 (−0.15 to 0.22) | .71 | −0.14 (−0.31 to 0.03) | .12 |
| APOE ε2 | 0.09 (−0.05 to 0.24) | .21 | 0.16 (−0.05 to 0.38) | .14 | 0.08 (−0.06 to 0.22) | .26 | 0.10 (−0.12 to 0.31) | .38 | 0.11 (−0.05 to 0.27) | .19 | −0.01 (−0.16 to 0.14) | .88 |
| Factors of physical health | ||||||||||||
| Independent living situation | 0.21 (0.09 to 0.32) | .001b | 0.26 (0.09 to 0.43) | .003b | 0.13 (0.01 to 0.24) | .04 | 0.33 (0.16 to 0.51) | <.001b | 0.15 (0.02 to 0.28) | .02 | 0.17 (0.04 to 0.29) | .008b |
| Good hearing | 0.13 (0.01 to 0.25) | .03 | 0.09 (−0.08 to 0.26) | .30 | 0.06 (−0.06 to 0.18) | .31 | 0.16 (−0.02 to 0.34) | .08 | 0.12 (−0.01 to 0.25) | .08 | 0.18 (0.06 to 0.31) | .005b |
| Good vision | 0.20 (0.08 to 0.33) | .001b | 0.13 (−0.05 to 0.30) | .17 | 0.21 (0.08 to 0.33) | .001b | 0.12 (−0.07 to 0.30) | .21 | 0.15 (0.02 to 0.29) | .03 | 0.38 (0.24 to 0.51) | <.001b |
| Barthel Index, ADL independence | 0.37 (0.24 to 0.49) | <.001b | 0.39 (0.20 to 0.57) | <.001b | 0.27 (0.14 to 0.40) | <.001b | 0.55 (0.36 to 0.73) | <.001b | 0.35 (0.20 to 0.49) | <.001b | 0.25 (0.11 to 0.38) | .001b |
| Previous stroke or TIA | −0.12 (−0.25 to 0.01) | .07 | −0.16 (−0.35 to 0.03) | .10 | −0.09 (−0.22 to 0.04) | .18 | −0.20 (−0.40 to −0.00) | .05 | −0.04 (−0.18 to 0.11) | .62 | −0.07 (−0.20 to 0.07) | .35 |
| Hypertension | 0.05 (−0.08 to 0.17) | .48 | 0.05 (−0.13 to 0.23) | .58 | 0.04 (−0.08 to 0.17) | .49 | 0.05 (−0.14 to 0.24) | .64 | 0.08 (−0.06 to 0.22) | .25 | 0.06 (−0.08 to 0.19) | .40 |
| Grip strength | 0.02 (0.00 to 0.03) | .04 | 0.02 (0.00 to 0.04) | .03 | 0.01 (−0.00 to 0.03) | .16 | 0.03 (0.00 to 0.05) | .03 | 0.02 (−0.00 to 0.03) | .07 | −0.00 (−0.02 to 0.01) | .67 |
| Factors of cognitive reserve | ||||||||||||
| ≥Postsecondary, nontertiary education | 0.41 (0.29 to 0.53) | <.001b | 0.31 (0.14 to 0.48) | <.001b | 0.47 (0.35 to 0.59) | <.001b | 0.46 (0.28 to 0.64) | <.001b | 0.26 (0.12 to 0.39) | <.001b | 0.50 (0.37 to 0.63) | <.001b |
| Premorbid IQ | 0.02 (0.01 to 0.02) | <.001b | 0.02 (0.01 to 0.03) | <.001b | 0.02 (0.01 to 0.02) | <.001b | 0.02 (0.01 to 0.03) | <.001b | 0.02 (0.01 to 0.02) | <.001b | 0.02 (0.01 to 0.02) | <.001b |
| Lifetime cognitive activity | 0.01 (0.00 to 0.01) | .008b | 0.01 (0.00 to 0.02) | .02 | 0.00 (−0.00 to 0.01) | .14 | 0.01 (−0.00 to 0.01) | .07 | 0.01 (0.00 to 0.01) | .02 | 0.01 (0.00 to 0.01) | .008b |
| Current cognitive activity | 0.04 (0.02 to 0.06) | <.001b | 0.04 (0.02 to 0.07) | .001b | 0.03 (0.01 to 0.05) | .001b | 0.06 (0.04 to 0.08) | <.001b | 0.03 (0.01 to 0.05) | .003b | 0.04 (0.02 to 0.05) | <.001b |
| AD-associated neuropathologies | ||||||||||||
| Aß (Thal phase) | −0.05 (−0.15 to 0.06) | .40 | −0.09 (−0.26 to 0.09) | .35 | −0.09 (−0.21 to 0.04) | .18 | 0.02 (−0.15 to 0.19) | .84 | −0.07 (−0.20 to 0.05) | .27 | −0.02 (−0.12 to 0.08) | .68 |
| NFTs (Braak stage) | −0.17 (−0.38 to 0.03) | .10 | −0.22 (−0.56 to 0.11) | .20 | −0.22 (−0.45 to 0.02) | .08 | −0.01 (−0.35 to 0.32) | .93 | −0.29 (−0.52 to −0.06) | .02 | −0.12 (−0.31 to 0.08) | .25 |
| NPs | ||||||||||||
| CERAD score 1 | −0.05 (−0.42 to 0.31) | .77 | −0.00 (−0.60 to 0.59) | .99 | −0.14 (−0.56 to 0.27) | .51 | 0.14 (−0.45 to 0.72) | .65 | −0.24 (−0.67 to 0.18) | .27 | −0.07 (−0.42 to 0.29) | .72 |
| CERAD score 2 | −0.22 (−0.62 to 0.18) | .30 | −0.22 (−0.88 to 0.43) | .51 | −0.36 (−0.81 to 0.10) | .14 | −0.00 (−0.64 to 0.64) | .99 | −0.32 (−0.78 to 0.14) | .18 | −0.19 (−0.56 to 0.19) | .34 |
Abbreviations: AD, Alzheimer disease; ADL, activities of daily living; Aβ, amyloid-β; CERAD, Consortium to Establish a Registry for Alzheimer disease; NFTs, neurofibrillary tangles; NPs, neuritic plaques; TIA, transient ischemic attack.
Separate linear mixed models including a random intercept adjusted for sex, age, education, and vision and hearing capacities. Models on verbal fluency were only adjusted for hearing capacities. A random slope was not included. There were missing data on APOE ε allele (44 participants), vision (8 participants), hearing (4 participants), Barthel Index (30 participants), stroke or TIA (26 participants), hypertension (27 participants), grip strength (169 participants), premorbid IQ (90 participants), lifetime cognitive activity (38 participants), and current cognitive activity (43 participants). Score ranges are as follows: Barthel Index (0-20, scores ≥15 indicating independence in ADL), lifetime and current cognitive activity (score range 0-100 and 0-25, respectively; higher scores indicate more frequent cognitive activity), Thal phase (score range 0-5), Braak stage (score range 0-6), and CERAD score (score range 0-3) (higher scores indicate higher levels of pathology for these 3 measures).
Significant after correction for multiple testing (listed P values are uncorrected for multiple comparisons).