Table 1.
Participant characteristics in the total sample, and by cognitive groups
| Characteristics | Total sample (n = 45) | MCI (n = 25) | CN (n = 20) | pa |
|---|---|---|---|---|
| Age at first cognitive assessment, Mean (SD), y | 69.8 (5.5) | 69.6 (5.3) | 70.0 (5.8) | 0.81 |
| Sex, n (%) | 0.77 | |||
| Male | 23 (51.1) | 12 (48.0) | 11 (55.0) | |
| Female | 22 (48.9) | 13 (52.0) | 9 (45.0) | |
| Self-reported race/ethnicity, n (%) | 0.53 | |||
| Non-Hispanic White | 39 (86.7) | 23 (92.0) | 16 (80.0) | |
| Black | 3 (6.7) | 1 (4.0) | 2 (10.0) | |
| Asian | 3 (6.7) | 1 (4.0) | 2 (10.0) | |
| Education, n (%) | >0.99 | |||
| College or lower | 17 (37.8) | 9 (36.0) | 8 (40.0) | |
| Post-college | 28 (62.2) | 16 (64.0) | 12 (60.0) | |
| BMI at first cognitive assessment, Mean (SD), kg/m2 | 27.3 (5.8) | 24.9 (3.6) | 30.4 (6.5) | 0.001 |
| Total physical activity,b median (IQR), MET-h/week | 21.7 (9.7 − 54.2) | 22.1 (6.9 − 61.1) | 18.5 (12.4 − 36.7) | 0.78 |
| Cigarette smoking, n (%) | >0.99 | |||
| Never | 25 (55.6) | 14 (56.0) | 11 (55.0) | |
| Past or current | 20 (44.4) | 11 (44.0) | 9 (45.0) | |
| Daily alcohol use, n (%) | >0.99 | |||
| Daily | 15 (34.1) | 8 (33.3) | 7 (35.0) | |
| Other than daily | 29 (65.9) | 16 (66.7) | 13 (65.0) | |
| Charlson-Deyo comorbidity index,c n (%) | >0.99 | |||
| 0 point | 40 (88.9) | 22 (88.0) | 18 (90.0) | |
| 1 + points | 5 (11.1) | 3 (12.0) | 2 (10.0) | |
| Estimated blood cell types,d mean (SD) | ||||
| Naїve CD8 + T cells | 175.1 (38.1) | 163.8 (31.5) | 189.3 (41.7) | 0.06 |
| Cytotoxic CD8 + T cellse | 5.9 (3.1) | 6.1 (2.9) | 5.6 (3.5) | 0.26 |
| CD4 + T cells | 0.2 (0.1) | 0.2 (0.1) | 0.2 (0.1) | 0.36 |
| Plasma blasts | 1.7 (0.2) | 1.7 (0.2) | 1.6 (0.2) | 0.04 |
| Natural killer cells | 0.0 (0.0) | 0.0 (0.0) | 0.0 (0.1) | 0.25 |
| Monocytes | 0.1 (0.0) | 0.1 (0.0) | 0.1 (0.0) | 0.26 |
| Granulocytes | 0.5 (0.1) | 0.6 (0.1) | 0.5 (0.1) | 0.04 |
| Second-generation DNAm markers, mean (SD) | ||||
| DNAmPhenoAgef , y | 55.8 (6.2) | 55.7 (6.3) | 55.9 (6.2) | 0.79 |
| AgeAccelPhenof , y | 0.2 (5.0) | 0.2 (5.2) | 0.2 (4.9) | 0.88 |
| DNAmGrimAgeg, y | 69.7 (5.1) | 69.5 (5.2) | 69.8 (5.0) | 0.69 |
| AgeAccelGrimg, y | 0.3 (2.9) | 0.3 (2.9) | 0.3 (2.9) | 0.86 |
| DNAmTLh , per 100-base pairs | 68.0 (2.4) | 68.0 (2.7) | 68.1 (2.0) | 0.92 |
| DNAmTLadjAgeh, per 100-base pairs | 0.0 (2.0) | −0.1 (2.4) | 0.1 (1.4) | 0.81 |
| Cognitive scores, mean (SD), standard units | ||||
| Global cognition scorei | −0.2 (0.8) | −0.7 (0.6) | 0.4 (0.5) | <0.001 |
| General cognition (3MS) score | 94.2 (5.0) | 92.2 (5.6) | 96.7 (2.7) | 0.005 |
| Verbal memory scorej | −0.1 (0.8) | −0.5 (0.6) | 0.5 (0.5) | <0.001 |
| Executive function/attention scorek | −0.2 (0.9) | −0.7 (0.9) | 0.3 (0.7) | <0.001 |
| Neuropsychiatric measures/scores, median (range) | ||||
| PHQ-9 score | 1.0 (0.0−4.0) | 1.0 (0.0 − 4.0) | 0.5 (0.0 − 4.0) | 0.97 |
| GAD-7 score | 0.0 (0.0 − 6.0) | 0.0 (0.0 − 6.0) | 0.5 (0.0 − 3.0) | 0.73 |
| NPI severity score | 1.0 (0.0 − 5.0) | 1.0 (0.0 − 5.0) | 1.0 (0.0 − 4.0) | 0.63 |
| Presence of NPS (≥2 NPI severity score) | 0.52 | |||
| Yes | 13 (28.9) | 6 (24.0) | 7 (35.0) | |
| No | 32 (71.1) | 19 (76.0) | 13 (65.0) |
CN, cognitively normal; MCI, mild cognitive impairment; DNAm, DNA methylation; SD, standard deviation; IQR, interquartile range; BMI, body mass index; MET, metabolic equivalent of task; 3MS, the modified mini-mental state; PHQ, patient health questionnaire; GAD, generalized anxiety disorder; NPS, neuropsychiatric symptoms; NPI, neuropsychiatric inventory.
For comparisons, we used the Wilcoxon-rank sum test for continuous variables and Fisher exact test for categorical variables.
Leisure-time physical activities include walking or hiking; jogging; running; bicycling; aerobic exercise/aerobic dance/exercise machines; lower intensity exercise/yoga/stretching/toning; tennis/squash/racquetball; lap swimming; weightlifting/strength training; other exercise.
The Charlson-Deyo comorbidity index is a weighted comorbidity score derived from the sum of the scores for each of several major medical comorbid conditions; participants were categorized as having 0 and 1 or more points [41, 42].
These are ordinal abundance measures of cell counts estimated in the Epigenetic clock by Horvath and colleagues. The abundance of I CD8 + T cells, exhausted CD8 + T cells, and plasma blasts were derived using the Horvath method [39]. The natural killer cells, monocytes, and granulocytes were derived using the Houseman method [40].
Exhausted CD8 + T cells were defined as CD8 positive CD28 negative CD45 R negative [39].
DNAmPhenoAge is a validated novel epigenetic clock that predicts varying aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer’s disease [4]. AgeAccelPheno is an age-accelerated residual measure of DNAmPhenoAge, derived by regressing epigenetic age on chronological age.
DNAmGrimAge is a validated novel DNAm biomarker which predicts lifespan and all-cause mortality [5]. AgeAccelGrim is an age-accelerated residual measure of DNAmGrimAge, derived by regressing epigenetic age on chronological age.
DNAmTL is a DNA methylation measurement of telomere length (unit is per 100-base pairs) [6]. DNAmTLadjAge is an age-accelerated residual measure of DNAmTL, derived by regressing epigenetic age on chronological aIe.
Global cognition score is a composite score for the mean of the z-scores of all cognitive tests.
Verbal memory score is a composite score for the mean of the z-scores of 4 tests: the immediate and delayed recalls of both the 10-word list and the East Boston Memory Test.
Executive function/attention score is a composite score for the mean of the z-scores of 4 tests: trails making tests A and B, and category fluency tests (naming animals and vegetables).