Table 1.
Longitudinal studies of the association between CR and AD biomarkers among individuals with normal cognition at baseline
| Study | Outcome Variable(s) |
AD-Biomarkers | CR measures | Mean clinical follow-up time in years (SD) |
Number of cognitively normal subjects at baseline |
Baseline CR- biomarker association |
CR associated with delayed clinical progression/ better cognitive performance accounting for baseline biomarker levels |
Longitudinal CR- biomarker association |
Relationship between biomarker and clinical/cognitive outcome modified by CR |
|---|---|---|---|---|---|---|---|---|---|
| Soldan, et al. (submitted) | Change in cognitive composite z-score | Composite z-score (CSF Aβ1–42, p-tau, entorhinal cortex thickness, hippocampal volume, cortical thickness in ADvulnerable regions) | Composite score (education, NART-IQ, WAIS-R vocabulary) | 12.1 (4.2) max=20 | 303 with clinical/cognitive data; 170 with baseline biomarker data | No | Yes, better baseline cognitive performance and faster decline after MCI symptom onset | – | No. |
| Pettigrew et al. (2017) | Time to onset of clinical symptom of MCI | Cortical thickness in AD vulnerable regions | Composite score (education, NART-IQ, WAIS-R vocabulary) | 11.8 (3.6) max=20 | 232 48 progressed |
No | Yes Delayed clinical progression | – | Yes, for those who progressed 7+ years after baseline only. |
| Soldan et al. (2015) | Time to onset of clinical symptom of MCI; Change in AD biomarkers | Volumes of hippocampus, entorhinal cortex, amygdala; entorhinal cortex thickness | Composite score (education, NART-IQ, WAIS-R vocabulary) | 11.1 (3.6), max=18 | 245 57 progressed |
No | Yes Delayed clinical progression | No | Yes, for left entorhinal cortex volume only. |
| Vemuri et al. (2015) | Change in cognitive composite z-score | Cortical PiB-PET (dichotomous); white matter hyperintensity volume, brain infarcts on FLAIR-MRI (dichotomous) | Education/occup ation score and self reported mid/late-life cognitive activity score | 2.7 | 393 | No | Yes, better baseline cognitive performance, but no difference in slope | – | No. |
| Soldan et al. (2013) | Time to onset of clinical symptom of MCI; Change in AD biomarkers | CSF Aβ1–42, t-tau, p-tau | Composite score (education, NART-IQ, WAIS-R vocabulary) | 8.0 (3.4), max=17 | 239 53 progressed |
No | Yes Delayed clinical progression | No | Yes, for CSF t-tau and p-tau. |
| Suo et al. (2012) | Change in hippocampal volume | Hippocampal volume, whole-brain volume (VBM) | Lifetime Experiences Questionnaire (LEQ) | 2–3 max = 3 | 151 | Yes, midlife LEQ/occupational complexity and bilateral hippocampus, and left amygdala | – | Yes, high supervisory experiences associated with less hippocampal atrophy (N=91) |
– |
| Lo & Jagust (2013) | Change AD biomarkers | CSF Aβ1-42, t-tau, p-tau, FDG-PET metabolism in 5 AD-vulnerable regions, hippocampal volume | Education (tertiles), occupation (3 levels), NART errors (tertiles) | 2–3, max = 3 | 229; 35 (CSF) 103 (FDG) 228 (HCV) |
No | – | Yes, higher CR associated with less decline in CSF Aβ1–42. | – |
| Roe et al. (2011a) | Time to CDR>=0.5; Change in CDR-SB, Short Blessed Test, MMSE | CSF Aβ1-42, t-tau, p-tau | Education | 3.3 (2.0) | 197 26 progressed |
– | Yes, delayed clinical progression after accounting for Aβ1-42, but not sig. among those with low tau/p-tau; Sig. among those with high tau/p-tau | – | Yes, among those with high tau or p-tau and low education, WBV was associated with faster progression. In low tau/p-tau group, neither education nor WBV associated with progression. Similar results obtained for CDR-SB and Blessed Test, but not for MMSE. |
| Roe et al. (2011b) | Time to CDR >=0.5 | CSF Aβ1-42, t-tau, p-tau | Education, occupational attainment (6 levels) | 3.2 (1.6) | 213 14 progressed |
– | Yes Delayed Clinical Progression | – | – |