TABLE 1.
Baseline demographic and clinical characteristics of the study participants by cognitive impairment and dementia status
| All | Cognitively unimpaired (CU) | Mild cognitive impairment (MCI) | Dementia | CU vs. MCI a | MCI vs. dementia a | CU vs. dementia a | |
|---|---|---|---|---|---|---|---|
| Main cohort, N | 248 | 120 | 83 | 45 | |||
| Age (years, mean ± std), baseline | 75.3 ± 5.6 | 74.7 ± 5.4 | 75.8 ± 5.7 | 76.2 ± 5.8 |
t = 1.31 P = .19 |
t = 0.26 P = .79 |
t = 1.36 P = .175 |
| Sex (F %) | 51% | 59% | 41% | 47% | P = .016 | P = .71 | P = .16 |
| Education (years, mean ± std) | 16.4 ± 2.4 | 16.8 ± 2.1 | 16.1 ± 2.6 | 16.1 ± 2.4 |
t = ‐2.16 P = .032 |
t = 0.11 P = .91 |
t = ‐1.74 P = .084 |
| APOE ε4 (carrier, %) | 61% | 53% | 63% | 78% | P = .0057 | P = .17 | P < 10−4 |
| Aβ centiloid (mean ± std), baseline | 72.6 ± 37.7 | 60.0 ± 32.6 | 77.3 ± 38.0 | 97.4 ± 36.3 |
t = 3.48 P = .00063 |
t = 2.89 p = 0.0045 |
t = 6.31 p < 10−8 |
| WML (ICV %), baseline | 0.39 ± 0.69 | 0.29 ± 0.37 | 0.49 ± 1.04 | 0.46 ± 0.47 |
t = 1.98 P = .049 |
t = ‐0.23 P = .82 |
t = 2.36 P = .019 |
| ADAS–Cog (mean ± std), baseline | 19.1 ± 10.1 | 12.9 ± 4.8 | 19.9 ± 6.8 | 34.3 ± 9.0 |
t = 8.56 P < 10−14 |
t = 10.14 P < 10−16 |
t = 19.41 P < 10−16 |
| ADAS–Cog (mean ± std), rate of change | 1.53 ± 1.04 | 0.91 ± 0.48 | 1.79 ± 0.87 | 3.14 ± 0.92 |
t = 8.17 P < 10−12 |
t = 6.63 P < 10−8 |
t = 16.63 P < 10−16 |
| mPACC (mean ± std), baseline | −4.85 ± 7.20 | 0.02 ± 2.8 | −5.89 ± 4.34 | −15.9 ± 6.5 |
t = ‐11.59 P < 10−16 |
t = ‐10.27 P < 10−16 |
t = ‐21.45 P < 10−16 |
| mPACC (mean ± std), rate of change | −0.79 ± 1.02 | −0.11 ± 0.40 | −1.05 ± 0.69 | −2.50 ± 0.97 |
t = ‐10.54 P < 10−16 |
t = ‐8.02 P < 10−11 |
t = ‐18.37 P < 10−16 |
| CDR‐SB (mean ± std), baseline | 1.59 ± 2.42 | 0.09 ± 0.29 | 1.58 ± 1.21 | 5.6 ± 2.7 |
t = 12.95 P < 10−16 |
t = 11.46 P < 10−16 |
t = 21.66 P < 10−16 |
| MMSE (mean ± std), baseline | 27.0 ± 3.54 | 28.9 ± 1.3 | 27.3 ± 2.3 | 21.6 ± 3.9 |
t = ‐6.46 P < 10−9 |
t = ‐10.24 P < 10−16 |
t = ‐17.76 P < 10−16 |
| Logical memory – delayed (mean ± std), baseline | 9.09 ± 5.98 | 13.6 ± 3.5 | 6.69 ± 4.40 | 1.4 ± 2.7 |
t = ‐12.26 P < 10−16 |
t = ‐7.06 P < 10−9 |
t = ‐20.29 P < 10−16 |
| RAVLT – immediate (mean ± std), baseline | 37.4 ± 13.7 | 46.0 ± 11.0 | 33.1 ± 10.2 | 22.1 ± 7.7 |
t = ‐8.46 P < 10−14 |
t = ‐6.06 P < 10−7 |
t = ‐12.97 P < 10−16 |
| RAVLT – learning (mean ± std), baseline | 4.47 ± 2.86 | 6.0 ± 2.3 | 3.6 ± 2.8 | 2.0 ± 2.0 |
t = ‐6.52 P < 10−9 |
t = ‐3.32 P = .0012 |
t = ‐9.82 P < 10−16 |
| RAVLT – forgetting (mean ± std), baseline | 4.02 ± 3.98 | 3.8 ± 2.8 | 4.0 ± 5.8 | 4.7 ± 1.8 |
t = 0.54 P = .59 |
t = 0.79 P = .43 |
t = 2.32 P = .022 |
| Trail Making Test – B (mean ± std), baseline | 109.6 ± 73.2 | 77.7 ± 36.6 | 118.3 ± 71.1 | 191.6 ± 94.2 |
t = 5.25 P < 10−6 |
t = 4.85 P < 10−5 |
t = 11.00 P < 10−16 |
| Conversion to MCI within 4 years; N (%) | 14 (12%) | ||||||
| Conversion to dementia within 4 years; N (%) | 17 (20%) |
Notes: All study participants had PET imaging evidence for Aβ‐positivity b . The study cohort was limited to individuals of age ≥65 years and ≤85 years. Selection was made a priori from all ADNI subjects based on the availability of complete data including cross‐sectional neuroimaging, longitudinal clinical and cognitive measures, and APOE genotyping as of February 28, 2021. Because previous studies have shown that neuropathological features of dementia in the oldest‐old could differ from those of cognitively impaired younger‐old individuals, the study cohort was limited to individuals of age ≥65 years and ≤85 years. 56 Only one of the participants in this study cohort had autopsy findings, which confirmed AD neuropathologic changes of frequent neuritic plaques and neurofibrillary degeneration at Braak & Braak stage 5, and additionally identified regional TDP‐43 pathological inclusions, Lewy‐body pathology, and mild cerebral amyloid angiopathy.
Abbreviations: Aβ, amyloid beta; ADAS‐Cog, Alzheimer's Disease Assessment Scale–Cognitive subscale; ADNI, Alzheimer's Disease Neuroimaging Initiative; APOE, apolipoprotein E; CDR‐SB, Clinical Dementia Rating–Sum of Boxes; MMSE, Mini‐Mental State Examination; PACC, Preclinical Alzheimer Cognitive Composite; PET, positron emission tomography; RAVLT, Rey Auditory Verbal Learning Test; ROI region of interest; std, standard deviation; SUVR, standardized uptake value ratio; WML, white matter lesion.
Descriptive statistics for continuous variables were compared between groups with an independent‐samples t‐test, and categorical variables with the chi‐square test.
A composite ROI consisting of middle frontal, anterior cingulate, posterior cingulate, inferior parietal, precuneus, supramarginal, middle temporal, and superior temporal was used to compute a global SUVR for florbetapir and florbetaben. A threshold of SUVR ≥ 1.11 for florbetapir and ≥ 1.08 for florbetaben was then used to determine Aβ‐positivity status.