The structural MRI markers and cognitive decline in prodromal Alzheimer’s disease: a 2-year longitudinal study
Bibliographic record
Abstract
BACKGROUND: Being clinically diagnosed with a mild cognitive impairment (MCI) due to Alzheimer's disease (AD) is widely studied. Yet, the clinical and structural neuroimaging characteristics for prodromal AD, which are defined as A+T+MCI based on the AT (N) system are still highly desirable. This study evaluates the differences of the cognitive assessments and structural magnetic resonance imaging (MRI) between the early MCI (EMCI) and late MCI (LMCI) participants based on the AT (N) system. The potential clinical value of the structural MRI as a predictor of cognitive decline during follow-up in prodromal AD is further investigated. METHODS: A total of 406 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were chosen and dichotomized into EMCI and LMCI groups according to the Second Edition (Logical Memory II) Wechsler Memory Scale. Multiple markers' data was collected, including age, sex, years of education, ApoE4 status, cerebrospinal fluid (CSF) biomarkers, standardized uptake values ratios (SUVR) means of florbetapir-PET-AV45, cognitive measures, and structural MRI. We chose 197 A+T+MCI participants (prodromal AD) with positive biomarkers of Aβ plaques (labeled "A") and fibrillar tau (labeled "T"). We diagnosed Aβ plaques positive by the SUVR means of florbetapir-PET-AV45 (cut-off >1.1) and fibrillar tau positive by CSF phosphorylated-tau at threonine 181 (p-tau) (cut-off >23 pg/mL). The differences of cognitive assessments and regions of interest (ROIs) defined on the MRI template between EMCI and LMCI were compared. Furthermore, the potential clinical utility of the MRI as the predictor of cognitive decline in prodromal AD was evaluated by investigating the relationship between baseline MRI markers and cognition decline at the follow-up period, through a linear regression model. RESULTS: The LMCI participants had a significantly more amyloid burden and CSF levels of total t-tau than the EMCI participants. The LMCI participants scored a lower result than the EMCI group in the global cognition scales and subscales which included tests for memory, delayed recall memory, executive function, language, attention and visuospatial skills. The cognition levels declined faster in the LMCI participants during the 12- and 24-month follow-up. There were significant differences in ROIs on the structural MRI between the two groups, including a bilateral entorhinal, a bilateral hippocampus, a bilateral amygdala, a bilateral lateral ventricle and cingulate, a corpus callosum, and a left temporal. The thickness average of the left entorhinal, the left middle temporal, the left superior temporal, and the right isthmus cingulate was a main contributor to the decreased global cognition levels. The thickness average of the left superior temporal and bilateral entorhinal played a key role in the memory domain decline. The thickness average of the left middle temporal, and the right isthmus cingulate was significantly associated with an executive function decline. CONCLUSIONS: Based on the AT (N) system, surely, both the EMCI and LMCI diagnoses presented significant differences in multiple cognition domains. Signature ROIs from the structural MRI tests had correlated a cognitive decline, and could act as one potential predictive marker.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".