Association of the Informant-Reported Memory Decline With Cognitive and Brain Deterioration Through the Alzheimer Clinical Continuum
Bibliographic record
Abstract
Background and objectives: Studies are sparse regarding the association between the informant-reported subjective memory decline (informant-report) and Alzheimer’s disease (AD) biomarkers. This study thus aimed at determining the clinical relevance of the informant-report throughout the AD clinical continuum, by assessing its specific relationships with amyloid deposition, cognition and neurodegeneration. Methods: Participants from the Imagerie Multimodale de la maladie d9Alzheimer à un stade Précoce (IMAP+) primary cohort and from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) replication cohort were included; all underwent multimodal neuroimaging and neuropsychological assessments. Follow-up data of IMAP+ participants over up to 36 months were also used for longitudinal analyses. The informant-report was measured respectively with the Cognitive Difficulties Scale (IMAP+) and Everyday Cognition (ADNI). General linear models were used to assess the cross-sectional associations between the informant-report and amyloid-PET, cognitive performances, and neurodegeneration (atrophy and hypometabolism) in Alzheimer’s-signature areas; while longitudinal links were assessed in IMAP+ with linear mixed-effects models. Results: 110 IMAP+ participants were included, including 32 cognitively unimpaired elders (controls, age: 70.91±6.57, female:50%), 25 patients with subjective cognitive decline (SCD, 65.88±6.64, 40%), 35 with mild cognitive impairment (MCI, 72.49±7.5, 34%) and 18 with Alzheimer’s-type dementia (AD dementia, 68.17±8.59, 28%). 731 ADNI participants were included, including 157 controls (74.21±5.95, 55%), 84 SCD (72.00±5.41, 63%), 369 MCI (71.84±7.4, 44%) and 121 AD dementia (74.29±7.75, 40%). In IMAP+, higher informant-report strongly correlated to greater amyloid-PET specifically in MCI patients (β=0.48, p=.003), and to lower cognitive performance in SCD (global cognition, β=-0.41, p=.04) and MCI patients (memory, β=-0.37, p=.03). Findings in MCI patients were replicated in ADNI (amyloid-PET, β=0.25, p<.001; memory, β=-0.22, p<.001), and extended to neurodegeneration in AD signature areas (β=-0.2, p<.001). Longitudinal analyses in IMAP+ showed links with global cognitive decline over time in MCI (est. -0.74, SE 0.26, p=.005) and in SCD (est. -0.36, SE 0.26, p=.02) patients where higher baseline informant-report also predicted increased amyloid-PET over time (est. 0.008, SE 0.003, p=.02). Discussion: Altogether, our findings suggest that the informant-report is particularly relevant in MCI patients where it strongly relates to higher amyloid-PET, indicative of impairment due-to-AD. Trial registration information: ClinicalTrials.gov Identifier: NCT01638949
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".