F5‐05‐02: NEUROPSYCHIATRIC BURDEN IS RELATED TO INCREASED AMYLOID BUT NOT TAU DEPOSITION IN COGNITIVELY NORMAL OLDER ADULTS
Bibliographic record
Abstract
Neuropsychiatric factors (NPF; e.g. depression, anxiety, apathy) are highly prevalent in older adults and are associated with an increased risk of Alzheimer's disease (AD) (Masters et al, 2015). Recent evidence also linked personality traits (e.g. neuroticism) with progression to AD (Terracciano et al, 2017). The mechanisms by which personality/NPF burden influence AD risk need to be better understood. In cognitively normal older adults at risk of AD, we investigated whether an index of personality/NPF burden was related to AD pathology (amyloid [Aβ] and tau deposition), brain function and cognition. Eighty-two participants (PREVENT-AD study, age=67±5) answered questionnaires assessing personality, perseverative thinking, depression, anxiety, stress and apathy. They underwent Aβ-PET ([18F]NAV4694), tau-PET ([18F]AV1451), resting-state fMRI and cognitive assessment (Repeatable Battery for Assessment of Neuropsychological Status). PET SUVRs were extracted bilaterally from all FreeSurfer Desikan neocortical regions. We used a multivariate approach (partial least squares correlation with permutation tests) to assess which combination of factors was related to Aβ and tau deposition. We then investigated whether this index of personality/NPF burden was related to 1) functional connectivity and 2) cognitive performance in individuals with and without significant AD pathology. Aβ (p=0.003), but not tau (p>0.05) was related to personality/NPF burden. More specifically, a combination of perseverative thinking, neuroticism and apathy was associated with higher Aβ accumulation, predominantly in the AD-signature regions (Fig.1). Higher scores on this personality/NPF component were additionally associated with higher connectivity within the dorsal attention and salience networks in Aβ+ subjects, and lower connectivity in Aβ- subjects (Aβ-status*connectivity: F1,69=5.7-5.2, p=.02-.03 respectively, Fig.2A). Furthermore, higher scores on this personality/NPF component were associated with worse immediate memory (F1,70=4.1, p=.05, Fig.2B), regardless of Aβ status. Relative importance of personality traits and neuropsychiatrie factors (NPF) in relation to regional Aβ accumulation. IA. Loading of each personality traits and NPF score from the component relating personality/NPF with Aβ burden. Traits and factors contributing the most to the model are perseverative thinking, neuroticism and apathy. Confidence intervals are derived from bootstrap resampling. IB. Cortical regions showing higher Aβ SUVR as personality/NPF burden increases. The importance of each region in the model was identified from bootstrap ratios and projected on a brain template. Personality/NPF relationship with brain function (A) and cognition (B) 2A. Functional networks showing a significant interaction of Aβ status by functional connectivity on the personality/NPF burden. 2B. Relationship between personality/NPF burden and immediate memory performance. Our multivariate approach revealed that Aβ burden was increased in cognitively normal individuals at risk of AD showing high levels of perseverative thinking, neuroticism and apathy, which were in turn related to altered brain connectivity and lower cognition. Overall, these results highlight the importance of personality/NPF burden on early AD pathophysiology.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".