Accelerated Temporal Cortex Tau Accumulation Mediates the Effects of Low Physical Activity on Faster Cognitive Decline in Preclinical Alzheimer’s Disease
Bibliographic record
Abstract
Abstract Background Physically inactivity is associated with increased risk of dementia including Alzheimer’s disease (AD). Prior work from the Harvard Aging Brain Study (HABS) suggests that lower baseline physical activity in cognitively unimpaired individuals with elevated amyloid burden is associated with faster prospective cognitive decline. However, whether this detrimental effect on cognition in preclinical AD is mediated by accelerated tau pathology remains unclear. Method We examined 293 baseline cognitively unimpaired older adults from HABS (Table 1). Baseline physical activity (mean steps per day) was measured using a waistband‐mounted pedometer (HJ‐720ITC; Omron Healthcare) worn over 7 consecutive days during waking hours. Using linear mixed effects models, we examined the interactive effects of baseline physical activity and amyloid PET burden (Pittsburgh Compound‐B) on longitudinal cognitive decline (Preclinical Alzheimer Cognitive Composite‐5 [PACC5]), adjusting for age, sex and education (APOE not significant). In a subset of 169 participants, we examined the interactive effects on longitudinal tau pathology (Flortaucipir PET) in 36 whole‐brain FreeSurfer cortical and limbic ROIs (FDR‐correction). We further investigated if the physical activity effects on PACC5 decline in preclinical AD are mediated by changes in tau. Result In a larger sample of HABS participants with up to 13 years of cognitive follow‐up, we replicated the significant interaction between lower physical activity and elevated amyloid burden on faster prospective cognitive decline (β = 0.09, t = 3.42, p<0.001; Figure 1A). We further demonstrated a novel interactive effect on tau pathology, where lower physical activity was associated with accelerated amyloid‐related tau accumulation in inferior temporal (ITC) and middle temporal (MTC) cortices (ITC: β = ‐0.10, t = ‐3.36, FDR‐p = 0.02; MTC: β = ‐0.09, t = ‐3.27, FDR‐p = 0.02; Figure 1B). Importantly, moderated mediation analyses revealed that accelerated tau accumulation fully mediated the effects of lower physical activity on faster cognitive decline in the setting of elevated amyloid (p<0.001, 100% mediated; Figure 2). Conclusion Our findings provide strong support for promoting physical activity as a lifestyle intervention, in conjunction with anti‐amyloid therapy, to slow the onset and/or progression of early neocortical tau pathology and cognitive decline in preclinical AD.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".