Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on cognitive decline: Minimal impact of vascular brain injury compared with other combinations.
Level 3 - non-randomized controlled study
Longitudinal clinicopathological cohort study evaluating post-mortem pathology and pre-mortem cognitive trajectories
PubMed 42024684 · doi:10.1093/jnen/nlag033
What was done
Researchers analyzed 808 participants from the National Alzheimer's Coordinating Center (NACC) database to determine how co-occurring neuropathologies modify cognitive decline in Alzheimer disease neuropathologic change (ADNC). Post-mortem neuropathologic assessments for ADNC, Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were linked to longitudinal neuropsychological trajectories across five domains (overall cognition, episodic memory, attention, language, and executive function). Linear mixed-effects models compared rates of decline for ADNC alone against combinations (ADNC+LBD, ADNC+LATE-NC, ADNC+VBI) and tested whether co-pathology effects were additive or subadditive.
What was found
The abstract reports directional domain counts rather than specific numerical effect sizes or p-values: - ADNC + LBD: Produced steeper cognitive decline than ADNC alone across 4 of the 5 cognitive domains; decline rates matched an additive model across all 4 domains. - ADNC + LATE-NC: Resulted in worse decline than ADNC alone across 3 domains, with rate of decline fitting an additive pattern for 1 domain and less-than-additive (<additive) for 2 domains. - ADNC + VBI: Showed worse decline than ADNC alone in only 1 cognitive domain, with a rate of decline that was less-than-additive.
Why it matters
These findings clarify how specific concurrent neuropathologies accelerate clinical decline, demonstrating that neurodegenerative co-pathologies (LBD and LATE-NC) contribute substantially more to progressive impairment in ADNC than vascular brain injury, which has implications for clinical trial stratification and patient prognostication.
Limits
Exact regression coefficients, standard errors, confidence intervals, and p-values are omitted from the abstract. The cohort consists of volunteer autopsy donors from specialized Alzheimer's centers, introducing potential referral and selection biases. Pathology is determined only at end-of-life autopsy, whereas cognitive trajectories reflect pre-mortem testing over variable and unspecified follow-up intervals.
Cited by
- contradicts Postmortem brain tissue from Alzheimer's disease patients consistently displays vascular pathology across every single case.