Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer's disease neuropathology.
Level 3 - non-randomized controlled study
Non-randomized clinicopathological cohort study modeling longitudinal cognitive trajectories against post-mortem neuropathological findings.
PubMed 32883971 · doi:10.1038/s41598-020-71305-2
What was done
Authors developed cognitive trajectories for patients with common co-pathologies (TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies) in the presence and absence of Alzheimer's disease neuropathology. Trajectories were modeled using a Bayesian hierarchical regression framework to evaluate effects on cognitive decline assessed by the Mini-Mental State Examination and the Clinical Dementia Rating scale sum of boxes.
What was found
TDP-43 proteinopathy and cerebral amyloid angiopathy were associated with cognitive impairment of similar magnitude to that associated with Alzheimer's disease neuropathology. Among individuals with a neuropathological diagnosis of Alzheimer's disease, 63% possessed TDP-43 proteinopathy or cerebral amyloid angiopathy severe enough to independently explain the majority of their cognitive impairment. The abstract does not report specific numeric effect estimates, confidence intervals, or test statistics beyond this proportion.
Why it matters
These findings suggest that many clinical Alzheimer's presentations represent mixed dementias, meaning single-target therapies addressing only Alzheimer's pathology may show limited clinical efficacy in patients with substantial co-morbid proteinopathies.
Limits
The abstract does not state the sample size (n), participant demographics, or cohort source. Neuropathology was assessed post-mortem, preventing real-time verification of when each pathology emerged relative to cognitive testing milestones.
Cited by
- supports Postmortem examinations show that around 70% of Alzheimer's disease cases have vascular pathology contributing to the disease.