Age-related brain protein changes linked to poorer cognition
The changes were linked to a 4.06-point higher dementia rating score, compared with 3.78 points for moderate or severe Alzheimer’s-related changes.
Our read
Populations- Studied:
- Cross-sectional study of 1,860 deceased people in Brazil
- What changed:
- Age-related brain protein changes were linked to a 4.06-point higher dementia rating score
- The catch:
- Only 0.4% had stage 3 changes, limiting precision for advanced-stage cases
- In the record:
- The 14th paper on limbic-predominant age-related TDP-43 encephalopathy neuropathologic change with results in people; 21 on record in all.
- Why it’s aging research:
- It measures an outcome that worsens with age.
Editor of record: Boris Djordjevic · AgingResearch.News
The brains of 1,860 people in Brazil, averaging 72.6 years old and 49.1% female, were examined in a cross-sectional autopsy study. The ethnoracially and socioeconomically diverse sample came from autopsies performed between 2004 and 2024. The team assessed age-related brain changes involving a protein called TDP-43, alongside other brain abnormalities. They evaluated cognitive abilities using a dementia rating scale.
The TDP-43-related changes appeared in 7.4% of participants. After accounting for sociodemographic and clinical factors and other brain abnormalities, these changes remained associated with cognitive impairment. The association was similar to that seen with moderate or severe Alzheimer’s-related brain changes.
Why it matters
Cognitive impairment in aging raises questions about overlapping brain conditions, including changes beyond those associated with Alzheimer’s disease.
Caveats
The cross-sectional analysis did not track how the brain changes and cognitive impairment developed over time. Some estimates were imprecise because few participants had advanced-stage changes.
- Cognitive impairment
- Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change
- Alzheimer's disease neuropathologic change
- Cerebral amyloid angiopathy
- Hippocampal sclerosis
- Humans
The paper
University of São Paulo Medical School
Neurology, Nov 5, 2026
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