With this your competent? stroke medical 'professionals' should be able to create a dementia prevention protocol! But I bet they don't even try! What it means is your doctor has to have protocols to increase your cognitive reserve. I probably used up most of mine just surviving my stroke.
What the Brains of Centenarians Reveal
"Amyloid-beta pathology is not a benign consequence of aging," researchers maintain
Key Takeaways
- More than half of 95 centenarians had a low amyloid load and 9% had no amyloid, autopsy data showed.
- A third of centenarians had a high amyloid load comparable to Alzheimer's disease.
- Five centenarians maintained high cognitive performance despite a high amyloid load.
Most people who survived to age 100 and beyond had amyloid-beta accumulation and, when present, it was tied to cognitive performance, an autopsy study showed.
In a study of 95 centenarians, more than half (56%) had a low amyloid load and 9% had no amyloid load, according to Henne Holstege, PhD, of Vrije Universiteit Amsterdam, and colleagues.
One-third of centenarians (35%) had a high amyloid load comparable to Alzheimer's disease, the investigators reported in JAMA Neurology. Higher amyloid loads across four neocortical regions affected executive functioning.
Five centenarians maintained high cognitive performance despite having a high amyloid load, scoring in the top 25% on executive functioning or global cognition tests. These five people had significantly less tau pathology than centenarians with a high amyloid load and lower cognitive performance.
"These results indicate that amyloid-beta pathology is not a benign consequence of aging," Holstege and co-authors wrote. "Even in the oldest individuals, amyloid-beta and tau pathology interaction was consistent with the amyloid cascade hypothesis."
The study contributes to the growing evidence that "despite advanced age being a major risk factor for Alzheimer's disease, dementia is not inevitable with aging even to extreme ages," noted Stacy Andersen, PhD, of the New England Centenarian Study at Boston University, who wasn't involved with the research.
Some centenarians are resistant to Alzheimer's disease -- they don't have amyloid or tau buildup -- while others are resilient, meaning they can maintain good cognitive function even with amyloid pathology, she pointed out.
"This study suggests that a key to resilience among centenarians is that although amyloid and tau may be present, they are present at a lower, more manageable level that is less likely to cause cognitive impairment," Andersen told MedPage Today.
"Identifying these protective mechanisms that keep Alzheimer's-related proteins at bay in these exceptional people has the potential to lead to therapeutics to help all of us maintain good cognitive function until the end of life," she added.
Previous work by Holstege and colleagues showed that cognitive reserve and physical health factors were tied to cognitive performance in people who lived past 100 years.
The current study focused on amyloid loads and distribution patterns in 95 centenarians from the Dutch 100-plus study to see whether these factors correlated with cognitive outcomes close to death. Centenarians self-reported being cognitively healthy when they joined the study; this was confirmed by proxy.
The researchers determined quantitative loads in the frontal, parietal, temporal, and occipital neocortices, three parahippocampal, and five hippocampal subregions, and used the Thal phase system to assess amyloid progression. The Thal phase evaluates amyloid progression in five phases: neocortex (phase 1), allocortex (phase 2), diencephalon and striatum (phase 3), brainstem (phase 4), and cerebellum (phase 5). People with Alzheimer's typically have a Thal phase of 3 or higher.
The study used 13 individual tests to assess cognitive function and developed a composite global cognition score for 72 centenarians. Global cognition was evaluated for all 95 centenarians using the Mini-Mental State Examination. Cognitive performance was measured a median of 10 months before postmortem brain donation.
Centenarians were compared with 38 patients who had clinicopathologically confirmed Alzheimer's disease from the Netherlands Brain Bank. Centenarians had a median age of 103.5 years at brain donation; 75% were female. Alzheimer's patients had a median age of 84 at donation and 47% were female.
Only nine centenarians had a Thal phase of 0. In amyloid-positive centenarians -- those with a Thal phase of at least 1 -- the spatiotemporal distribution of cortical amyloid load was similar to Alzheimer's patients: amyloid load was highest and most frequent in the frontal cortex, followed by the parietal, temporal, and occipital cortices.
Levels of neurofibrillary tangles, TAR DNA-binding protein (TDP)-43 stage, and hippocampal sclerosis co-pathologies correlated with amyloid pathology and may have contributed to changes in cognitive performance, Holstege and colleagues noted.
The study did not assess specific amyloid isoforms that may influence cognitive performance, they observed. Future studies should address this as therapeutics like donanemab (Kisunla) target specific amyloid-beta isoforms, the researchers said.
Disclosures
This study was supported by BrightFocus, the VUMC Foundation, and Surf Sara.
Holstege was supported by ABOARD, a public-private partnership receiving funding from ZonMw and Health Holland, Topsector Life Sciences and Health, the Hans und Ilse Breuer Stiftung, the Horstingstuit Foundation, and the Dutch Research Council. Co-authors reported relationships with nonprofit groups and pharmaceutical companies.
Primary Source
JAMA Neurology
Source Reference: Rohde SK, et al "Amyloid-beta pathology and cognitive performance in centenarians" JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2025.1734.
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