Home Medizin Eine erhöhte Anreicherung von β-Amyloid könnte bei älteren Menschen mit dem Risiko einer Alzheimer-Demenz verbunden sein

Eine erhöhte Anreicherung von β-Amyloid könnte bei älteren Menschen mit dem Risiko einer Alzheimer-Demenz verbunden sein

von NFI Redaktion

A new study suggests that the severity of amyloid accumulation in the brain, not just age, could be crucial in determining who will benefit from new anti-amyloid therapies to delay the progression of Alzheimer’s disease.

Clinicians and scientists at the University of Pittsburgh report that the accumulation of toxic amyloid beta clumps, which indicate the pathology of Alzheimer’s disease, accelerates with age, but the baseline burden of amyloid and overall brain health associated with this acceleration are more meaningful predictors of who is most likely to progress to Alzheimer’s. The paper was published today in Neurology, the medical journal of the American Academy of Neurology.

Understanding the complexity of increased amyloid accumulation in cognitively normal individuals is crucial for improved dementia treatments.“


Oscar Lopez, MD, corresponding author, Professor of Neurology at Pitt, and Head of Cognitive and Behavioral Neurology at UPMC

The presence as well as the total amount and distribution of amyloid beta or A-Beta clumps in the brain are among the most common neuropathologies associated with Alzheimer’s. However, while people aged 80 and older have the highest prevalence of Alzheimer’s-related dementias, most studies that measured A-Beta burden in the brain using imaging techniques focused on younger populations. Therefore, the association between A-Beta and dementia in the elderly remained unclear.

Lopez and his colleagues wanted to change that by examining the association between A-Beta deposits and new cases of dementia in 94 older adults who were cognitively unimpaired at the start of the study. The participants were enrolled at an average age of 85 years and followed for 11 years or until their death, receiving at least two PET scans during the study. The rate of amyloid accumulation in their brains was compared to a younger group from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study.

Over time, the researchers observed a steady increase in A-Beta accumulation in all participants, regardless of their A-Beta status at the start of the study. However, this accumulation was markedly faster in patients in their 80s and older compared to participants in their late 60s, which explains the higher prevalence of A-Beta in the elderly.

Finally, very few participants developed dementia without A-Beta deposits in the brain. Importantly, individuals whose brain scans were positive for amyloid at the start of the study developed dementia two years earlier than those who were amyloid-negative.

The researchers also found that the short-term change in A-Beta value alone over a period of 1.8 years could not predict future dementia risk. In contrast, the severity of A-Beta burden at the start of the study, along with other markers of brain injury such as the presence of white matter lesions (a marker of small vessel disease) and a decrease in the thickness of gray matter in the brain’s cortex (a marker of neurodegeneration), were the strongest predictors of risk, indicating that an active pathological process was already underway at the start of the study.

„Our results are consistent with studies showing that it takes decades for amyloid accumulation to develop in the brain and that it occurs in conjunction with other brain diseases, particularly small vessel diseases,“ said Lopez, who also directs the Pitt’s Alzheimer’s Disease Research Center. „Whether there is a vascular process running parallel to A-Beta accumulation could not be examined in this study. However, understanding the timing of the appearance of these pathologies will be crucial for the implementation of future primary prevention therapies.“

Additional authors of this research include Victor Villemagne, MD, YueFang Chan, Ph.D., Anne Cohen, Ph.D., William Klunk, MD, Chester Mathis, Ph.D., Tharick Pascoal, MD, Milos Ikonomovic, MD, Beth Snitz, Ph.D., Brian Lopresti, Ph.D., Ilyas Kamboh, Ph.D., and Howard Aizenstein, MD, all from Pitt.

This study was supported by the National Institutes of Health, the National Center for Complementary and Integrative Health and the Office of Dietary Supplements (grant U01 AT000162) as well as the National Institute on Aging (grants P30 AG066468, P01 AG025204, and RF1 AG052525).

Source:

Journal Reference:

López, OL, et al. (2024). Association between β-amyloid accumulation and incident dementia in persons aged 80 years and over without dementia. Neurology. doi.org/10.1212/wnl.0000000000207920.

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