Predicting Alzheimer’s dementia in older people

A new study indicates that the severity of amyloid deposits in the brain, not just age, may be key in determining who will benefit from new anti-amyloid treatments aimed at delaying the progression of Alzheimer’s disease.

Clinicians and scientists at the University of Pittsburgh report that the accumulation of toxic beta-amyloid clumps that signal Alzheimer’s disease pathology accelerates with old age, but baseline amyloid load and overall health of the brain involved in this acceleration are more powerful predictors of who is more likely to progress. to Alzheimer’s disease. The article is published today in Neurology.

“Understanding the complexity of increased amyloid accumulation, when individuals are cognitively normal, is critical to improving the implementation of dementia treatments,” said corresponding author Oscar Lopez, MD, professor of neurology at Pitt and chief of cognitive and behavioral neurology at UPMC.

The overall presence, quantity and distribution of beta-amyloid, or A-beta, clusters in the brain are among the most common neuropathologies associated with Alzheimer’s disease. Yet, while people aged 80 and older have the highest prevalence of dementia associated with Alzheimer’s disease, most studies measuring A-beta load in the brain using drastic techniques Imaging has focused on younger populations. As such, the link between A-beta and dementia in older adults remains unclear.

Lopez and colleagues set out to change that by examining the relationship between A-beta deposits and new cases of dementia in 94 older adults who were not cognitively impaired when the study began. Participants were enrolled in the study at a mean age of 85 and followed for 11 years or until death, receiving at least two PET scans during the study. The rate of amyloid deposition in the brains of these individuals was compared to that of a younger group from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study.

The researchers observed a steady increase in A-beta accumulation in all participants over time, regardless of their A-beta status at the start of the study. But this accumulation was significantly faster in patients aged 80 and over than in participants in their late 60s, explaining the higher prevalence of A-beta in the oldest.

Ultimately, very few participants developed dementia without having 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 whose amyloid was negative.

The researchers also found that short-term change in beta alone over a 1.8-year period could not predict future dementia risk. In contrast, the severity of the initial A-beta load, as well as other markers of brain damage defined by the presence of white matter damage (a marker of small vessel disease) and a decrease in thickness gray matter in the cerebral cortex (a marker of neurodegeneration) were the strongest risk predictors, indicating that an active disease process was already in place at the start of the study.

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

Other 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 of Pitt.