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Can one PET scan predict your cognitive future? Insights from a new study of older adults

Alongitudinal study of older adults has shown that individuals with higher concentrations of amyloid beta proteins in their brains experienced accelerated cognitive decline. This finding suggests that a single positron emission tomography (PET) scan assessing amyloid beta protein levels in the brain could be sufficient to predict the rate of cognitive decline in individuals. The study was published in the journal NeuroImage: Clinical. 

Amyloid beta (Aβ) plaques are protein deposits that accumulate in the brains of individuals with Alzheimer’s disease and, to a lesser extent, in several other types of age-related dementias. These plaques consist of densely packed fibers of amyloid beta, a protein normally produced and soluble in the brain. In Alzheimer’s disease and related conditions, this protein misfolds and aggregates into plaques, disrupting cell function and leading to neuron death in affected areas, which ultimately results in cognitive decline.  

The precise role of amyloid beta plaques in Alzheimer’s development is still under investigation. Some researchers believe these plaques initiate a series of neurodegenerative events, including inflammation and the formation of neurofibrillary tangles, another pathological marker. 

Research also indicates that Alzheimer’s disease has a lengthy preclinical phase, lasting 10 to 20 years, during which there are no evident symptoms of cognitive decline. However, various pathological changes, such as the accumulation of amyloid beta and another protein called tau, gradually occur in the brain. These changes disrupt the structure of brain neurons, and cognitive decline becomes apparent only after these accumulations reach substantial levels. 

In their new study, Gengsheng Chen and her colleagues aimed to determine whether a single measurement of amyloid beta protein levels in the brain can more accurately predict cognitive decline compared to tracking changes in this protein over time. They examined the relationship between cognitive ability indicators and amyloid beta protein levels in the brain.

The data for this study were collected from 153 older adults participating in longitudinal memory and aging studies at the Knight Alzheimer Disease Research Center at Washington University in St. Louis. The participants’ average age was 70 years, 57% were female, and 34% carried a genetic variant known to increase Alzheimer’s disease risk (APOE ε4 carriers). The average follow-up period was six years.

Throughout the study, participants underwent clinical dementia assessments, completed a battery of 10 different neurocognitive tests, and received positron emission tomography scans. Each participant included in the study had at least two assessments and two PET scans over the study period.

Positron emission tomography, or PET, is an imaging technique that uses radioactive substances, known as tracers, to visualize and measure metabolic processes in the body. This provides insights into organ and tissue function. The researchers used a tracer called Pittsburgh Compound B, which binds specifically to amyloid-beta plaques, allowing for the identification and quantification of these plaques in the brain.

The results revealed that individuals with higher amyloid beta protein concentrations in the brain at the study’s start experienced more rapid cognitive decline as the study progressed. However, changes in amyloid beta concentrations measured through multiple PET scans did not correlate with the rate of cognitive decline.

Overall, males, older individuals, and those with less education tended to have lower cognitive abilities at the beginning of the study. The sex of participants did not influence the relationship between amyloid beta concentrations and the rate of cognitive decline. Individuals carrying the APOE ε4 allele, associated with a higher risk of Alzheimer’s disease, exhibited faster cognitive decline.

Further analysis indicated that individuals with very low and very high initial levels of amyloid plaque had slower rates of plaque accumulation, while those with medium concentrations at the start tended to experience faster accumulation rates.

“The current study provides evidence that baseline Aβ [amyloid beta concentration] is more accurate than longitudinal Aβ for predicting cognition decline. Importantly, this study also confirms that covariates, such as the presence of the APOE ε4 allele, have deleterious group level effects on the ability of longitudinal Aβ measures to predict cognitive decline. From a clinical point of view, these results are encouraging as they provide evidence that only one amyloid positive PET scan is necessary in order to make predictions about future cognitive decline in individuals at risk for developing AD [Alzheimer’s disease],” the study authors concluded.

The study sheds light on the links between amyloid beta accumulation and cognitive decline. However, the design of the study does not allow any cause-and-effect conclusions to be drawn from the data. Therefore, it remains unclear whether the accumulation of amyloid beta plaque leads to cognitive decline or there is another factor or group of factors responsible both for cognitive decline and abnormal protein accumulation.

The paper, “Predicting cognitive decline: Which is more useful, baseline amyloid levels or longitudinal change?”, was authored by Gengsheng Chen, Nicole S. McKay, Brian A. Gordon, Jingxia Liu, Nelly Joseph-Mathurin, Suzanne E. Schindler, Jason Hassenstab, Andrew J. Aschenbrenner, Qing Wang, Stephanie A. Schultz, Yi Su, Pamela J LaMontagne, Sarah J. Keefe, Parinaz Massoumzadeh, Carlos Cruchaga, Chengjie Xiong, John C. Morris, and Tammie L.S. Benzinger. 

Reference: PSY Post