PET Scan of Super-Agers Crowned SNMMI Image of the Year

Older individuals who retain sharper mental agility – individuals dubbed “super-agers” – are more resistant to the tau and amyloid proteins that are associated with age-related mental decline, according to new research.

Capturing PET images from these adults who have lower tau and amyloid levels led a group of German investigators to receive the Image of the Year award from the Society of Nuclear Medicine and Molecular Imaging during the 2020 virtual annual meeting.

According to a team led by Merle Hoenig, Ph.D., from the Research Center Juelich and University Hospital Cologne, images from the super-agers groups were noticeably different from other patients in their 80s who had normal or only mildly impaired cognition.

“The phenomenon of super-aging suggests that cognitively high-functioning individuals have extraordinary mechanisms that resist brain aging processes and neurodegeneration,” Hoenig said in a statement. “We know that tau pathology is more closely associated with cognitive decline than amyloid pathology.”

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Consequently, she added, it is this tau pathology resistance that allows these older adults to maintain an above-average cognition level as their reach advanced age.

To make this determination, Hoenig’s team enrolled 75 older adults from the Alzheimer’s Disease Neuroimaging Initaitive. They divided them into three groups – 25 super-agers, 25 normal-agers, and 25 individuals with mild cognitive impairment. The average age of all patients was roughly 85. The investigators also examined 18 control participants, all in their mid-60s, who had no amyloid build-up.

Figure: Tau (blue) and amyloid (orange) distribution patterns for super-agers, normal-agers and MCI patients, when compared to a group of younger, healthy, cognitively normal, amyloid-negative individuals. Brain projections are depicted at an uncorrected significance level of p < .0001. Color bars represent the respective t-statistic. Credit: Merle C. Hoenig, Institute for Neuroscience and Medicine II – Molecular Organization of the Brain, Research Center Juelich, Juelich, Germany, and Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany.

The team conducted PET scans with both ¹⁸F-AV-1451 and ¹⁸F-AV-45 to examine the differences in tau and amyloid collection among all the groups. Image analysis revealed no significant differences with in vivo tau and amyloid burden between the super-agers and the control group. However, those who were aging normally demonstrated tau burden in inferior temporal and precuneal areas, but no significant differences in amyloid burden in comparison to their younger cohorts. That amyloid burden difference did set them apart, though, from the mild cognitive impairment group who had high amyloid and high tau pathology burdens.

Based on these findings, Hoenig said, it is possible that super-agers have a resistance to these proteins that other individuals do not.

“Normal-agers may not [be able to resist tau pathology] and are, thus exposed to inevitable cognitive decline due to the accumulation of neurotoxic tau tangles and the advancing aging process,” she said. “Moving further to the other extreme of aging, namely mild cognitive impairment, the synergistic effects of both amyloid and tau may accelerate the pathological aging process.”

Additional research is needed, she said, to shed light on the many factors that could play into dementia resistance, potentially leading to effective treatments.

“Given the multitude of factors involved in the aging process, it will certainly be challenging to develop therapeutics to tackle the factors involved,” she explained. “However, if we understand which individuals are resistant to dementia, this will help us identify potential pathways that promote successful aging – protecting against not only Alzheimer’s disease but also other aging-associated diseases, such as vascular disease and other forms of dementia.”

Read more coverage of Society of Nuclear Medicine and Molecular Imaging 2020 here.