Prevention of age-related cognitive decline is an increasingly important topic. Recently, increased attention is being directed at understanding biological models of successful cognitive aging. Here, we examined resting-state brain regional low-frequency oscillations using functional magnetic resonance imaging in 19 older adults with excellent cognitive abilities (Supernormals), 28 older adults with normative cognition, 57 older adults with amnestic mild cognitive impairment, and 26 with Alzheimers disease. We identified a Supernormal map, a set of regions whose oscillations were resistant to the aging-associated neurodegenerative process, including the right fusiform gyrus, right middle frontal gyrus, right anterior cingulate cortex, left middle temporal gyrus, left precentral gyrus, and left orbitofrontal cortex. The map was unique to the Supernormals, differentiated this group from cognitive average-ager comparisons, and predicted a 1-year change in global cognition (indexed by the Montreal Cognitive Assessment scores, adjusted R2 = 0.68). The map was also correlated to Alzheimers pathophysiological features (beta-amyloid/pTau ratio, adjusted R2 = 0.66) in participants with and without cognitive impairment. These findings in phenotypically successful cognitive agers suggest a divergent pattern of brain regions that may either reflect inherent neural integrity that contributes to Supernormals cognitive success, or alternatively indicate adaptive reorganization to the demands of aging.

Memory deterioration is the earliest and most devastating cognitive deficit in normal aging and Alzheimer's disease (AD). Some older adults, known as "Supernormals", maintain excellent memory. This study examined relationships between cerebral amyloid deposition and functional connectivity (FC) within the cingulate cortex (CC) and between CC and other regions involved in memory maintenance between Supernormals, healthy controls (HC), and those at risk for AD (amnestic mild cognitive impairment [MCI]). Supernormals had significantly stronger FC between anterior CC and R-hippocampus, middle CC (MCC) and L-superior temporal gyrus, and posterior CC (PCC) and R-precuneus, while weaker FC between MCC and R-middle frontal gyrus and MCC and R-thalamus than other groups. All of these FC were significantly related to memory and global cognition in all participants. Supernormals had less amyloid deposition than other groups. Relationships between global cognition and FC were stronger among amyloid positive participants. Relationships between memory and FC remained regardless of amyloid level. This revealed how CC-related neural function participates in cognitive maintenance in the presence of amyloid deposition, potentially explaining excellent cognitive function among Supernormals.

Studying older adults with excellent cognitive capacities (Supernormals) provides a unique opportunity for identifying factors related to cognitive success - a critical topic across lifespan. There is a limited understanding of Supernormals' neural substrates, especially whether any of them attends shaping and supporting superior cognitive function or confer resistance to age-related neurodegeneration such as Alzheimer's disease (AD). Here, applying a state-of-the-art diffusion imaging processing pipeline and finite mixture modelling, we longitudinally examine the structural connectome of Supernormals. We find a unique structural connectome, containing the connections between frontal, cingulate, parietal, temporal, and subcortical regions in the same hemisphere that remains stable over time in Supernormals, relatively to typical agers. The connectome significantly classifies positive vs. negative AD pathology at 72% accuracy in a new sample mixing Supernormals, typical agers, and AD risk [amnestic mild cognitive impairment (aMCI)] subjects. Among this connectome, the mean diffusivity of the connection between right isthmus cingulate cortex and right precuneus most robustly contributes to predicting AD pathology across samples. The mean diffusivity of this connection links negatively to global cognition in those Supernormals with positive AD pathology. But this relationship does not exist in typical agers or aMCI. Our data suggest the presence of a structural connectome supporting cognitive success. Cingulate to precuneus white matter integrity may be useful as a structural marker for monitoring neurodegeneration and may provide critical information for understanding how some older adults maintain or excel cognitively in light of significant AD pathology.