Advancing age is typically associated with declining memory capacity and increased risk of Alzheimer’s disease (AD). Markers of AD such as amyloid plaques (AP) and neurofibrillary tangles (NFTs) are commonly found in the brains of cognitively average elderly but in more limited distribution than in those at the mild cognitive impairment and dementia stages of AD. Cognitive SuperAgers are individuals over age 80 who show superior memory capacity, at a level consistent with individuals 20–30 years their junior. Using a stereological approach, the current study quantitated the presence of AD markers in the memory-associated entorhinal cortex (ERC) of seven SuperAgers compared with six age-matched cognitively average normal control individuals. Amyloid plaques and NFTs were visualized using Thioflavin-S histofluorescence, 6E10, and PHF-1 immunohistochemistry. Unbiased stereological analysis revealed significantly more NFTs in ERC in cognitively average normal controls compared with SuperAgers (P < 0.05) by a difference of ~3-fold. There were no significant differences in plaque density. To highlight relative magnitude, cases with typical amnestic dementia of AD showed nearly 100 times more entorhinal NFTs than SuperAgers. The results suggest that resistance to age-related neurofibrillary degeneration in the ERC may be one factor contributing to preserved memory in SuperAgers.

Objective: Older adults with exceptional memory function, designated “SuperAgers,” include individuals over age 80, with episodic memory at least as good as individuals ages 50s–60s. The Northwestern University SuperAging cohort is defined by performance on an established test of verbal memory. The purpose of this study was to determine if superior verbal memory extends to nonverbal memory in SuperAgers by examining differences in the National Institutes of Health Toolbox® (NIHTB) between older adults with exceptional memory and those with average-for-age cognition. Method: SuperAgers (n = 46) and cognitively average-for-age older adults (n = 31) completed a comprehensive neuropsychological battery and the NIHTB Cognition module. Multiple linear regressions were used to examine differences on subtests between groups. Results: There was a significant effect of group on the Picture Sequence Memory score, (p = .007), such that SuperAgers had higher scores than cognitively average-for-age older adults. There were no other group effects across other non-episodic memory NIHTB Cognition measures. Conclusions: Findings from this study demonstrated stronger performance on the memory measure of the NIHTB in SuperAgers compared to cognitively average-for-age older adults demonstrating superior memory in not only verbal but also nonverbal episodic memory in this group. Additionally, this study adds to the literature validating the NIHTB in older adults, particularly in a novel population of adults over age 80 with exceptional memory.

Background Memory complaints are widespread among the elderly and aging is a major risk factor for Alzheimer’s disease (AD), leading to the impression that gradual loss of memory ability is a nearly universal consequence of getting old. Our longitudinal studies of SuperAgers, 80+ year‐olds with episodic memory performance that remains in the range that is at least normal for 50‐60 year‐olds suggests an alternative aging trajectory is possible. This session will highlight some of the emerging biologic features of the SuperAgers. Method Participants include SuperAgers and cognitively average 80+ year‐old cognitively average normal controls. Data from detailed neuropsychological assessments, quantitative neuroimaging measurements (MR and amyloid PET), genetic features and neuropathologic findings will be reported. Result Initial evidence suggest SuperAgers tend to show mismatch between chronologic and biologic age, including maintenance of cortical but not necessarily hippocampal volume, a tendency to resist significant amyloid PET retention, an abundance of anterior cingulate Von Economo neurons, and some with resistance to cortical Alzheimer’s pathology. Conclusion These studies contribute to our understanding mechanisms of resilience and resistance in cognitive aging and may help isolate factors that are potentially important for promoting successful cognitive aging and avoiding age‐related brain diseases such as AD.

No abstract

Background Interest in factors contributing to superior cognitive aging has increased in recent years with the study of “SuperAgers” – individuals over age 80 with episodic memory performance similar to average middle‐aged adults. Given hippocampal involvement in memory formation, this project aimed to assess the integrity of this structure in the context of “SuperAging.” Method Participants included 67 SuperAgers (SA), 28 cognitively average 80+ year‐old cognitively average normal controls (O‐NC) and 25 middle‐aged cognitively average controls (MA‐NC). SA were age >80 with memory performance at or above normative values for individuals 50‐60 years of age and other cognitive scores normal for age. Control groups scored within the average range for age and education on all cognitive domains. Volume and shape of bilateral hippocampi in each participant was estimated using high‐dimensional surface mapping. Comparisons between groups included the use of repeated measure GLM designs. Result No significant effect for hippocampal volume by group (SA: left=2006.33, right=2550.02; O‐NC: left=2017.25, right=2537.94; MA‐NC: left=2208.98, right=2589.70; F 117,2=1.453 p=0.23), but a significant hemispheric effect (Right>Left; F 117,1=632.40, p<0.001) and group x hemisphere effect (F 117,2=6.65, p=0.002). Shape models revealed a significant difference among groups in left (F 216,20=9.23, p<0.001) and right (F 216,20=1.81, p=0.02) hippocampal shape. Follow‐up ANOVAs revealed this effect was primarily driven by MA‐NC shape differences (SA vs MA‐NC Left: F 81,10=16.71, p<0.001; Right: F 81,10=3.26, p=0.001). Hippocampal shape did not differ between SA and O‐NC (Left: F 93,10=0.95, p=0.5; Right: F 93,10=1.10, p=0.41), but did significantly differ between O‐NC and MA‐NC in the left hemisphere (F 42,10=12.02, p<0.001), but not the right hemisphere (F 42,10=1.10, p=0.42). Conclusion Despite exceptional episodic memory performance, hippocampal integrity does not appear to be a strong discriminating factor in older adults with superior memory function. While no differences in global hippocampal volume between groups emerged, significant shape differences were noted in both SuperAgers and their age similar controls relative to middle‐aged controls. Overall, our findings may represent a phenomenon where memory ability in old age serves more as a function of a diffuse network of cortical structures rather than a single region. Future exploration would include evaluating connectivity of hippocampal‐involved networks that include regions such as medial temporal cortical and diencephalic structures.