Youthful memory capacity in old brains: anatomic and genetic clues from the Northwestern SuperAging Project

Abstract

The Northwestern University SuperAging Project recruits community dwellers over the age of 80 who have unusually high performance on tests of episodic memory. In a previous report, a small cohort of SuperAgers was found to have higher cortical thickness on structural MRI than a group of age-matched but cognitively average peers. SuperAgers also displayed a patch of ACC where cortical thickness was higher than in 50- to 60-year-old younger cognitively healthy adults. In additional analyses, some SuperAgers had unusually low densities of age-related Alzheimer pathology and unusually high numbers of von Economo neurons in the anterior cingulate gyrus. SuperAgers were also found to have a lower frequency of the ɛ4 allele of apolipoprotein E than the general population. These preliminary results show that above-average memory capacity can be encountered in advanced age. They also offer clues to potential biological factors that may promote resistance to age-related involutional changes in the structure and function of the brain.

Figure 1

Increase in the magnitude of interindividual variation in memory performance over the life span. Gray shading reflects ±1SD from the mean and demonstrates the widening of the standard deviation over the life span due to higher interindividual variation in aging. Triangles represent elite performers who may be immune to the common age related declines in episodic memory. Circles represent individual data. Lines represent averages for 35–49, 50–59, 60–69, and 70–85 from left to right, respectively. Reprinted (with modifications) from McDaniel, Einstein, and Jacoby (2008).

Figure 2

Cortical thickness differences in average cognitive agers and cognitive SuperAgers. (A) Red and yellow regions show significant regional cortical thinning across both hemispheres in the cognitively average elderly controls compared with the cognitively average middle-age cohort. (B) There is no significant thinning in the SuperAging group in either hemisphere compared with middle-aged controls. A region within the ACC (blue) is significantly thicker in SuperAgers when compared with middle-aged controls. False discovery rate was set at 0.05. LH = left hemisphere; RH = right hemisphere. Reprinted (with modifications) from Harrison et al. (2012) with the permission of Cambridge University Press. Copyright© 2012 The International Neuropsychological Society.

Figure 3

Extremely sparse Alzheimer pathology in the anterior aspects of cingulate cortex (BA 24) in a 90-year-old SuperAger (Case 3). (A) Nissl-stained sections revealed high packing density of neurons in the anterior cingulate. Arrows in A point to von Economo neurons. Most of this cortical region was devoid of plaques or tangles. Only isolated phosphorylated tau-stained (B, PHF-1, less than one per section) or thioflavin-S-positive tangles (C, less than one per section) and amyloid-β-positive plaques (D, 6E10, two per section) were detected in this region. Scale bars: 1 mm (A) and 100 μm (D; also applies to B and C).

Figure 4

Coronal section of a T1-weighted MRI scan from a 90-year-old SuperAger (SuperAger 3 in Table 1) who came to autopsy. The cortical ribbon is largely preserved, and the hippocampus and the entorhinal cortex do not show any obvious atrophy.