Morphometric and Histologic Substrates of Cingulate Integrity in Elders with Exceptional Memory Capacity

• Published in: The Journal of neuroscience Vol. 35; no. 4; pp. 1781 - 1791
• Main Authors: Gefen, Tamar, Peterson, Melanie, Papastefan, Steven T., Martersteck, Adam, Whitney, Kristen, Rademaker, Alfred, Bigio, Eileen H., Weintraub, Sandra, Rogalski, Emily, Mesulam, M.-Marsel, Geula, Changiz
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 28.01.2015
• Subjects: Aged; Aged, 80 and over; Aging; Alzheimer Disease - pathology; Apolipoproteins E - genetics; Brain Mapping; Case-Control Studies; Cell Size; Female; Genotype; Gyrus Cinguli - anatomy & histology; Gyrus Cinguli - pathology; Gyrus Cinguli - physiology; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Memory - physiology; Middle Aged; Neurofibrillary Tangles - pathology; Neurons - pathology; Postmortem Changes; Alzheimer's pathology; cingulate cortex; structural MRI; aging; cognition; histology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.2998-14.2015

This human study is based on an established cohort of “SuperAgers,” 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20–30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds ( n = 21) than in the healthy middle-aged group ( n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers ( n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50–60 year olds ( p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles ( p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons ( p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.