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

Abstract

This human study is based on an established cohort of "SuperAgers," 80ϩ-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 80ϩ year olds (n ϭ 21) than in the healthy middle-aged group (n ϭ 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n ϭ 31) compared with cognitively average 80ϩ year olds and also to the much younger healthy 50 -60 year olds (p Ͻ 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 Ͻ 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 Ͻ 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.

Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

“…Remarkably, this group of superagers exhibited full preservation of cortical thickness in several of these regions. Prior studies on the cortical neuroanatomy of superagers has called attention to the preservation of thickness of part of the cingulate cortex-a nearly identical anterior midcingulate region as we observed here (Harrison et al, 2012;Rogalski et al, 2013;Gefen et al, 2015). The comparison of superagers to typical older adults shown in Figure 1d of Harrison et al (2012) demonstrates preserved thickness in some of the other regions we found, including rostral medial PFC, anterior insula, superior frontal gyrus, and angular gyrus.…”

“…All participants were required to score within 1.5 SDs of published normative values for each neuropsychological instrument on the basis of their age and education. To be designated as a superager, an elderly adult was required to meet two strict psychometric criteria similar to previous studies (Harrison et al 2012;Rogalski et al, 2013;Gefen et al, 2014). First, they were required to perform at or above the mean gender-adjusted value for young adults (age range, 18 -32) on the Long Delay Free Recall measure of the CVLT (CVLT-LD).…”

“…Participants arrived at the lab on Day 1 to complete a neuropsychological battery of tests, including the CVLT (Delis et al, 1987); TMT (Reitan, 1958;Strauss et al, 2006); portions of the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery (Kramer et al, 2014) including Flanker and the Continuous Performance Task, 1-and 2-back; and the Mini-Mental State Examination (MMSE; Folstein et al, 1975). On Day 2 (1-3 d later), participants completed a standardized MRI scan from which measurements of neuroanatomy were obtained.…”

“…Harrison et al (2012), Rogalski et al (2013), and Gefen et al (2014 coined the term superagers to refer to people over age 80 who perform at or above normative values for individuals in their 50s and 60s on a verbal long delay free recall test. We expanded the definition to a younger group of older adults, near or just older than typical retirement age (60 -80 years old), in part because prior research has shown an inflection point in some cognitive abilities including memory at around age 65 (McDaniel et al, 2008;Rogalski et al, 2013).…”

“…Nevertheless, there is substantial variation in the degree of cognitive decline with age. Some older adults-referred to by one group as "superagers"-continue to perform at a level similar to middle-aged adults (Harrison et al, 2012;Rogalski et al, 2013;Gefen et al, 2014;Gefen et al, 2015), and sometimes even young adults (Weintraub et al, 1994). Investigation of the biological mechanisms associated with "youthful" cognitive function in such individuals is crucial to understanding "successful aging" (Depp and Jeste, 2006).…”