Affiliations: [a]
Department of Neurology, University of California, Irvine, CA, USA
| [b]
Department of Neurobiology and Behavior, University of California, Irvine, CA, USA
| [c]
Department of Pathology, Stanford University, Palo Alto, CA, USA
| [d]
Department of Epidemiology and Biostatistics, University of California, Irvine, CA, USA
Correspondence:
[*]
Correspondence to: Roshni Biswas, University of California, Irvine, Hewitt Hall Room 1515, Irvine, CA 92697, USA. Tel.: +1 949 824 9176; E-mail: roshni.biswas@uci.edu and Maria M. Corrada, University of California, Irvine, Hewitt Hall Room 1513, Irvine, CA 92697, USA. Tel.: +1 949 824 9109; E-mail: mcorrada@uci.edu.
Abstract: Background:Some oldest-old individuals can maintain superior cognition despite advanced age. Little is known about the neuropathological changes in the brains of oldest-old superior cognitive performers. Objective:Our objective was to examine the associations between Alzheimer’s disease (AD) and non-AD neuropathologic features in relation to superior cognitive performance in oldest-old individuals. Methods:We analyzed brain autopsy data from 102 participants with normal cognition from The 90+ Study. Superior global cognitive performers (SGCP) were defined as having Mini-Mental State Examination (MMSE) score ≥28 in the last visit 12 to 2 months before death. To examine the associations between individual and multiple comorbid neuropathologic features with SGCP status we used multiple logistic regression models adjusting for age, sex, and education. Results:Alzheimer’s disease neuropathological change (ADNC) and low levels of vascular pathologic change were not associated with superior cognition. In contrast, participants with limbic (OR = 8.37; 95% CI: 1.48–47.44) and neocortical (OR = 10.80;95% CI: 1.03–113.82) Lewy body disease (LBD), or with hippocampal sclerosis (HS) (OR = 5.28; 95% CI: 1.10–25.47) were more likely to be non-SGCP. High total burden of multiple comorbid neuropathologic features was associated with a lower likelihood of being SGCP. Conclusion:Oldest-old superior cognitive performers were resilient to ADNC and low levels of vascular pathologic change and were resistant to non-AD neurodegenerative changes and multiple comorbid neuropathologic features. Understanding the factors underlying the ability of superior cognitive performers to resist these changes might provide useful insights on maintenance of superior cognition despite advanced age.
