Cognitive resilience to three dementia-related neuropathologies in an oldest-old man: A case report from The 90+ Study

Zarui A Melikyan; María M Corrada; Anne-Marie Leiby; Seyed Ahmad Sajjadi; Syed Bukhari; Thomas J Montine; Claudia H Kawas

doi:10.1016/j.neurobiolaging.2022.03.009

Cognitive resilience to three dementia-related neuropathologies in an oldest-old man: A case report from The 90+ Study

Neurobiol Aging. 2022 Aug:116:12-15. doi: 10.1016/j.neurobiolaging.2022.03.009. Epub 2022 Mar 19.

Authors

Zarui A Melikyan¹, María M Corrada², Anne-Marie Leiby³, Seyed Ahmad Sajjadi⁴, Syed Bukhari⁵, Thomas J Montine⁵, Claudia H Kawas⁶

Affiliations

¹ Institute for Memory Impairments and Neurologic Disorders, University of California, Irvine, CA, USA. Electronic address: zmelikya@uci.edu.
² Institute for Memory Impairments and Neurologic Disorders, University of California, Irvine, CA, USA; Department of Neurology, University of California, Irvine, CA, USA; Department of Epidemiology, University of California, Irvine, CA, USA.
³ Department of Neurology, University of California, Irvine, CA, USA.
⁴ Institute for Memory Impairments and Neurologic Disorders, University of California, Irvine, CA, USA; Department of Neurology, University of California, Irvine, CA, USA.
⁵ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Institute for Memory Impairments and Neurologic Disorders, University of California, Irvine, CA, USA; Department of Neurology, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.

PMID: 35526514
PMCID: PMC9733494
DOI: 10.1016/j.neurobiolaging.2022.03.009

Abstract

Cognitive resilience provides insights into maintaining good cognition despite dementia-related neuropathologic changes. It is of special interest in the oldest-old (age 90+) because age is the strongest risk factor for dementia. We describe the only participant of The 90+ Study, among 367 autopsies, who maintained normal cognition despite intermediate-high levels of 3 dementia-related neuropathologic changes, advanced age, and comorbidities associated with cognitive impairment. This man remained cognitively normal throughout 13 semi-annual study visits, last one being 4 months before his death at 96. His cognitive test scores remained around the 90th percentile for non-timed tests and declined from 90th to 50th percentile (significant for semantic fluency) for timed tests. He remained physically and cognitively active until death, despite extrapyramidal signs in the last year of life. Neuropathological examination revealed intermediate level of Alzheimer's disease neuropathologic change (Thal phase 5, Braak NFT stage IV, CERAD score 3), Lewy bodies and neurites in the olfactory bulb, brainstem and limbic areas (Braak PD stage 4), TDP-43 inclusions in the amygdala and hippocampus (LATE stage 2), and a microvascular lesion in putamen. This case demonstrates that cognitive impairment is not inevitable even in the oldest-old with mutltiple dementia-related neuropathologic changes.

Keywords: Age 90+; Cognitive resilience; Neuropathology; Oldest-old.

Publication types

Case Reports
Research Support, N.I.H., Extramural

MeSH terms

Aged, 80 and over
Alzheimer Disease* / pathology
Cognition
Cognitive Dysfunction* / pathology
Humans
Lewy Bodies / pathology
Male
Neuropsychological Tests

Abstract

Publication types

MeSH terms

Grants and funding