Acta Neuropathologica

, Volume 136, Issue 3, pp 377–388 | Cite as

Non-Alzheimer’s contributions to dementia and cognitive resilience in The 90+ Study

  • John L. Robinson
  • Maria M. Corrada
  • Gabor G. Kovacs
  • Myrna Dominique
  • Carrie Caswell
  • Sharon X. Xie
  • Virginia M.-Y. Lee
  • Claudia H. Kawas
  • John Q. TrojanowskiEmail author
Original Paper


The diagnosis of Alzheimer’s disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models—adjusting for age, sex and education—determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to cognitive resilience in the oldest-old.



We wish to thank the participants and their relatives, testers and examiners of The 90+ Study, and the staff of the UCI brain repository for making this study possible. We also thank Terry Schuck and Katie Casalnova for their assistance with this study. Funding from the National Institutes of Health (AG10124, AG16573, AG17586, R01AG021055, R01AG042444, P50AG16573 and MH64045) supported this study.

Supplementary material

401_2018_1872_MOESM1_ESM.docx (1007 kb)
Supplementary material 1 (DOCX 1007 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • John L. Robinson
    • 1
  • Maria M. Corrada
    • 2
  • Gabor G. Kovacs
    • 1
    • 3
  • Myrna Dominique
    • 1
  • Carrie Caswell
    • 4
  • Sharon X. Xie
    • 4
  • Virginia M.-Y. Lee
    • 1
  • Claudia H. Kawas
    • 5
  • John Q. Trojanowski
    • 1
    Email author
  1. 1.Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease ResearchInstitute on Aging, University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Neurology, Department of Epidemiology, Institute for Memory Impairments and Neurological DisordersUniversity of California at IrvineIrvineUSA
  3. 3.Institute of NeurologyMedical University of ViennaViennaAustria
  4. 4.Department of Biostatistics, Epidemiology and InformaticsUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of Neurology, Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological DisordersUniversity of California at IrvineIrvineUSA

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