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Research Paper|Volume 13, Issue 10|pp 13430—13442

Cognitive dedifferentiation as a function of cognitive impairment in the ADNI and MemClin cohorts

John Wallert1,2, Anna Rennie1,3, Daniel Ferreira1, J-Sebastian Muehlboeck1, Lars-Olof Wahlund1, Eric Westman1,4, Urban Ekman1,5, and ADNI consortium, and MemClin steering committee
  • 1Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden
  • 2Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 3Theme Aging, Karolinska University Hospital, Stockholm, Sweden
  • 4Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King´s College, London, UK
  • 5Medical Unit Medical Psychology, Allied Health Professionals Function, Karolinska University Hospital, Stockholm, Sweden
* Shared last authorship
# Data used in preparation of this article were obtained from the Alzheimers’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Authorship_List.pdf Data used in preparation of this article were also obtained from the Stockholm MemClin study. A complete listing of the MemClin steering committee can be found at: https://ki.se/nvs/memclin
Received: December 23, 2020Accepted: May 13, 2021Published: May 26, 2021
https://doi.org/10.18632/aging.203108

Copyright: © 2021 Wallert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The cause of cognitive dedifferentiation has been suggested as specific to late-life abnormal cognitive decline rather than a general feature of aging. This hypothesis was tested in two large cohorts with different characteristics. Individuals (n = 2710) were identified in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) research database (n = 1282) in North America, and in the naturalistic multi-site MemClin Project database (n = 1223), the latter recruiting from 9 out of 10 memory clinics in the greater Stockholm catchment area in Sweden. Comprehensive neuropsychological testing informed diagnosis of dementia, mild cognitive impairment (MCI), or subjective cognitive impairment (SCI). Diagnosis was further collapsed into cognitive impairment (CI: MCI or dementia) vs no cognitive impairment (NCI). After matching, loadings on the first principal component were higher in the CI vs NCI group in both ADNI (53.1% versus 38.3%) and MemClin (33.3% vs 30.8%). Correlations of all paired combinations of individual tests by diagnostic group were also stronger in the CI group in both ADNI (mean inter-test r = 0.51 vs r = 0.33, p < 0.001) and MemClin (r = 0.31 vs r = 0.27, p = 0.042). Dedifferentiation was explained by cognitive impairment when controlling for age, sex, and education. This finding replicated across two separate, large cohorts of older individuals. Knowledge that the structure of human cognition becomes less diversified and more dependent on general intelligence as a function of cognitive impairment should inform clinical assessment and care for these patients as their neurodegeneration progresses.