Background Cognitive reserve (CR) is one factor that helps to maintain cognitive function in patients with Alzheimer’s disease (AD). Whether the effects of CR depend on the semantic/executive components of the task remains unknown.
Methods 470 patients (138 with AD, 332 with mild cognitive impairment (MCI)) were selected from the Alzheimer’s Disease Neuroimaging Initiative database. Linear regression models were used to determine the effects of CR (years of education) on cognitive performance after controlling for demographic factors and regional cortical atrophy. First, we assessed memory tasks with low (Auditory Verbal Learning Test (AVLT) discriminability), moderate (AVLT delayed recall) and high (Logical Memory Test (LMT) delayed recall) executive/semantic components. Next, we assessed tasks with lower (digit span forward, Trails A) or higher (digit span backwards, Trails B) executive demands, and lower (figure copying) or higher (naming, semantic fluency) semantic demands.
Results High CR was significantly associated with performance on the LMT delayed recall, approached significance in the AVLT delayed recall and was not significantly associated with performance on AVLT discriminability. High CR was significantly associated with performance on the Trails B and digit span backwards, mildly associated with Trails A performance and was not associated with performance on digit span forwards. High CR was associated with performance on semantic but not visuospatial tasks. High CR was associated with semantic tasks in patients with both MCI and AD, but was only associated with executive functions in patients with MCI.
Conclusion CR may relate to executive functioning and semantic knowledge, leading to preserved cognitive performance in patients with AD pathology.
- Cognitive reserve
- Alzheimer’s disease
- Mild cognitive impairment
- neural compensation
- executive functioning
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Contributors The corresponding author (RRD) performed all statistical analyses. RRD: Conception of study, acquisition of data, analysis of data, writing of manuscript. MB: Acquisition of data, analysis of data. DAW: Critical revisions to the manuscript. BCD: Conception of study, critical revisions to manuscript.
Funding Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol-Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F Hoffmann-La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organisation is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Disclaimer Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (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
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with ‘BMJ Publishing Group’. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.