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Detectable Neuropsychological Differences in Early Preclinical Alzheimer’s Disease: A Meta-Analysis

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A Correction to this article was published on 23 December 2017

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Abstract

The development of methods for in vivo detection of cerebral beta amyloid retention and tau accumulation have been increasingly useful in characterizing preclinical Alzheimer’s disease (AD). While the association between these biomarkers and eventual AD has been demonstrated among cognitively intact older adults, the link between biomarkers and neurocognitive ability remains unclear. We conducted a meta-analysis to test the hypothesis that cognitively intact older adults would show statistically discernable differences in neuropsychological performance by amyloid status (amyloid negative = A-, amyloid positive = A+). We secondarily hypothesized a third group characterized by either CSF tau pathology or neurodegeneration, in addition to amyloidosis (A+/N+ or Stage 2), would show lower neuropsychology scores than the amyloid positive group (A+/N- or Stage 1) when compared to the amyloid negative group. Pubmed, PsychINFO, and other sources were searched for relevant articles, yielding 775 total sources. After review for inclusion/exclusion criteria, duplicates, and risk of bias, 61 studies were utilized in the final meta-analysis. Results showed A+ was associated with poorer performance in the domains of global cognitive function, memory, language, visuospatial ability, processing speed, and attention/working memory/executive functions when compared to A-. A+/N+ showed lower performances on memory measures when compared to A+/N- in secondary analyses based on a smaller subset of studies. Results support the notion that neuropsychological measures are sensitive to different stages of preclinical AD among cognitively intact older adults. Further research is needed to determine what constitutes meaningful differences in neuropsychological performance among cognitively intact older adults.

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  • 23 December 2017

    Errors were discovered in the reporting of processing speed data that do not impact the interpretation of findings.

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Acknowledgments

SDH is supported by National Institute on Aging grant K23AG040625, and the American Federation for Aging Research (AFAR). NHS serves as a consultant to Biogen. The funding agencies had no role in this study.

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Authors and Affiliations

  1. Department of Family Medicine, USC Keck School of Medicine, 1000 S. Fremont Avenue, Unit 22, HSA Building A-6, 4th Floor, Room 6437A, Alhambra, CA, 91803, USA

    S. Duke Han & Caroline P. Nguyen

  2. Department of Neurology, USC Keck School of Medicine, Los Angeles, CA, USA

    S. Duke Han

  3. Department of Psychology, USC Dornsife College, Los Angeles, CA, USA

    S. Duke Han & Daniel A. Nation

  4. USC School of Gerontology, Los Angeles, CA, USA

    S. Duke Han

  5. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

    Nikki H. Stricker

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Correspondence to S. Duke Han.

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A correction to this article is available online at https://doi.org/10.1007/s11065-017-9366-0.

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Duke Han, S., Nguyen, C.P., Stricker, N.H. et al. Detectable Neuropsychological Differences in Early Preclinical Alzheimer’s Disease: A Meta-Analysis. Neuropsychol Rev 27, 305–325 (2017). https://doi.org/10.1007/s11065-017-9345-5

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