Neuropsychology Review

, Volume 27, Issue 4, pp 305–325 | Cite as

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

  • S. Duke HanEmail author
  • Caroline P. Nguyen
  • Nikki H. Stricker
  • Daniel A. Nation


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.


Cognition Preclinical Alzheimer’s disease Biomarker Meta-analysis 



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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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • S. Duke Han
    • 1
    • 2
    • 3
    • 4
    Email author
  • Caroline P. Nguyen
    • 1
  • Nikki H. Stricker
    • 5
  • Daniel A. Nation
    • 3
  1. 1.Department of Family MedicineUSC Keck School of MedicineAlhambraUSA
  2. 2.Department of NeurologyUSC Keck School of MedicineLos AngelesUSA
  3. 3.Department of PsychologyUSC Dornsife CollegeLos AngelesUSA
  4. 4.USC School of GerontologyLos AngelesUSA
  5. 5.Department of Psychiatry and PsychologyMayo ClinicRochesterUSA

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