4.7 Article

Subjective cognitive concerns, amyloid-β, and neurodegeneration in clinically normal elderly

Journal

NEUROLOGY
Volume 85, Issue 1, Pages 56-62

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000001712

Keywords

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Funding

  1. Alzheimer's Association [NIRG-12-243012]
  2. NIH [K23AG044431, F32AG044054, K23 AG033634, 8KL2TR000168-05, R01EB014894, R21 AG038994, R01 AG026484]
  3. Halloran Consulting Group
  4. Grifols
  5. Bayer
  6. Biogen Idec
  7. Bristol-Myers Squibb
  8. GE Healthcare
  9. Isis Pharmaceuticals Inc.
  10. Janssen Alzheimer's Immunotherapy
  11. Piramal
  12. Siemens Medical Solutions
  13. Genzyme
  14. GEHC
  15. Lundbeck
  16. Pfizer
  17. Eisai
  18. Janssen Alzheimer Immunotherapy
  19. Merck
  20. Roche
  21. Eli Lilly
  22. Fidelity Investigator-Initiated grant
  23. Alzheimer Association [SGCOG-13-282201]
  24. The NIH [R01 AG034556, P50 AG00513421, U19 AG10483, P01 AG036694, R13 AG042201174210, R01 AG027435, R01 AG037497, U01 AG032438, U01 AG024904, K24 AG035007, P50 AG005134, U19 AG010483, R01 MH090291]

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Objective: To determine whether neuroimaging biomarkers of amyloid-beta (A beta) and neurodegeneration (ND) are associated with greater self-reported subjective cognitive concerns (SCC) in clinically normal older individuals. Methods: A total of 257 participants underwent Pittsburgh compound B PET, PET with fluorodeoxyglucose F-18, and structural MRI, as well as a battery of neuropsychological measures including several questionnaires regarding SCC. Individuals were classified into 4 biomarker groups: biomarker negative (A beta-/ND-), amyloidosis alone (A beta+/ND-), amyloidosis plus ND (A beta+/ND+), and ND alone (A beta-/ND+). Results: Both A beta and ND were independently associated with greater SCC controlling for objective memory performance. By contrast, neither A beta nor ND was associated with objective memory performance controlling for SCC. Further examination revealed greater SCC in individuals with A beta or ND positivity compared to biomarker-negative individuals. In addition, greater SCC predicted A beta positivity when controlling for ND status. Conclusions: When individuals were grouped by biomarker status, those who were positive on A beta or ND had the highest report of SCC compared to biomarker-negative individuals. Findings were consistent when SCC was used to predict A beta positivity. Taken together, results suggest that both A beta and ND are associated with SCC, independent of objective memory performance. Enrichment of individuals with SCC may increase likelihood of A beta and ND markers in potential participants for secondary prevention trials.

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