Amyloid‐ β , cortical thickness, and subsequent cognitive decline in cognitively normal oldest‐old

W. Pelkmans*, N. Legdeur, M. ten Kate, F. Barkhof, M.M. Yaqub, H. Holstege, B.N.M. van Berckel, P. Scheltens, W.M. van der Flier, P.J. Visser, B.M. Tijms

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: To investigate the relationship between amyloid-beta (A beta) deposition and markers of brain structure on cognitive decline in oldest-old individuals with initial normal cognition. Methods: We studied cognitive functioning in four domains at baseline and change over time in fifty-seven cognitively intact individuals from the EMIF-AD 90+ study. Predictors were A beta status determined by [F-18]-flutemetamol PET (normal = A beta - vs. abnormal = A beta+), cortical thickness in 34 regions and hippocampal volume. Mediation analyses were performed to test whether effects of A beta on cognitive decline were mediated by atrophy of specific anatomical brain areas. Results: Subjects had a mean age of 92.7 +/- 2.9 years, of whom 19 (33%) were A beta+. Compared to A beta-, A beta+ individuals showed steeper decline on memory (beta +/- SE = -0.26 +/- 0.09), and processing speed (beta +/- SE = -0.18 +/- 0.08) performance over 1.5 years (P < 0.05). Furthermore, medial and lateral temporal lobe atrophy was associated with steeper decline in memory and language across individuals. Mediation analyses revealed that part of the memory decline observed in A beta+ individuals was mediated through parahippocampal atrophy. Interpretation: These results show that A beta abnormality even in the oldest old with initially normal cognition is not part of normal aging, but is associated with a decline in cognitive functioning. Other pathologies may also contribute to decline in the oldest old as cortical thickness predicted cognitive decline similarly in individuals with and without A beta pathology.

Original languageEnglish
Pages (from-to)348-358
Number of pages11
JournalAnnals of Clinical and Translational Neurology
Issue number2
Publication statusPublished - 1 Feb 2021


  • alzheimers-disease
  • association
  • dementia
  • deposition
  • hippocampal
  • impairment
  • memory
  • model
  • national institute
  • pathology

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