Abstract
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 language | English |
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Pages (from-to) | 348-358 |
Number of pages | 11 |
Journal | Annals of Clinical and Translational Neurology |
Volume | 8 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Feb 2021 |
Keywords
- alzheimers-disease
- association
- dementia
- deposition
- hippocampal
- impairment
- memory
- model
- national institute
- pathology
- DEMENTIA
- ALZHEIMERS-DISEASE
- DEPOSITION
- HIPPOCAMPAL
- PATHOLOGY
- MODEL
- IMPAIRMENT
- NATIONAL INSTITUTE
- MEMORY
- ASSOCIATION