Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression
| Autor: | Rebecca E. Amariglio, Mykol Larvie, Gad A. Marshall, Elizabeth C. Mormino, Aaron P. Schultz, Andrew Ward, Keith A. Johnson, Dorene M. Rentz, Sarah E. Wigman, Reisa A. Sperling, Willem Huijbers |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
medicine.diagnostic_test Clinical Dementia Rating Hippocampus Magnetic resonance imaging Cognition Hippocampal formation medicine.disease chemistry.chemical_compound Atrophy chemistry Internal medicine mental disorders medicine Cardiology Dementia Neurology (clinical) Pittsburgh compound B Psychology Neuroscience |
| Zdroj: | Brain. 138:1023-1035 |
| ISSN: | 1460-2156 0006-8950 |
| Popis: | Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model, amyloid-β status, hippocampal activation, and hippocampal volume independently predicted clinical progression. These results indicate that amyloid-β positive patients with mild cognitive impairment are more likely on a path towards Alzheimer's disease dementia than amyloid-β negative patients. Increased hippocampal activity is discussed in relation to neuronal compensation and/or amyloid-β induced excitoxicity. |
| Databáze: | OpenAIRE |
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