Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease
| Autor: | Bejanin, Alexandre, Schonhaut, Daniel R, La Joie, Renaud, Kramer, Joel H, Baker, Suzanne L, Sosa, Natasha, Ayakta, Nagehan, Cantwell, Averill, Janabi, Mustafa, Lauriola, Mariella, O'Neil, James P, Gorno-Tempini, Maria L, Miller, Zachary A, Rosen, Howard J, Miller, Bruce L, Jagust, William J, Rabinovici, Gil D |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Fluorine Radioisotopes Amyloid Aging Primary Progressive tau Proteins Neuropsychological Tests Neurodegenerative Alzheimer's Disease Medical and Health Sciences atrophy Alzheimer Disease Clinical Research Aphasia Acquired Cognitive Impairment Humans 2.1 Biological and endogenous factors Cognitive Dysfunction Carbon Radioisotopes Benzothiazoles tau Aetiology Aged cognitive impairment Aniline Compounds Neurology & Neurosurgery Psychology and Cognitive Sciences Neurosciences Brain Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Middle Aged Magnetic Resonance Imaging Brain Disorders Thiazoles Positron-Emission Tomography Case-Control Studies Neurological Regression Analysis Biomedical Imaging Female Dementia Alzheimer’s disease Carbolines |
| Zdroj: | Bejanin, A; Schonhaut, DR; La Joie, R; Kramer, JH; Baker, SL; Sosa, N; et al.(2017). Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease. Brain, 140(12), 3286-3300. doi: 10.1093/brain/awx243. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/9ms625vc Brain : a journal of neurology, vol 140, iss 12 |
| DOI: | 10.1093/brain/awx243. |
| Popis: | © 2017 The Author. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable Alzheimer's disease dementia (n = 35). Twelve patients additionally fulfilled the diagnostic criteria for posterior cortical atrophy and eight for logopenic variant primary progressive aphasia. All participants underwent 3T magnetic resonance imaging, amyloid (11C-PiB) positron emission tomography and tau (18F-AV-1451) positron emission tomography, and episodic and semantic memory, language, executive and visuospatial functions assessment. Raw cognitive scores were converted to age-adjusted Z-scores (W-scores) and averaged to compute composite scores for each cognitive domain. Independent regressions were performed between18F-AV-1451 binding and each cognitive domain, and we used the Biological Parametric Mapping toolbox to further control for local grey matter volumes,11C-PiB uptake, or both. Partial correlations and causal mediation analyses (mediation R package) were then performed in brain regions showing an association between cognition and both18F-AV-1451 uptake and grey matter volume. Our results showed that decreased cognitive performance in each domain was related to increased18F-AV-1451 binding in specific brain regions conforming to established brain-behaviour relationships (i.e. episodic memory: medial temporal lobe and angular gyrus; semantic memory: left anterior temporal regions; language: left posterior superior temporal lobe and supramarginal gyrus; executive functions: bilateral frontoparietal regions; visuospatial functions: right more than left occipitotemporal regions). This pattern of regional associations remained essentially unchanged-although less spatially extended-when grey matter volume or11C-PiB uptake maps were added as covariates. Mediation analyses revealed both direct and grey matter-mediated effects of18FAV-1451 uptake on cognitive performance. Together, these results show that tau pathology is related in a region-specific manner to cognitive impairment in Alzheimer's disease. These regional relationships are weakly related to amyloid burden, but are in part mediated by grey matter volumes. This suggests that tau pathology may lead to cognitive deficits through a variety of mechanisms, including, but not restricted to, grey matter loss. These results might have implications for future therapeutic trials targeting tau pathology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|