| Title: |
Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis |
| Authors: |
Bocancea, Diana I; Svenningsson, Anna L; van Loenhoud, Anna C; Groot, Colin; Barkhof, Frederik; Strandberg, Olof; Smith, Ruben; Weiner, Michael W; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J; Morris, John C; Perrin, Richard J; Shaw, Leslie M; Khachaturian, Zaven; Carrillo, Maria; Potter, William; Barnes, Lisa; Bernard, Marie; González, Hector; Ho, Carole; Hsiao, John K; Jackson, Jonathan; Masliah, Eliezer; Masterman, Donna; Okonkwo, Ozioma; Ryan, Laurie; Silverberg, Nina; Fleisher, Adam; Sacrey, Diana Truran; Fockler, Juliet; Conti, Cat; Veitch, Dallas; Neuhaus, John; Jin, Chengshi; Nosheny, Rachel; Ashford, Miriam; Flenniken, Derek; Kormo, Adrienne; Montine, Tom; Conti, Cat B; Rafii, Michael; Raman, Rema; Jimenez, Gustavo; Donohue, Michael; Gessert, Devon; Salazar, Jennifer; Zimmerman, Caileigh; Cabrera, Yuliana; Walter, Sarah; Miller, Garrett; Coker, Godfrey; Clanton, Taylor; Hergesheimer, Lindsey; Smith, Stephanie; Adegoke, Olusegun; Mahboubi, Payam; Moore, Shelley; Pizzola, Jeremy; Shaffer, Elizabeth; Harvey, Danielle; Forghanian-Arani, Arvin; Borowski, Bret; Ward, Chad; Schwarz, Christopher; Jones, David; Gunter, Jeff; Kantarci, Kejal; Senjem, Matthew; Vemuri, Prashanthi; Reid, Robert; Fox, Nick C; Malone, Ian; Thompson, Paul; Thomopoulos, Sophia I; Nir, Talia M; Jahanshad, Neda; DeCarli, Charles; Knaack, Alexander; Fletcher, Evan; Tosun-Turgut, Duygu; Chen, Stephanie Rossi; Choe, Mark; Crawfor, Karen |
| Source: |
Brain, vol 146, iss 9 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2023 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
42 Health Sciences (for-2020); Alzheimer's Disease (rcdc); Neurosciences (rcdc); Neurodegenerative (rcdc); Dementia (rcdc); Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) (rcdc); Vascular Cognitive Impairment/Dementia (rcdc); Brain Disorders (rcdc); Biomedical Imaging (rcdc); Alzheimer's Disease Related Dementias (ADRD) (rcdc); Behavioral and Social Science (rcdc); Aging (rcdc); Cerebrovascular (rcdc); Clinical Research (rcdc); Acquired Cognitive Impairment (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); 1.1 Normal biological development and functioning (hrcs-rac); Mental health (hrcs-hc); Neurological (hrcs-hc); Humans (mesh); Alzheimer Disease (mesh); Longitudinal Studies (mesh); tau Proteins (mesh); Cross-Sectional Studies (mesh); Cerebral Cortical Thinning (mesh); Positron-Emission Tomography (mesh); Brain (mesh); Cognition (mesh); Apolipoproteins E (mesh); Alzheimer's disease |
| Time: |
3719 - 3734 |
| Description: |
Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt7033j2n6; https://escholarship.org/uc/item/7033j2n6; https://escholarship.org/content/qt7033j2n6/qt7033j2n6.pdf |
| DOI: |
10.1093/brain/awad100 |
| Availability: |
https://escholarship.org/uc/item/7033j2n6; https://escholarship.org/content/qt7033j2n6/qt7033j2n6.pdf; https://doi.org/10.1093/brain/awad100 |
| Rights: |
CC-BY-NC |
| Accession Number: |
edsbas.2642DBA9 |
| Database: |
BASE |