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Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis

Journal Article · · Brain
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  1. Vrije Univ., Amsterdam (Netherlands); Amsterdam Neuroscience, Neurodegeneration, Amsterdam (Netherlands); Alzheimer’s Disease Neuroimaging Initiative (ADNI). et al.
  2. Clinical Memory Research Unit, Lund University , 211 46 Lund , Sweden
  3. Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HZ Amsterdam , The Netherlands; Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam , The Netherlands
  4. Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HZ Amsterdam , The Netherlands; Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam , The Netherlands; Clinical Memory Research Unit, Lund University , 211 46 Lund , Sweden
  5. Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC , 1081 HV Amsterdam , The Netherlands; Queen Square Institute of Neurology and Center for Medical Image Computing, University College London , London WC1N 3BG , UK
  6. Clinical Memory Research Unit, Lund University , 211 46 Lund , Sweden; Department of Neurology, Skåne University Hospital , 221 84 Lund , Sweden
  7. Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 , USA
  8. Avid Radiopharmaceuticals , Philadelphia, PA 19104 , USA
  9. Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 , USA; Department of Radiology and Biomedical Imaging, University of California , San Francisco, CA 94143 , USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory , Berkeley, CA 94720 , USA
  10. Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc , 1081 HZ Amsterdam , The Netherlands; Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam , The Netherlands; Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC , 1081 HV Amsterdam , The Netherlands
  11. Clinical Memory Research Unit, Lund University , 211 46 Lund , Sweden; Memory Clinic, Skåne University Hospital , 214 28 Malmö , Sweden
+ Show Author Affiliations
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, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
Alzheimer’s Association; National Institutes of Health (NIH); USDOE
Contributing Organization:
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2470637
Journal Information:
Brain, Journal Name: Brain Journal Issue: 9 Vol. 146; ISSN 0006-8950
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

References (70)

Discriminative Accuracy of [ 18 F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders journal September 2018
Association of Apolipoprotein E ɛ4, Educational Level, and Sex With Tau Deposition and Tau-Mediated Metabolic Dysfunction in Older Adults journal October 2019
Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau journal August 2018
Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults journal May 2019
Association of Apolipoprotein E ε4 With Medial Temporal Tau Independent of Amyloid-β journal April 2020
Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease journal May 2020
Positron Emission Tomography Imaging With [ 18 F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes journal July 2020
Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease journal August 2021
Tau positron emission tomographic imaging in aging and early Alzheimer disease: Tau PET in Aging and Early AD journal December 2015
The impact of Aβ and tau on prospective cognitive decline in older individuals journal December 2018
Longitudinal tau accumulation and atrophy in aging and alzheimer disease: Tau-PET and Atrophy journal January 2019
Sex Mediates Relationships Between Regional Tau Pathology and Cognitive Decline journal August 2020
Intracranial volume in mild cognitive impairment, Alzheimer's disease and vascular dementia: evidence for brain reserve? journal September 2004
AFNI: Software for Analysis and Visualization of Functional Magnetic Resonance Neuroimages journal June 1996
Level of education mitigates the impact of tau pathology on neuronal function journal June 2019
The impact of demographic, clinical, genetic, and imaging variables on tau PET status journal November 2020
Sex differences in the association between AD biomarkers and cognitive decline journal February 2016
Cognitive resilience in clinical and preclinical Alzheimer’s disease: the Association of Amyloid and Tau Burden on cognitive performance journal October 2016
Understanding the Odd Science of Aging journal February 2005
Intelligence and educational achievement journal January 2007
Defining imaging biomarker cut points for brain aging and Alzheimer's disease journal March 2017
Transitions across cognitive states and death among older adults in relation to education: A multistate survival model using data from six longitudinal studies journal February 2018
Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance journal January 2020
Tau pathology and cognitive reserve in Alzheimer's disease journal September 2017
Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve journal August 2018
Associations between baseline amyloid, sex, and APOE on subsequent tau accumulation in cerebrospinal fluid journal June 2019
Education does not protect cognitive function from brain pathology in the ADNI 2 cohort journal June 2020
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest journal July 2006
Within-subject template estimation for unbiased longitudinal image analysis journal July 2012
PET Imaging of Tau Deposition in the Aging Human Brain journal March 2016
Cognitive reserve☆ journal August 2009
When does education matter? The protective effect of education for cohorts graduating in bad times journal February 2015
Effects of age and naturally occurring experience on spatial visualization performance. journal September 1990
Brain reserve capacity on symptom onset after brain injury: A formulation and review of evidence for threshold theory. journal July 1993
The ageing cortical synapse: hallmarks and implications for cognitive decline journal March 2012
Specification curve analysis journal July 2020
Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing journal October 2018
Predicting future rates of tau accumulation on PET journal June 2020
The accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects journal December 2020
Compensatory mechanisms in higher-educated subjects with Alzheimer’s disease: a study of 20 years of cognitive decline journal February 2014
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease journal March 2016
Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer’s disease journal July 2017
Widespread brain tau and its association with ageing, Braak stage and Alzheimer’s dementia journal December 2017
A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer’s disease dementia journal April 2019
Education and Cognitive Decline: An Integrative Analysis of Global Longitudinal Studies of Cognitive Aging journal May 2019
Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship journal January 2009
Clinicopathologic Correlations in a Large Alzheimer Disease Center Autopsy Cohort journal December 2007
The Mini-Mental State Examination: A Comprehensive Review journal September 1992
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing journal January 1995
Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET journal January 2020
Tau-PET imaging predicts cognitive decline and brain atrophy progression in early Alzheimer’s disease journal February 2022
Education and rates of cognitive decline in incident Alzheimer's disease journal July 2005
Cognitive Aging and Dementia: A Life-Span Perspective journal December 2019
Normalized Mini-Mental State Examination for Assessing Cognitive Change in Population-Based Brain Aging Studies journal January 2014
Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer’s disease: a cohort study journal August 2018
Is intracranial volume a suitable proxy for brain reserve? journal September 2018
Verbal intelligence is a more robust cross-sectional measure of cognitive reserve than level of education in healthy older adults journal July 2021
Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone journal June 2020
Education and the course of cognitive decline in Alzheimer disease journal October 2004
Resistance vs resilience to Alzheimer disease journal March 2018
Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease journal January 2019
Education and cognitive reserve in old age journal March 2019
Sex differences in CSF biomarkers vary by Alzheimer disease stage and APOE ε4 genotype journal October 2020
Measuring Resilience and Resistance in Aging and Alzheimer Disease Using Residual Methods journal September 2021
Association of Education and Intracranial Volume With Cognitive Trajectories and Mortality Rates Across the Alzheimer Disease Continuum journal April 2022
Cortical thickness and its associations with age, total cognition and education across the adult lifespan journal March 2020
Progressive Tau Accumulation in Alzheimer Disease: 2-Year Follow-up Study journal March 2019
Socioeconomic Status and Academic Achievement: A Meta-Analytic Review of Research journal September 2005
The Risk of Dementia in Relation to Cognitive and Brain Reserve journal September 2020
Cognitive Reserve and Related Constructs: A Unified Framework Across Cognitive and Brain Dimensions of Aging journal May 2022

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Alzheimer’s disease
MRI
Neurosciences & Neurology
PET
cognition
resilience
tau