Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease

Neurology. 2019 Feb 5;92(6):e601-e612. doi: 10.1212/WNL.0000000000006875. Epub 2019 Jan 9.


Objective: To examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD).

Methods: We included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairment), and 48 had probable AD dementia. All underwent [18F]flortaucipir (tau) and structural MRI (cortical thickness), and 88 of 106 underwent [18F]flutemetamol (Aβ) PET. Linear regression models adjusted for age, sex, and education were performed to examine associations between 7 regions of interest and 7 neuropsychological tests for all 3 imaging modalities.

Results: In preclinical AD, [18F]flortaucipir, but not [18F]flutemetamol or cortical thickness, was associated with decreased global cognition, memory, and processing speed (range standardized β = 0.35-0.52, p < 0.05 uncorrected for multiple comparisons). In the combined prodromal AD and AD dementia group, both increased [18F]flortaucipir uptake and reduced cortical thickness were associated with worse performance on a variety of neuropsychological tests (most regions of interest survived correction for multiple comparisons at p < 0.05), while increased [18F]flutemetamol uptake was specifically associated with lower scores on a delayed recall memory task (p < 0.05 uncorrected for multiple comparisons). The strongest effects for both [18F]flortaucipir and cortical thickness on cognition were found in the lateral and medial parietal cortex and lateral temporal cortex. The effect of [18F]flutemetamol on cognition was generally weaker and less region specific.

Conclusion: Our findings suggest that tau PET is more sensitive than Aβ PET and measures of cortical thickness for detecting early cognitive changes in preclinical AD. Furthermore, both [18F]flortaucipir PET and cortical thickness show strong cognitive correlates at the clinical stages of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Aniline Compounds
  • Benzothiazoles
  • Carbolines
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cognition*
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / psychology
  • Contrast Media
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Organ Size
  • Positron-Emission Tomography
  • Prodromal Symptoms
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Carbolines
  • Contrast Media
  • MAPT protein, human
  • tau Proteins
  • flutemetamol
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole