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

Ossenkoppele, Rik LU ; Smith, Ruben LU ; Ohlsson, Tomas; Strandberg, Olof LU ; Mattsson, Niklas LU ; Insel, Philip S. LU ; Palmqvist, Sebastian LU and Hansson, Oskar LU (2019) In Neurology 92(6). p.601-612
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
92
issue
6
pages
601 - 612
publisher
American Academy of Neurology
external identifiers
  • scopus:85061155657
ISSN
1526-632X
DOI
10.1212/WNL.0000000000006875
language
English
LU publication?
yes
id
c15b7902-a40d-4729-99b5-0e6d12e0dff2
date added to LUP
2019-02-15 07:31:45
date last changed
2019-03-12 04:21:19
@article{c15b7902-a40d-4729-99b5-0e6d12e0dff2,
  abstract     = {<p>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 &lt; 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 &lt; 0.05), while increased [18F]flutemetamol uptake was specifically associated with lower scores on a delayed recall memory task (p &lt; 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.</p>},
  author       = {Ossenkoppele, Rik and Smith, Ruben and Ohlsson, Tomas and Strandberg, Olof and Mattsson, Niklas and Insel, Philip S. and Palmqvist, Sebastian and Hansson, Oskar},
  issn         = {1526-632X},
  language     = {eng},
  month        = {02},
  number       = {6},
  pages        = {601--612},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000006875},
  volume       = {92},
  year         = {2019},
}