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Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline

Ossenkoppele, Rik LU ; Pichet Binette, Alexa LU ; Groot, Colin LU ; Smith, Ruben LU ; Strandberg, Olof LU ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; Tideman, Pontus LU ; Ohlsson, Tomas and Jögi, Jonas LU orcid , et al. (2022) In Nature Medicine 28(11). p.2381-2387
Abstract

A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T- and A-T- groups. Cox... (More)

A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T- and A-T- groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A+TNEO-T+ (hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9-33.7), A+TMTL+ (HR = 14.6, 95% CI = 8.1-26.4) and A+T- (HR = 2.4, 95% CI = 1.4-4.3) groups versus the A-T- (reference) group. Both A+TMTL+ (HR = 6.0, 95% CI = 3.4-10.6) and A+TNEO-T+ (HR = 7.9, 95% CI = 4.7-13.5) groups also showed faster clinical progression to mild cognitive impairment than the A+T- group. Linear mixed-effect models indicated that the A+TNEO-T+ (β = -0.056 ± 0.005, T = -11.55, P < 0.001), A+TMTL+ (β = -0.024 ± 0.005, T = -4.72, P < 0.001) and A+T- (β = -0.008 ± 0.002, T = -3.46, P < 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A-T- (reference) group (all P < 0.001). Both A+TNEO-T+ (P < 0.001) and A+TMTL+ (P = 0.002) groups also progressed faster than the A+T- group. In summary, evidence of advanced Alzheimer's disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3-5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.

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Contribution to journal
publication status
published
subject
keywords
Humans, Alzheimer Disease/pathology, tau Proteins/metabolism, Brain/metabolism, Cognitive Dysfunction/diagnostic imaging, Positron-Emission Tomography/methods, Amyloid/metabolism, Amyloid beta-Peptides/metabolism, Amyloidosis, Plaque, Amyloid, Biomarkers
in
Nature Medicine
volume
28
issue
11
pages
7 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:36357681
  • scopus:85141678180
ISSN
1546-170X
DOI
10.1038/s41591-022-02049-x
language
English
LU publication?
yes
id
708ac86f-22eb-4397-a375-420c089e86b5
date added to LUP
2022-11-28 13:10:47
date last changed
2024-06-15 01:18:50
@article{708ac86f-22eb-4397-a375-420c089e86b5,
  abstract     = {{<p>A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T- and A-T- groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A+TNEO-T+ (hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9-33.7), A+TMTL+ (HR = 14.6, 95% CI = 8.1-26.4) and A+T- (HR = 2.4, 95% CI = 1.4-4.3) groups versus the A-T- (reference) group. Both A+TMTL+ (HR = 6.0, 95% CI = 3.4-10.6) and A+TNEO-T+ (HR = 7.9, 95% CI = 4.7-13.5) groups also showed faster clinical progression to mild cognitive impairment than the A+T- group. Linear mixed-effect models indicated that the A+TNEO-T+ (β = -0.056 ± 0.005, T = -11.55, P &lt; 0.001), A+TMTL+ (β = -0.024 ± 0.005, T = -4.72, P &lt; 0.001) and A+T- (β = -0.008 ± 0.002, T = -3.46, P &lt; 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A-T- (reference) group (all P &lt; 0.001). Both A+TNEO-T+ (P &lt; 0.001) and A+TMTL+ (P = 0.002) groups also progressed faster than the A+T- group. In summary, evidence of advanced Alzheimer's disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3-5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.</p>}},
  author       = {{Ossenkoppele, Rik and Pichet Binette, Alexa and Groot, Colin and Smith, Ruben and Strandberg, Olof and Palmqvist, Sebastian and Stomrud, Erik and Tideman, Pontus and Ohlsson, Tomas and Jögi, Jonas and Johnson, Keith and Sperling, Reisa and Dore, Vincent and Masters, Colin L and Rowe, Christopher and Visser, Denise and van Berckel, Bart N M and van der Flier, Wiesje M and Baker, Suzanne and Jagust, William J and Wiste, Heather J and Petersen, Ronald C and Jack, Clifford R and Hansson, Oskar}},
  issn         = {{1546-170X}},
  keywords     = {{Humans; Alzheimer Disease/pathology; tau Proteins/metabolism; Brain/metabolism; Cognitive Dysfunction/diagnostic imaging; Positron-Emission Tomography/methods; Amyloid/metabolism; Amyloid beta-Peptides/metabolism; Amyloidosis; Plaque, Amyloid; Biomarkers}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2381--2387}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline}},
  url          = {{http://dx.doi.org/10.1038/s41591-022-02049-x}},
  doi          = {{10.1038/s41591-022-02049-x}},
  volume       = {{28}},
  year         = {{2022}},
}