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Title: Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline.
Austin Authors: Ossenkoppele, Rik;Pichet Binette, Alexa;Groot, Colin;Smith, Ruben;Strandberg, Olof;Palmqvist, Sebastian;Stomrud, Erik;Tideman, Pontus;Ohlsson, Tomas;Jögi, Jonas;Johnson, Keith;Sperling, Reisa;Doré, Vincent ;Masters, Colin L ;Rowe, Christopher C ;Visser, Denise;van Berckel, Bart N M;van der Flier, Wiesje M;Baker, Suzanne;Jagust, William J;Wiste, Heather J;Petersen, Ronald C;Jack, Clifford R;Hansson, Oskar
Affiliation: Lund University, Clinical Memory Research Unit, Lund, Sweden.
Department of Radiation Physics, Skåne University Hospital, Lund, Sweden.
Skåne University Hospital, Department of Clinical Physiology and Nuclear Medicine, Lund, Sweden.
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
The Australian e-Health Research Centre CSIRO Melbourne Victoria Australia, Melbourne, Victoria, Australia.
The Florey Institute of Neuroscience and Mental Health
Molecular Imaging and Therapy
Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands.
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Issue Date: Nov-2022
Date: 2022
Publication information: Nature Medicine 2022
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 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.
DOI: 10.1038/s41591-022-02049-x
ORCID: 0000-0003-1584-7477
Journal: Nature Medicine
Start page: 2381
End page: 2387
PubMed URL: 36357681
ISSN: 1546-170X
Type: Journal Article
Subjects: Amyloid
tau PET-positive cognitively unimpaired
Alzheimer Disease/pathology
tau Proteins/metabolism
Cognitive Dysfunction/diagnostic imaging
Positron-Emission Tomography/methods
Amyloid beta-Peptides/metabolism
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