TY - JOUR
T1 - Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline
AU - Ossenkoppele, Rik
AU - Pichet Binette, Alexa
AU - Groot, Colin
AU - Smith, Ruben
AU - Strandberg, Olof
AU - Palmqvist, Sebastian
AU - Stomrud, Erik
AU - Tideman, Pontus
AU - Ohlsson, Tomas
AU - Jögi, Jonas
AU - Johnson, Keith
AU - Sperling, Reisa
AU - Dore, Vincent
AU - Masters, Colin L.
AU - Rowe, Christopher
AU - Visser, Denise
AU - van Berckel, Bart N.M.
AU - van der Flier, Wiesje M.
AU - Baker, Suzanne
AU - Jagust, William J.
AU - Wiste, Heather J.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Hansson, Oskar
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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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U2 - 10.1038/s41591-022-02049-x
DO - 10.1038/s41591-022-02049-x
M3 - Article
C2 - 36357681
AN - SCOPUS:85141678180
SN - 1078-8956
VL - 28
SP - 2381
EP - 2387
JO - Nature Medicine
JF - Nature Medicine
IS - 11
ER -