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- Groot, Colin, et al.
(författare)
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Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-β–negative cognitively normal individuals
- 2021
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 97, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether mesial temporal (Me) tau relates to cognitive performance in 47 amyloid-β (Aβ)-negative, cognitively normal older adults (>60 years old). Me-tau was measured using [18F]flortaucipir–positron emission tomography standardized uptake value ratio. The effect of continuous and categorical (stratified at standardized uptake value ratio = 1.2 [21% Me-positive]) Me-tau on cognition (mini-mental state examination, pre-Alzheimer's cognitive composite, a memory composite, and a nonmemory composite score) was examined using general linear models, and associations between Me-tau and [18F]flortaucipir signal in the neocortex were assessed using voxelwise regressions (continuous) and voxelwise contrasts (categorical). In addition, we assessed the effect of age and Aβ burden on Me-tau. Both continuous and categorical Me-tau was associated with worse cognitive performance across all tests and with higher lateral temporal and parietal [18F]flortaucipir signal. Furthermore, we observed a marginal association between Me-tau and age, whereas there was no association with Aβ burden. Our findings indicate that Me-tau in Aβ-negative cognitively normal individuals, which is likely age-related (i.e., primary age-related tauopathy), might not be as benign as commonly thought.
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| 2. |
- Ossenkoppele, Rik, et al.
(författare)
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Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:11, s. 2381-2387
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Tidskriftsartikel (refereegranskat)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.
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