In:
Alzheimer's & Dementia, Wiley, Vol. 17, No. S4 ( 2021-12)
Abstract:
Previous reports have shown that elevated AD biomarkers among clinically normal (CN) older adults confer heightened risk for a subsequent diagnosis of cognitive impairment using CSF and amyloid imaging. Here, we examine the impact of biomarker status on neuroimaging for both amyloid(A+/A‐) and tau(T+/T‐) on risk for clinical progression. Method Participants were CN at enrollment and underwent PET with 11C PiB to characterize global amyloid‐β(A) burden and F18 Flortaucipir (FTP) to quantify inferior temporal tau(T). Participants were dichotomized as A+/A‐ and T+/T‐ using previously described mixture model distribution cut‐points. Because FTP only became available mid‐study, we undertook two analytical approaches: 1) cox regression analysis with first PiB scan as time origin (n=342, follow‐up=6.10 years;range=1‐9) with tau treated as a time‐varying covariate (setting it to T‐ prior to the first FTP scan if T‐ and setting it to missing prior to first scan if T+) and 2) first FTP scan as time origin with tau treated as fixed at that time (n=242, follow‐up=5.12 years;range=1‐7). Participants were diagnosed annually by biomarker‐blinded case conference. Covariates included Demographics and E4(+/‐). Result In the larger sample (31 individuals diagnosed with MCI/dementia), A+ was associated with increased diagnostic risk (HR=12.43, 95%CI=4.89‐31.57). In a model that included T as time‐varying (but not A), T+ was associated with increased risk for diagnosis (HR=4.46, 95% CI=0.99,20.11, p=0.051). Including A in the model, A+ was associated with increased diagnostic risk (HR=5.30, 95%CI=1.29,21.72) and T+ additionally appeared to confer higher risk, though not statistically significant (HR=2.89, 95%CI=0.12,67.73). An interaction term was not significant (HR for A+T+ versus A+T‐=4.65,95%CI=0.28,77.79). In the smaller sample with tau (19 individuals diagnosed), T+ was also associated with greater risk for diagnosis (HR=3.61, 95%CI=1.38‐9.40). Older age (HR=1.09, 95%CI=1.02‐1.18) and E4+ (HR=5.40, 95%CI=1.96‐14.89) were contributory. Both A+ (HR=13.83, 95%CI=2.82‐67.81) and T+ (HR=2.75, 95%CI=1.05‐7.24) are associated with higher diagnostic risk when included in the same model. A+T+ was associated with higher risk(HR=2.59, 95%CI=0.98‐6.83,p=0.055) compared with A+T‐. Conclusion A+ in combination with T+, is a significant risk factor for clinical progression. These findings provide further encouragement that interrupting A among CN older adults may mitigate risk for clinical progression.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2201940-6
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