Disclosures: Ossenkoppele reports no relevant financial disclosures. Please see the full study for all other authors' relevant financial disclosures.
June 29, 2021
3 min read
Save

Tau PET imaging represents 'promising tool' for predicting changes in cognitive status

Disclosures: Ossenkoppele reports no relevant financial disclosures. Please see the full study for all other authors' relevant financial disclosures.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Tau PET imaging successfully predicted longitudinal changes in cognition among individuals with varying degrees of cognitive function, according to results from a prognostic study published in JAMA Neurology.

The findings highlighted tau PET as a “promising tool” for predicting cognitive change that is superior to both amyloid PET and MRI, the researchers noted. As a result, this imaging approach may support the “prognostic process” in both preclinical and prodromal Alzheimer’s disease.

“Despite the development of several biomarkers for neurodegeneration and AD pathology in past decades, accurately predicting rates of cognitive decline in individuals with AD remains challenging,” Rik Ossenkoppele, PhD, and colleagues wrote. “Given the strong links between tau pathology and key correlates of cognition (eg, neuronal loss and synaptic dysfunction) observed in vitro and at autopsy, in vivo information about the magnitude of cerebral tau pathology might improve the prediction of future cognitive decline.”

Ossenkoppele, a researcher and associate senior lecturer in clinical memory research at Lund University in Sweden, and colleagues noted that increased tau PET levels at baseline were recently linked to greater cognitive decline over time, although “most studies had relatively modest sample sizes, lacked a replication cohort, and/or focused on one stage of the AD clinical continuum.” They aimed, in this prospective, longitudinal, multicenter study, to analyze the prognostic accuracy of baseline fluorine 18-flortaucipir and tau PET among individuals across the AD clinical spectrum and to complete a head-to-head comparison with MRI and amyloid PET markers.

The researchers pooled data from eight patient cohorts in South Korea, Sweden and the United States between June 1, 2014, and February 28, 2021, with a mean follow-up period of 1.9 years. They included 1,431 participants from memory clinics, clinical trials or cohort studies (mean age, 71.2 years; 52.5% men).

The patient cohorts included those with no cognitive impairment (n = 673; amyloid beta positivity, n = 253 [37.6%]), those with mild cognitive impairment (n = 443; amyloid beta positivity, n = 271 [61.2%]) and those with a clinical diagnosis of AD dementia (n = 315; amyloid beta positivity, n = 315 [100%]). Exposures included fluorine 18-flortaucipir PET in the discovery cohort (n = 1,135) or tau PET in the replication cohort (n = 296), T1-weighted MRI (n = 1,431) and amyloid PET (n = 1,329) at baseline, as well as repeated evaluations with the Mini-Mental State Examination.

Ossenkoppele and colleagues found that fluorine 18-flortaucipir PET indicated longitudinal changes in the Mini-Mental State Examination, with effect sizes that were more robust than for AD-signature cortical thickness and amyloid PET among all participants (R2 = 0.35 for tau PET vs. 0.24 for MRI vs. 0.17 for amyloid PET; P < .001, bootstrapped for difference) in the amyloid beta-positive mild cognitive impairment group (R2 = 0.25 for tau PET vs. 0.15 for MRI vs. 0.07 for amyloid PET; P < .001, bootstrapped for difference) and in the amyloid-beta-positive cognitively unimpaired group (R2 = 0.16 for tau PET vs. 0.08 for MRI vs. 0.08 for amyloid PET; P < .001, bootstrapped for difference). The researchers replicated these results in the tau PET cohort, according to the study results.

The researchers also demonstrated that MRI mediated the relationship between fluorine 18-flortaucipir PET and the Mini-Mental State Examination in the cohorts with AD dementia (33.4% [95% CI, 15.5%-60%] of the total effect) and amyloid beta-positive mild cognitive impairment (13.6% [95% CI, 0%-28%] of the total effect), but not in the amyloid beta-positive cognitively unimpaired group. Age (P = .02), but not sex or APOE genotype, changed the relationship between baseline fluorine 18-flortaucipir PET and cognitive change, in that older individuals demonstrated more accelerated cognitive decline at similar tau PET levels.

“Tau PET outperformed established MRI and amyloid PET markers in a head-to-head comparison, especially in the [amyloid beta]-positive [mild cognitive impairment] and [amyloid beta]-positive [cognitively unimpaired] groups,” Ossenkoppele and colleagues wrote. “Our findings suggest that although tau PET as a diagnostic marker is most valuable at the dementia stage of AD, the optimal time window for tau PET as a prognostic marker is during the prodromal and preclinical stages of AD.”