Advanced Alzheimer Flortaucipir Pattern Associated With Increased Risk of Clinical Progression

March 5, 2021
Marco Meglio
Marco Meglio

Marco Meglio, Associate Editor for NeurologyLive, has been with the team since October 2019. Follow him on Twitter @marcomeglio1 or email him at

At 18-month follow-up, 70% of those with an advanced Alzheimer disease pattern had 1 point or more increase in CDR-SB, an event predefined as clinically meaningful deterioration.

Results from 2 prospective, open-label, longitudinal, phase 3 studies demonstrated that patients with an advanced Alzheimer disease (AD) tau pattern, measured by flortaucipir (Tauvid), are at a higher risk of clinically meaningful deterioration.

The researchers also found that interpreting flortaucipir positron emission tomography (PET) scans using an FDA-approved, clinically applicable visual interpretation method could provide helpful information regarding anticipated clinical decline in the management of patients being assessed for causes of cognitive impairment. Senior author Mark A. Mintun, MD, president, Avid Radiopharmaceuticals, and colleagues collected data on 364 cognitively impaired participants with a range of demographic characteristics and clinical presentations similar to patients seen in a clinical practice setting over 18 months.

Pooling Study 1 (NCT02016560) and Study 2 (NCT03901105) data, 240 participants had an advanced and 124 participants had a nonadvanced AD flortaucipir scan pattern. At the end of the study period, 70% of the advanced group had a clinical dementia rating (CDR) sum of box (CDR-SB) score increase of 1 point or more, compared to 46% of those with a nonadvanced AD pattern scan experiencing the same event (risk ratio [RR], 1.40; 95% CI, 1.11-1.76; P = .005). Overall, the adjusted mean CDR-SB changes were 2.28 and 0.98 for advanced and nonadvanced AD pattern groups, respectively (P <.001).

In both studies, participants’ clinical progression was measured with the CDR scale, including both CDR-SB and CDR-Global, the Mini Mental State Examination (MMSE), 11-item version of the Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog11), and Functional Activities Questionnaire (FAQ).

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In addition to the aforementioned changes in CDR-SB, researchers also saw similar statistically significant RRs for the other assessments. At the 18-month follow-up adjusted mean changes were –4.13 vs 1.27 (P<.001) for MMSE, 6.15 vs 2.10 (P<.001) for FAQ, and 6.40 vs 2.30 (P<.001) for advanced compared to nonadvanced AD patterns, respectively.

Among the 3 different scan patterns, the moderate AD pattern occurred the least frequently in both studies. Mintun and colleagues also found an association of clinical progression by scan patterns (advanced > moderate > negative AD pattern) after pooling data.

The inter-reader consistency for flortaucipir scan visual interpretation was high in both Study 1 and 2 (94.5% and 91.4% agreement rate), resulting in homogenous findings similar to that observed for majority reads. Hazard ratio (HR) values from the analyses of CDR-SB event ranged from 1.49 to 1.70 in Study 1, and the corresponding RR values ranged from 1.25 to 1.46 in Study 2.

The researchers also found that impairment severity level at baseline was positively associated with participants’ clinical progression. Regardless of tau status, the study population had CDR-SB deteriorate from 0.51 to 3.61 points ranging from the healthiest to the most impaired MMSE baseline level.

Study 1 had a total of 159 participants that had flortaucipir scans that passed quality control. Of them, 64% were amyloid-beta positive (Aß+), 41% were apolipoprotein E (APOE) ε4 carriers, and 78 (49%) had an advanced, 11 (7%) had a moderate, and 70 (44%) had a negative AD pattern. Among Study 1 participants, compared with the Aß- group, the Aß+/advanced AD pattern group showed significantly greater CDR-SB progression (mean change, 1.99 vs 0.72; P = .02), whereas the Aß+/nonadvanced group progressed similarly to the Aß- group (0.86 vs 0.72; P = .84).

In Study 2, otherwise known as AMARANTH, all participants were Aß+ per enrollment criteria, and 69% were APOE ε4 carriers. A total of 162 (79%) participants had an advanced AD pattern, 15 (7.3%) had a moderate AD pattern, and 28 (13.7%) had a negative AD pattern.

Lu M, Pontecorvo MJ, Devous MD, et al. Aggregated tau measured by visual interpretation of flortaucipir positron emission tomography and the associated risk of clinical progression of mild cognitive impairment and Alzheimer disease. JAMA Neurol. Published online February 15, 2021. doi: 10.1001/jamaneurol.2020.5505