Flortaucipir PET scan patterns correlate with risk for decline in AD, cognitive impairment

When examined with an FDA-approved, clinically relevant method, flortaucipir PET scans provided “valuable information” about risk for clinical decline in patients with Alzheimer’s disease and mild cognitive impairment, according to a study.

Researchers published the results in JAMA Neurology.

“Published studies to date have focused on quantitative analyses of flortaucipir PET scans, which is suitable for research purposes but could pose a challenge in clinical practice,” Ming Lu, MD, MPH, MS, of Avid Radiopharmaceuticals, and colleagues wrote. “Visual scan interpretation may enable broader clinical application and make flortaucipir more accessible to medical practitioners and, therefore, to patients.”

The FDA approved a clinically relevant visual interpretation method for detecting cortical tau deposition, according to Lu and colleagues, and an autopsy study confirmed its accuracy for this purpose. The research by Lu and colleagues examined the link between flortaucipir visual interpretation patterns and clinical decline at 18 months.

The analysis included participants from two prospective, open-label, longitudinal studies conducted from 2014 to 2019. All participants in both studies were diagnosed as clinically impaired, according to the results from Lu and colleagues.

In study 1, the researchers screened 298 patients and enrolled 160 who received a flortaucipir PET scan at baseline. In study 2, the researchers included 205 participants from the AMARANTH trial, which stopped following a futility analysis. Among 2,218 AMARANTH participants, 424 received a flortaucipir scan around the time of randomization, but 219 did not finish the 18-month clinical dementia rating (CDR) evaluation and were therefore excluded.

Lu and colleagues used the FDA-approved visual scan interpretation approach to characterize participants’ flortaucipir scans as being either an advanced or nonadvanced AD pattern. They calculated the CDR sum of box (CDR-SB) score as the primary clinical endpoint in both studies.

The final analysis included data from 364 participants (women, 48%; mean age, 71.8 years; advanced AD pattern, n = 240). Researchers assessed CDR-SB score, approximately 18 months after baseline; they defined clinically meaningful deterioration as an increase of 1 point or more in the CDR-SB.

At 18 months, the researchers found that 70% of patients with an advanced AD pattern (147/210) experienced a 1 point or greater increase in CDR-SB. Conversely, 46% of individuals with a nonadvanced AD pattern scan (48/105) experienced the same event (RR = 1.40; 95% CI, 1.11-1.76). The adjusted mean CDR-SB change was 2.28 points in the advanced AD pattern group and 0.98 points in the nonadvanced AD pattern group (P < .001). Additionally, the evaluation of other clinical endpoints and analyses of each individual study consistently demonstrated a greater risk for clinical decline that correlated with an advanced AD scan pattern, according to Lu and colleagues.

“... Data from 2 independent studies consistently demonstrated that participants with a flortaucipir advanced AD tau pattern are at a higher risk of clinically meaningful deterioration,” the researchers wrote. “Thus, flortaucipir PET, interpreted with a clinically applicable visual method, could provide helpful information regarding anticipated clinical decline in the management of patients being assessed for causes of cognitive impairment.”