Study: PET sheds light on neuropathology of Alzheimers

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Researchers continue to make headway in grasping the biological nature of Alzheimer’s disease, with a recent study discovering significant increases in the beta-amyloid uptake of florbetapir F18 as viewed on PET, published July 11 in the Archives of Neurology.

“Using positron emission tomography (PET) to image fibrillar amyloid has begun to have transformational effects on the scientific study, early detection, and tracking of Alzheimer disease (AD) and on the evaluation of amyloid-modifying treatments,” explained Adam S. Fleisher, MD, of Banner Alzheimer’s Institute in Phoenix, and co-authors.

Fleisher and colleagues pooled data from four trials, which used florbetapir-PET to visualize beta-amyloid burden. Overall, 210 participants were included from 31 different U.S. research sites. Eighty-two participants were cognitively healthy, while 60 presented with mild cognitive impairment. Sixty-eight participants had probable AD (met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria for probable AD and had an Mini-Mental State Examination score at screening in the range of 10 to 24).

The authors implemented two thresholds to determine whether participants’ mean cortical-to-whole-cerebellar florbetapir F18 standard uptake value ratios (SUVR) were consistent with either: levels associated with neuropathological AD; or florbetapir F18 values associated with the presence of identifiable cortical beta-amyloid above the level of healthy individuals who do not carry the APOE4 gene, who are highly unlikely to have cortical beta-amyloid plaques.

Mean cortical-to-whole cerebellar SUVRs were highest in the AD group (1.39), compared with the mild-cognitive impairment group (1.17) and the healthy group (1.05). The authors also observed a relationship between age and higher SUVR in the healthy group, an association that did not manifest in the AD and mild cognitive impairment cohorts.

These relationships weakened, but remained significant, after controlling for the effects of APOE4 on participants’ beta-amyloid burdens.

Based on the criteria for SUVRs associated with nueropathological AD or beta-amyloid levels above those of healthy non-APOE4 carriers, 81 percent of AD patients surpassed the neuropathological SUVR threshold (1.17), compared with 40 percent of participants with mild cognitive impairment and 21 percent of healthy subjects.

In comparison to the healthy cutoff for beta-amyloid SUVR, 85 percent of AD patients, 47 percent of individuals with mild cognitive impairment and 28 percent of healthy participants surpassed the 1.08 SUVR mark.

“These results robustly support the ability of florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI [mild cognitive impairment], and OHC [older healthy control] groups using both continuous and binary quantitative measures of amyloid burden,” wrote Fleisher and co-authors.

“By using florbetapir positivity cutoff thresholds that were based on patients with neuropathologically confirmed AD and low-risk young individuals, we introduce criteria to determine whether an image is consistent with amyloid levels associated with an intermediate-to-high likelihood of pathologic AD or with having any identifiable presence of cortical amyloid.”

The authors acknowledged the need for larger and less selective (e.g. more randomized) studies to better determine the role of florbetapir-PET in diagnosing AD.

“[O]ur analysis provides additional support for the emerging role of florbetapir-PET imaging in the assessment of fibrillar beta-amyloid burden and underscores the need for standardization of definitions for positive amyloid scans,” the authors concluded.