Derivation and utility of an A beta-PET pathology accumulation index to estimate A beta load

• Objective To evaluate a novel beta-amyloid (A beta)-PET-based quantitative measure (A beta accumulation index [A beta index]), including the assessment of its ability to discriminate between participants based on A beta status using visual read, CSF A beta(42)/A beta(40), and post-mortem neuritic plaque burden as standards of truth. Methods One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with A beta-PET: Swedish BioFINDER, n = 392, [F-18]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [F-18]florbetapir; and a phase 3 end-of-life study, n = 100, [F-18] flutemetamol. The relationships between A beta index and standardized uptake values ratios (SUVR) from A beta-PET were assessed. The diagnostic performances of A beta index and SUVR were compared with visual reads, CSF A beta(42)/A beta(40), and A beta histopathology used as reference standards. Results Strong associations were observed between A beta index and SUVR (R-2: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating A beta-positive from A beta-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF A beta(42)/A beta(40), and AUCs of 0.820 to 0.823 to detect abnormal A beta histopathology. Both measures also showed a similar distribution across postmortem-based A beta phases (based on anti-A beta 4G8 antibodies). Compared to models using visual read alone, the addition of the A beta index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal A beta histopathology. Conclusion The proposed A beta index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. A beta index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different A beta-PET tracers. Classification of evidence This study provides Class III evidence that the A beta accumulation index accurately differentiates A beta-positive from A beta-negative participants compared to A beta-PET visual reads, CSF A beta(42)/A beta(40), and A beta histopathology.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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