Tiffini Voss, MD1; Ying Zhang, PhD1; Cyrille Sur, PhD1; James Kost, PhD1; Yi Mo, PhD1; Joyce Suhy, PhD2; Gregory Klein, PhD2; Jerome Barakos, MD3; Teresia Möller, PhD4; Benjamin Newton, PhD5; Lyn Harper Mozley, PhD1; Julie Chandler, PhD1; Yuki Mukai, MD1; Christopher Randolph, PhD, ABPP-CN6; and Michael Egan, MD1
1Merck & Co., Inc., Kenilworth, NJ, USA; 2Bioclinica, Inc., Newark, CA, USA; 3California Pacific Medical Center, San Francisco, CA, USA; 4GE Healthcare, Boston, MA, USA; 5GE Healthcare, Little Chalfont, United Kingdom; 6Loyola University Medical Center, Chicago, IL, USA
- The presence of amyloid is required for a diagnosis of Alzheimer's disease
- However, in prior work, amyloid burden does not always correlate with the severity of cognitive impairment, especially in more advanced disease (clinical dementia)
- We analyzed screening data from the APECS trial (MK8931-019, NCT#01953601) to evaluate, in amnestic mild cognitive impairment (MCI), whether regional amyloid positivity is associated with lower cognitive performance in cognitive domains relevant to that anatomic region
- To investigate gender differences age related changes of muscle and adipose tissue volume in the thigh.
- Propose a robust and automatic algorithm for the quantitative assessment of volume of thigh muscle, inter- and intra-muscular fat; Overcome the time-consuming and operator-dependent problems in traditional manual analysis, especially towards 3D datasets.
- Amyloid PET data and baseline cognitive performance were analyzed from the ongoing MK-8931-019 (APECS) trial of verubecestat
- Trial participants were screened using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index (DMI) ≤85 to define memory impairment; only those with memory impairment underwent PET
- PET positivity was determined by visual read in accordance with approved labelling. Six regions were examined in this exploratory analysis: frontal, parietal, temporal, cingulate, striatal, and precuneus
- Cognitive performance was assessed using five RBANS index scores: immediate memory, delayed memory, language, attention, and visuospatial/constructional
- For each anatomical region, the mean RBANS scores for PET negative vs positive were compared
- The impact of number of additional PET-positive regions on RBANS score was also assessed
- Of the 765 individuals analyzed, 556 (73%) were PET positive
- Baseline age, education, MMSE, and ADCS-ADL were similar between PET-positive and PET-negative individuals
- Within PET-positive individuals, 69% were positive for all six regions; 20% for 3–5 regions; 11% for 1 or 2 only. The frontal region was most often positive (94%), while temporal and striatal were least frequently positive (77%)
- Regardless of anatomic region studied, PET-positive individuals had worse performance on the immediate memory index (IMI) and DMI as compared to PET-negative individuals: eg, for frontal region, mean DMI difference 9.1, 95%CI (7.01–11.2); IMI difference 9.25, 95%CI (6.95–11.56)
- There were no nominal differences in attention, language, or visuospatial performance between PET-positive and PET-negative individuals, regardless of anatomic region
- For both immediate and delayed memory, scores tended to decline as the number of positive PET regions increased; this pattern was not observed for the other cognitive domains
- Immediate and delayed memory performance were lower among PET-positive individuals for all regions, with performance on these indices also declining as the number of amyloid-positive regions increased
- Otherwise, there was no clear relationship between domain-specific cognitive performance and regional amyloid burden
- This study was funded by Merck & Co., Inc.
- Tiffini Voss, Ying Zhang, Cyrille Sur, James Kost, Lyn Harper Mozley, Yuki Mukai, and Michael Egan are employees of Merck & Co., Inc., and own stock/stock options in Merck & Co., Inc.
- Yi Mo and Julie Chandler were previously employees of Merck and Co., Inc at the time the data were analyzed.