The hippocampal sparing subtype of Alzheimer’s disease assessed in neuropathology and in vivo tau positron emission tomography: a systematic review

Table 1 Cut points for the determination of abnormal levels of flortaucipir uptake

Reference	Referred to as in our current study	Criterion	Region/s	Cut point	Data source
Jack et al. [14, 16]	‘Accuracy-based cut point’	Accuracy based on age-matched clinically normal versus amyloid-positive cognitively impaired individuals from the MCSA	Meta-ROI including entorhinal, amygdala, parahippocampal, fusiform, inferior temporal, and middle temporal ROIs	≥ 1.33	MCSA
Byun et al. [15]	‘1SD cut point’	Flortaucipir uptake + 1SD from amyloid-negative cognitively unimpaired individuals from ADNI	Hippocampus Entorhinal cortex	≥ 2.79 ≥ 3.73	ADNI
Jack et al. [16]	‘10% cut point’	Sensitivity (10th percentile flortaucipir uptake) based on amyloid-positive cognitively impaired study participants from ADNI	Hippocampus Entorhinal cortex	≥ 2.75 ≥ 3.83	ADNI
Schöll et al. [18]	‘Schöll cut point’	Conditional inference tree analysis to classify individuals into Braak stage I/II	Transentorhinal, hippocampus, and entorhinal cortex	≥ 1.40	BACS and UCSF-MAC
Maass et al. [19]	‘Maass cut point’	Conditional inference tree analysis to classify individuals into Braak stage I/II	Transentorhinal, hippocampus, and entorhinal cortex	≥ 1.13	BACS and UCSF-MAC

The methods for determination of abnormal levels of flortaucipir uptake are different (criterion column), and there is also additional methodological variation across the original studies. Partial volume correction was applied in our analysis of ADNI data and all the original studies except for the ‘accuracy-based cut point’, although borderline voxels were discarded by the authors.^14,16 The meta-ROI implemented in the ‘accuracy-based cut point’ includes amygdala, entorhinal cortex, fusiform, parahippocampal, and inferior temporal and middle temporal gyri. Hence, the meta-ROI does not include any of the regions used for subtyping in Murray et al. [7] i.e. superior temporal, middle frontal, and inferior parietal gyri. MCSA Mayo Clinic Study of Aging, BACS Berkeley Aging Cohort Study, UCSF-MAC University of California San Francisco—Memory and Aging Center, ADNI Alzheimer's Disease Neuroimaging Initiative, ROI region of interest, SD standard deviation, pc percentile

ISSN: 2051-5960