Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity

Autor: David A. Loewenstein, Shanna L. Burke, De Kosky St, Michael Marsiske, Gabriel Lizarraga, C. Robayo, Maria T. Greig-Custo, Ranjan Duara, Nilufer Ertekin-Taner, Malek Adjouadi, Monica Rosselli, David E. Vaillancourt, S. De Santi, Yat Fung Shea, A. Ollarves, Raquel Behar, Todd E. Golde, Kevin Hanson, Warren W. Barker, Ailyn Penate
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Oncology
Apolipoprotein E
Male
Apolipoprotein E4
Hispanic
lcsh:RC346-429
0302 clinical medicine
Cognition
Genotype
Stilbenes
SUVR
Aged
80 and over
Aniline Compounds
Threshold
05 social sciences
Age Factors
Regular Article
Hispanic or Latino
Middle Aged
Neurology
lcsh:R858-859.7
Female
APOE
medicine.medical_specialty
Amyloid
Cognitive Neuroscience
Standardized uptake value
Neuroimaging
lcsh:Computer applications to medicine. Medical informatics
Sensitivity and Specificity
050105 experimental psychology
03 medical and health sciences
Sex Factors
Internal medicine
mental disorders
medicine
Dementia
Humans
0501 psychology and cognitive sciences
Radiology
Nuclear Medicine and imaging
Cognitive Dysfunction
Florbetaben
lcsh:Neurology. Diseases of the nervous system
Aged
Amyloid beta-Peptides
business.industry
Gold standard (test)
medicine.disease
Positron-Emission Tomography
Neurology (clinical)
business
030217 neurology & neurosurgery
Zdroj: NeuroImage: Clinical, Vol 22, Iss, Pp-(2019)
NeuroImage : Clinical
ISSN: 2213-1582
Popis: The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.
Highlights • Demographic factors did not affect the threshold for amyloid positivity. • Cognitive status did not affect this threshold for amyloid positivity. • APOE4 carriers had a higher threshold for amyloid positivity than non-carriers. • Among APOE4 carriers, non-Hispanics had higher amyloid load than non- Hispanics. • There was a continuous relationship between amyloid load and cognitive status.
Databáze: OpenAIRE
Externí odkaz: