Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters

Hippocampal subregional volume changes in elders classified using positron emission tomography‐based Alzheimer's biomarkers of β‐amyloid deposition and neurodegeneration

“…In our (N)+ subjects, between‐group volume differences in the CA1 (conceivably related to tau pathology) surpassed the p < 0.05 threshold of statistical significance only when A−(N)+ subjects (non‐AD pathologic change) were added to the A+(N)+ subsample, and it is possible that some of the A−(N)+ cases might present tau pathology in the absence of Aβ deposition (Jack et al., 2018), possibly in interaction with other types of pathology such as transactive response DNA‐binding protein of 43 kDa (TDP‐43) proteinopathy (Nelson et al., 2019) or abnormalities in alpha‐synuclein (Teravskis et al., 2018). In our previous paper describing individual [ 18 F]FDG‐PET regional metabolic patterns in the present sample, we reported the presence of exclusive temporal lobe hypometabolism in some A−(N)+ subjects (Coutinho et al., 2020). This supports the idea that subjects with conditions such as primary age‐related tauopathy (PART; Jicha & Nelson, 2019) or limbic‐predominant age‐related TDP‐43 encephalopathy (LATE; Nelson et al., 2019) may have been included in our A−(N)+ group, thus contributing to a tau‐driven atrophy of specific parts of the hippocampus, such as the CA1, and consequently localized hypometabolism.…”

“…A scan was rated as “negative” when there was a clear separation between GM and WM, with strong WM uptake and no significant GM uptake. This visual method of analysis has been validated for different amyloid tracers (Camus et al., 2012; Clark et al., 2012; Yamane et al., 2017), and was carried out with the help of a 3D‐SSP semi‐quantitative method designed for the clinical analysis of brain [ 11 C]PIB‐PET (Cortex ID Suite, GE healthcare) and a standard uptake value ratio (SUVr) of the cortical areas normalized for the cerebellar GM (cutoff of 1.42 as criteria for positivity; Coutinho et al., 2020; Jack et al., 2017).…”

“…The protocol used for the classification of individuals as N+ or N− was described previously (Coutinho et al., 2020). In brief, the two board certified nuclear medicine physicians cited above consensually rated the exams as “positive” ((N)+) or “negative” ((N)−) based on visual interpretation assisted by the 3D‐SSP semi‐quantitative software (Cortex ID Suite, GE healthcare) as proposed in previous studies (Minoshima et al., 1995; Mosconi et al., 2008).…”

“…After the categorical classification of each individual as A+ or A− using [ 11 C]PIB‐PET and (N)+ or (N)− using [ 18 F]FDG‐PET, we combined the results of both categories to classify each individual using a modified “A(N) staging” (rather than the complete AT(N) staging, as the T variable was not available) according to the 2018 NIA‐AA research framework (Jack et al., 2018), as previously described (Coutinho et al., 2020).…”

“…Consistent findings of reduced volumes of specific hippocampal subregions in subjects with clinical diagnosis of aMCI or probable AD have been reported (Broadhouse et al, 2019;Lim et al, 2013;Mueller et al, 2010), but there is still a lack of neuroimaging studies investigating volumetric changes in separate hippocampal subfields across distinct AD categories defined according to the biologically based principles of the NIA-AA research framework (Jack et al, 2018). Such studies are important to verify if hippocampal subfield volume (HSV) deficits are detect- We recently investigated a sample of elderly subjects (including patients with mild dementia clinically compatible with AD, subjects with aMCI and cognitively unimpaired elderlies), and described a PET-based classification of those individuals into subgroups according to the presence of Aβ positivity (A+; based on cortical [ 11 C]PIB-PET uptake) and neurodegeneration ((N)+; according to brain metabolic reductions detected by [ 18 F]FDG-PET), following the principles of the NIA-AA research framework (Coutinho et al, 2020). In the present study, we report MRI-based volumetric measurements of hippocampal subfields in the same sample, with comparisons carried out between the four categories defined according to the A(N) classification.…”