Validity of cingulate–precuneus–temporo-parietal hypometabolism for single-subject diagnosis of biomarker-proven atypical variants of Alzheimer’s Disease

• Published in: Journal of neurology Vol. 269; no. 8; pp. 4440 - 4451
• Main Authors: Isella, Valeria, Crivellaro, Cinzia, Formenti, Anna, Musarra, Monica, Pacella, Sara, Morzenti, Sabrina, Ferri, Francesca, Mapelli, Cristina, Gallivanone, Francesca, Guerra, Luca, Appollonio, Ildebrando, Ferrarese, Carlo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2022; Springer Nature B.V
• Subjects: Alzheimer's disease; Amyloidosis; Aphasia; Biomarkers; Cerebrospinal fluid; Cognitive ability; Cortex (parietal); Dementia disorders; Diagnosis; Medicine; Medicine & Public Health; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Original Communication; Patients; Phenotypes; Positron emission tomography; FDG-PET; Biomarkers; Alzheimer’s Disease; Brain metabolism; Dementia
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-022-11086-y

The aim of our study was to establish empirically to what extent reduced glucose uptake in the precuneus, posterior cingulate and/or temporo-parietal cortex (PCTP), which is thought to indicate brain amyloidosis in patients with dementia or MCI due to Alzheimer’s Disease (AD), permits to distinguish amyloid-positive from amyloid-negative patients with non-classical AD phenotypes at the single-case level. We enrolled 127 neurodegenerative patients with cognitive impairment and a positive (n. 63) or negative (n. 64) amyloid marker (cerebrospinal fluid or amy-PET). Three rating methods of FDG-PET scan were applied: purely qualitative visual interpretation of uptake images (VIUI), and visual reading assisted by a semi-automated and semi-quantitative tool: INLAB, provided by the Italian National Research Council, or Cortex ID Suite, marketed by GE Healthcare. Fourteen scans (11.0%) patients remained unclassified by VIUI or INLAB procedures, therefore, validity values were computed on the remaining 113 cases. The three rating approaches showed good total accuracy (77–78%), good to optimal sensitivity (81–93%), but poorer specificity (62–75%). VIUI showed the highest sensitivity and the lowest specificity, and also the highest proportion of unclassified cases. Cases with asymmetric temporo-parietal hypometabolism and a progressive aphasia or corticobasal clinical profile, in particular, tended to be rated as AD-like, even if biomarkers indicated non-amyloid pathology. Our findings provide formal support to the value of PCTP hypometabolism for single-level diagnosis of amyloid pathophysiology in atypical AD, but also highlight the risk of qualitative assessment to misclassify patients with non-AD PPA or CBS underpinned by asymmetric temporo-parietal hypometabolism.