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

Abstract

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.

Atypical forms of Alzheimer's disease: patients not to forget

“…For example, in atypical AD patients (PCA & lvPPA), the influence of APOE ε4 on both the patterns of neurodegeneration and tau deposition has been established, with individuals carrying this genetic variant displaying more medial temporal involvement at baseline, although there is evidence that noncarriers may catch up in their rate of progression over time [33 ▪ ]. While there have been many group-based studies, it is also important to investigate single-subject markers that can be used in clinical settings, where borderline profiles can be observed [34,35].…”

Dissecting the Many Faces of Frontotemporal Dementia: An Imaging Perspective

“…The distribution of atrophy and hypometabolism helps in differentiating FTD from Alzheimer’s disease (AD) [ 25 , 29 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”