Non‐AD pathologies, as measured using a mismatch index between regional brain metabolism and tau PET signal, are associated with age, sex, and amyloid burden.

Abstract

AbstractBackgroundBrain hypometabolism in the absence of tauopathy may indicate the presence of non‐AD pathologies. We aimed to investigate the mismatch between regional tau pathology and brain metabolism to characterize the profile of patients suspected to have co‐pathologies.MethodSixty‐one clinically impaired patients, attending the Memory Clinic, performed both a [18F]‐Fluorodeoxyglucose‐PET to assess brain metabolism and a [18F]‐MK6240 Tau‐PET to estimate tau burden. To compare these images, we normalized them using data from clinically normal older adults (n = 30), resulting in FDG and tau z‐scores for 74 FreeSurfer‐defined regions. We computed intra‐subject correlation coefficients between tau and FDG data as a mismatch index between tau and metabolism. We then compared FDG and tau z‐scores using intra‐individual paired sampled t‐tests and identified patients with hypometabolism exceeding tau pathology (suspecting co‐pathologies). To increase sensitivity, the same analysis was repeated using temporal regions only. We finally evaluated demographics, cognition, and amyloid burden in the group of patients with suspected co‐pathologies.ResultsIn the entire cohort, the intra‐subject FDG‐Tau correlation was significantly negative in the temporal lobe (r = ‐0.27, p<0.05), but not in the entire neocortex (r = ‐0.11), demonstrating closer association between modalities in the temporal lobe, and greater mismatch in the other regions. Twenty‐five (41%) patients had significantly greater FDG z‐scores than tau z‐scores, including thirteen (21%) with greater hypometabolism than tau pathology in the temporal lobe. These patients were older and more frequently male than patients with greater tau pathology; those with a temporal mismatch also had lower amyloid pathology (Table 1). Older ages and better cognition were associated with the mismatch index in the entire neocortex (r = 0.25/0.49, p<0.05); in addition, lower amyloid burden was associated with the temporal mismatch index (r = 0.27, p<0.05, Fig.1).ConclusionPatients with greater temporal hypometabolism than tau deposition are older, more frequently males, and have lower amyloid burden than patients with greater temporal tau deposition. These patients are suspected to have temporal non‐AD pathologies.