Identification and validation of Alzheimer's disease-related metabolic brain pattern in biomarker confirmed Alzheimer's dementia patients.

ABSTRACT

Metabolic brain biomarkers have been incorporated in various diagnostic guidelines of neurodegenerative diseases, recently. To improve their diagnostic accuracy a biologically and clinically homogeneous sample is needed for their identification. Alzheimer's disease-related pattern (ADRP) has been identified previously in cohorts of clinically diagnosed patients with dementia due to Alzheimer's disease (AD), meaning that its diagnostic accuracy might have been reduced due to common clinical misdiagnosis. In our study, we aimed to identify ADRP in a cohort of AD patients with CSF confirmed diagnosis, validate it in large out-of-sample cohorts and explore its relationship with patients' clinical status. For identification we analyzed 2-[18F]FDG PET brain scans of 20 AD patients and 20 normal controls (NCs). For validation, 2-[18F]FDG PET scans from 261 individuals with AD, behavioral variant of frontotemporal dementia, mild cognitive impairment and NC were analyzed. We identified an ADRP that is characterized by relatively reduced metabolic activity in temporoparietal cortices, posterior cingulate and precuneus which co-varied with relatively increased metabolic activity in the cerebellum. ADRP expression significantly differentiated AD from NC (AUC = 0.95) and other dementia types (AUC = 0.76-0.85) and its expression correlated with clinical measures of global cognition and neuropsychological indices in all cohorts.