Hypometabolism in Brain of Cognitively Normal Patients with Depressive Symptoms is Accompanied by Atrophy-Related Partial Volume Effects

Late life depression (LLD) even in subsyndromal stages shows high conversion rates from cognitively normal (CN) to mild cognitive impairment (MCI). Results of [18F]-fluorodesoxyglucose positron-emission-tomography (FDG-PET) were inconsistent in LLD patients, whereas atrophy was repeatedly described. Therefore, we set out to investigate FDG metabolism and the effect of atrophy correction (PVEC) in geriatric CN patients with depressive symptoms. 21 CN subjects with positive item for the depression category (DEP) in the Neuropsychiatric-Inventory-Questionnaire and 29 CN subjects with an absent depression item (NON-DEP) were selected from the ADNI cohort. FDG-PETs were analyzed in individual PET space using volumes-of-interest (VOI) and statistical-parametric-mapping (SPM) approaches. VOI- and MRI-based PVEC were applied to PET data. DEP subjects showed significant hypometabolism in fronto-temporal cortices and the posterior cingulate cortex (PCC) when contrasted against NON-DEP in uncorrected data. Both in VOI- and SPM-based approaches PVEC eliminated significance in PCC, while fronto-temporal regions remained significant or even attained significance such as in case of the left amygdala. Subsyndromally depressed CN subjects had decreased FDG metabolism in mood-related brain regions, which may be relevant to their elevated risk for conversion from CN to MCI. Methodological advances in PET analyses should be considered in future studies as PVEC relevantly changed results of FDG-PET for detecting apparent metabolic differences between DEP and NON-DEP subjects. Furthermore, VOI-based analyses in individual PET space will allow a more accurate consideration of variability in anatomy, especially in subcortical regions.