Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment

BACKGROUND AND PURPOSE Diagnosis of Parkinson's disease (PD) cognitive impairment at early stages is challenging compared to the stage of PD dementia where functional impairment is apparent and easily diagnosed. Hence, to evaluate potential early stage cognitive biomarkers, we assessed frontal lobe metabolic alterations using in vivo multi-voxel proton magnetic resonance spectroscopic imaging (1H-MRSI). METHOD Frontal metabolism was studied in patients with PD with normal cognition (PD-CN) (n = 26), with cognitive impairment (PD-CI) (n = 27), and healthy controls (HC) (n = 30) using a single slice (two-dimensional) 1H-MRSI at 3 T. The acquired spectra were post-processed distinctly for voxels corresponding to the bilateral middle/superior frontal gray matter (GM) and frontal white matter (WM) regions (delineated employing neuromorphometrics atlas) using the LC-Model software. RESULT Significant (post hoc p < 0.016) reduction in the concentration of N-acetyl aspartate (NAA) in the middle and superior frontal GMs and total choline (tCho) and total creatine (tCr) in the frontal WM was observed in PD-CI compared to PD-CN and HC, while that in HC and PD-CN groups were comparable. The NAA and tCr/tCho metabolite concentrations showed significant (p < 0.05) positive correlations with cognitive test scores in the frontal GM and WM, respectively. The receiver operating curve (ROC) analysis revealed significant (p < 0.05) "area under curve" for NAA/tNAA in the frontal GM and tCho in the frontal WM. CONCLUSION The frontal metabolic profile is altered in cognitively impaired PD compared with cognitively normal PD. Neuronal function loss (NAA), altered energy metabolism (Cr), and cholinergic (Cho) neural transmission are implicated in PD cognitive pathology. Frontal neuro-metabolism may promisingly serve as PD cognitive biomarker.