Multimodal magnetic resonance imaging investigation of basal forebrain damage and cognitive deficits in Parkinson's disease

Background Cognitive deficits in Parkinson's disease (PD) may result from damage in the cortex as well as in the dopaminergic, noradrenergic, and cholinergic inputs to the cortex. Cholinergic inputs to the cortex mainly originate from the basal forebrain and are clustered in several regions, called Ch1 to Ch4, that project to the hippocampus (Ch1-2), the olfactory bulb (Ch3), and the cortex and amygdala (Ch4). Objective We investigated changes in basal forebrain and their role in cognitive deficits in PD. Methods We studied 52 nondemented patients with PD (Hoehn & Yahr 1-2) and 25 age-matched healthy controls using diffusion and resting state functional MRI. Results PD patients had a loss of structural integrity within the Ch1-2 and Ch3-4 nuclei of the basal forebrain as well as in the fornix. Tractography showed that the probability of anatomical connection was decreased in PD between Ch3-4 and the associative prefrontal cortex, occipital cortex, and peri-insular regions. There was a reduction in functional connectivity between Ch1-2 and the bilateral hippocampi and parahippocampal gyri, the left middle and superior temporal gyri, and the left fusiform gyrus and between Ch3-4 and the right inferior frontal gyrus and the right and left thalamus. In Ch1-2, loss of structural integrity and connectivity correlated with scores at the memory tests, whereas changes in Ch3-4 correlated with scores of global cognition and executive functions. Conclusion This study highlights the association between deficits of different cholinergic nuclei of the basal forebrain and the extent of cognitive impairments in nondemented PD patients. (c) 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.