title: Rivastigmine is associated with restoration of left frontal brain activity in Parkinson's disease.
abstract: The objective of this study was to investigate how acetylcholinesterase inhibitor (ChEI) treatment affects brain function in Parkinson's disease (PD). Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after 3 months of ChEI treatment and were compared with 15 age- and sex-matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low-frequency fluctuations. At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (eg, caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (eg, lateral prefrontal cortex), and episodic memory (eg, precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased posttreatment compared with baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared with controls, and rivastigmine is associated with performance-related normalization in the left frontal cortex function.
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, California, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Possin
authors.forename: Gail A
authors.initials: GA
authors.lastname: Kang
authors.forename: Christine
authors.initials: C
authors.lastname: Guo
authors.forename: Eric M
authors.initials: EM
authors.lastname: Fine
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Trujillo
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Racine
authors.forename: Reva
authors.initials: R
authors.lastname: Wilheim
authors.forename: Erica T
authors.initials: ET
authors.lastname: Johnson
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Witt
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
mesh_terms: D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003463:Cues; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects*; D007839:Functional Laterality; D019416:Head Movements / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D048448:Phenylcarbamates / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D020127:Recovery of Function; D000068836:Rivastigmine; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D000068836:Rivastigmine
keywords: acetylcholine; acetylcholinesterase inhibitors; attention; executive control; magnetic resonance imaging functional