We sought to determine if Parkinson's disease (PD) with mild cognitive impairment (MCI) is associated with a greater SERIAL-ORDER (mental manipulation) than ANY-ORDER (auditory span, storage) deficit in working memory (WM). We investigated WM combining neuropsychological measures with the study of brain functional connectivity. A cohort of 160 patients with idiopathic PD, classified as PD-MCI (n = 87) or PD with normal cognition (PD-NC; n = 73), and 70 matched healthy controls were studied. Verbal WM was assessed with the Backward Digit Span Task (BDT; Lamar et al., 2007, Neuropsychologia, 45, 245), measuring SERIAL-ORDER and ANY-ORDER recall. Resting-state MRI data were collected for 15 PD-MCI, 15 PD-NC and 30 controls. Hypothesis-driven seed-based functional connectivity of the dorsolateral prefrontal cortex (DLPFC) was compared between the three groups and correlated with BDT performance. We found the main effect of the test (impairment in SERIAL ORDER > ANY ORDER) and group ((NC = PD-NC) > PD-MCI) in BDT performance that was even more pronounced in SERIAL ORDER when controlling for ANY ORDER variability but not vice versa. Furthermore, PD-MCI compared to other groups were characterized by the functional disconnection between the bilateral DLPFC and the cerebellum. In functional correlations, DLPFC connectivity was positively related to both SERIAL- and ANY-ORDER performance. In conclusion, PD-MCI patients evidenced greater SERIAL-ORDER (manipulation and cognitive control) than ANY-ORDER (storage) working memory impairment than PD-NC and controls with a disrupted DLPFC resting-state connectivity that was also related to the verbal WM performance.

Clinic for Cognitive Neurology University Clinic Leipzig Germany

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine General University Hospital Charles University Prague Czech Republic

FTLD Consortium Ulm Germany

Max Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany

Rush Alzheimer's Disease Center Department of Psychiatry and Behavioral Sciences Rush University Medical Center Chicago Illinois USA

School of Osteopathic Medicine New Jersey Institute for Successful Aging Departments of Geriatric Gerontology and Psychology Rowan University Stratford New Jersey USA

School of Psychology University of Western Australia Crawley Western Australia Australia

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