Objective: To assess the functional significance of hippocampal network dysfunction in Parkinson’s disease related amnestic mild cognitive impairment (PD aMCI) using high-resolution functional neuroimaging.

Background: Cognitive impairment is among the most frequent non-motor symptoms in PD and is associated with an increased risk of dementia. Memory is one of the earliest and most often affected cognitive domains in PD MCI. Hippocampal network dysfunction has been shown to play a key role in animal models of age-related memory impairment and in PD dementia with memory impairment. Recent studies in non-PD aMCI have demonstrated increased fMRI activation in the dentate gyrus/CA3 (DG/CA3) subregion of the hippocampus and have correlated this activation with memory impairment. This localized hippocampal subregion activation is considered a characteristic feature of the aMCI phase of Alzheimer’s disease (AD) and a predictor of cognitive decline. It remains unclear if DG/CA3 hyperactivity and associated memory deficits are specific to AD or if they also form the basis for PD aMCI.

Methods: To assess memory performance, neuropsychological evaluations were administered to 8 participants with PD aMCI and 10 age-matched healthy controls. Additionally, high-resolution fMRI methods were employed to evaluate hippocampal network function. A pattern separation task, designed to differentially tax the CA1 and DG/CA3 hippocampal subregions, was administered in the scanner.

Results: PD patients with aMCI made significantly fewer correct responses (30%) during the pattern separation task compared to controls (50%) (p<0.05). In addition, PD aMCI participants showed an area of task-related hyperactivity specific to the left DG/CA3 subregion of the hippocampus compared to controls.

Conclusions: Consistent with observations in non-PD aMCI, increased activation in the hippocampal DG/CA3 subregion is associated with impaired performance on the pattern separation task in PD aMCI. These findings suggest this hyperactivation signature may be a mechanism for memory dysfunction in both AD and PD.

References: Bakker, A., Kirwan, C. B., Miller, M., & Stark, C. E. (2008). Pattern separation in the human hippocampal CA3 and dentate gyrus. Science,319(5870), 1640-1642.

Leutgeb, J. K., Leutgeb, S., Moser, M. B., & Moser, E. I. (2007). Pattern separation in the dentate gyrus and CA3 of the hippocampus. science,315(5814), 961-966.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-hippocampal-activation-in-parkinsons-disease-related-amnestic-mild-cognitive-impairment/