Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment

Abstract

Objective: The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease.

Methods: Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables.

Results: Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes.

Discussion: Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

Fig 1. Images representative of entorhinal volumetric and fiber tracking results.

Image demonstrating left entorhinal (in red on top panel) and ERC-RSC fibers (temporal cingulum) with entorhinal cortex and retrosplenial region ROIs in orange (bottom panel).

Fig 2. Control-based z scores of temporal and frontal-subcortical regions for PD-Well and PD-MI.

*Denotes group difference p<0.05. ERC/TICV = Left entorhinal volume/TICV, Temporal FA = Mean fractional anisotropy of the white matter of the left temporal lobe, Temporal Cingulum EW = Edge weight connectivity of the left temporal cingulum, Frontal thickness = Total mean frontal cortex thickness, Prefrontal FA = Total mean fractional anisotropy of frontal white matter anterior to the rostrum of the corpus callosum, Caudate/TICV = total caudate/TICV, Putamen/TICV = total putamen/TICV, Thalamus/TICV = total thalamus/TICV.