ABSTRACT
INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment. METHODS: Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers. RESULTS: Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE ε4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings. DISCUSSION: Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early-stage changes in APOE ε4 carriers before symptoms of mild cognitive impairment are present. HIGHLIGHTS: Graph theory connectivity detects preclinical hippocampal changes in APOE ε4 carriers. The AD disconnection hypothesis was supported in unimpaired APOE ε4 carriers. Hippocampal dysfunction starts asymmetrically on the left.
Subject(s)
Alzheimer Disease , Apolipoprotein E4 , Humans , Apolipoprotein E4/genetics , Heterozygote , Hippocampus/pathology , Memory , Memory Disorders/diagnostic imaging , Memory Disorders/genetics , Magnetic Resonance Imaging , Alzheimer Disease/pathology , Neuropsychological TestsABSTRACT
OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for motor symptoms of Parkinson's disease; however, there is conflicting literature about the effect of DBS on cognitive function. The authors conducted a historical cohort study involving patients with Parkinson's disease who underwent DBS of the globus pallidus pars interna (GPi; N=12) or subthalamic nucleus (STN; N=17). METHODS: The authors investigated differences in four neuropsychological test scores at 6 months post-DBS (follow-up) as compared with baseline (i.e., Boston Naming Test, WAIS Verbal Comprehension Index [WAIS-VCI], Working Memory Index [WAIS-WMI], and Processing Speed Index [WAIS-PSI]). RESULTS: GPi DBS patients showed no difference between baseline and follow-up on any neuropsychological test. STN DBS patients had lower scores indicating decreased performance at follow-up as compared with baseline on WAIS-PSI (mean [SD], 91.47 [10.42] versus 81.65 [12.03]; p=0.03). There was a significant (p=0.008) difference between the change in baseline to follow-up scores on the WAIS-VCI for the STN DBS and GPi DBS groups (i.e., STN DBS patients scored lower at the 6-month follow-up compared with baseline, whereas GPi DBS patients scored higher). CONCLUSIONS: GPi may be a preferred target for DBS in patients with Parkinson's disease when considering cognitive outcomes.