Caudate-anchored cognitive connectivity pursuant to orthostatic hypotension in early Parkinson's disease

Abstract

¹⁸F-Florbetaben is a tracer used to evaluate the metabolic activity of and amyloid accumulation in the brain when measured in early- and late-phase, respectively. The metabolism of neural substrates could be viewed as a network and might be an important factor in cognition. Orthostatic hypotension (OH) might play an indirect moderating role in cognition, and its latent influence could modify the inherent cognitive network. This study aimed to identify changes of cognitive connectivity according to orthostatic stress in patients with early Parkinson's disease (PD). This study included 104 early PD patients who were evaluated with a head-up tilt-test and¹⁸F-Florbetaben positron emission tomography (PET). Cognition was assessed with a comprehensive neuropsychological battery that gauged attention/working memory, language, visuospatial, memory, and executive functions. PET images were analyzed visually for amyloid deposits, and early-phase images were normalized to obtain standardized uptake ratios (SUVRs) of pre-specified subregions relevant to specific cognitive domains. The caudate nucleus was referenced and paired to these pre-specified regions. The correlations between SUVRs of these regions were assessed and stratified according to presence of orthostatic hypotension. Among the patients studied, 22 (21.2%) participants had orthostatic hypotension. Nineteen patients (18.3%) were positive for amyloid-β accumulation upon visual analysis. Moderate correlations between the caudate and pre-specified subregions were observed (Spearman's rho, range [0.331-0.545]). Cognition did not differ, but the patterns of correlation were altered when the disease was stratified by presence of orthostatic stress. In conclusion, cognition in early PD responds to hemodynamic stress by adapting its neural connections between regions relevant to cognitive functions.

Figure 1

The Spearman correlation coefficients of the entire population (a), PD No-OH (b) and PD + OH (c) are expressed as the edges between the caudate and the ROIs. The degree of correlation is expressed with color; the brighter is the connection, the stronger it is. (a) In the analysis of all patients studied, the caudate nucleus maintained a moderate degree of association with the prefrontal areas; insula; hippocampus; parahippocampus; posterior cingulate gyrus; lingual gyrus; superior/inferior parietal gyrus; and the supramarginal, angular, superior temporal, and temporal pole areas. (b) In PD No-OH, the caudate-refenced associations with the dorsolateral and medial superior frontal, middle/inferior frontal gyrus, insula, hippocampus, inferior parietal gyrus, supramarginal gyrus, and superior temporal gyrus remained significant. However, the number of significant connections was reduced compared to the whole population, and degrees of correlation remained moderate. (c) PD + OH patients manifested different traits. Most of the observed connections of the left caudate nucleus lost their significance, except the correlation with the left lingual gyrus. A few links between the right caudate and right inferior frontal gyrus, insula, and posterior cingulate gyrus remained significant. Of note, the strength of the remaining connections increased. The figures were made with BrainNET Viewer, a graphical user interface (version 1.7; http//www.nitrc.org/projects/bnv).