Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI.

Shankar Tumati,Sander Martens,Peter P De Deyn,Fransje E Reesink,Esther M Opmeer,André Aleman,Jan-Bernard C Marsman

doi:10.3389/fnagi.2018.00106

Abstract

Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI) and is associated with an increased risk of progression to Alzheimer’s disease (AD). The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy (1H-MRS). Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (DACC), right dorsolateral prefrontal cortex (DLPFC), and right temporo-parietal cortex (TPC). Apathy was measured with the Apathy Evaluation Scale (AES). Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA) were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI) in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA)/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx) levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

Highlights

In amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) dementia, apathy is associated with an increased risk for disease progression and poor functional outcomes (Boyle et al, 2003; Teng et al, 2007; Lanctôt et al, 2016)
The Geriatric Depression Scale (GDS) non-apathy subscore, denoting depression independent of apathy, was significantly higher in the patient group compared to controls
The Apathy Evaluation Scale (AES) score was significantly correlated with the GDS total score (r = 0.32, p = 0.03) but not with the GDS non-apathy score (r = 0.23, p = 0.13)

Summary

Introduction

In aMCI and AD dementia, apathy is associated with an increased risk for disease progression and poor functional outcomes (Boyle et al, 2003; Teng et al, 2007; Lanctôt et al, 2016). In MCI patients, impairment in more than one cognitive domain was associated with increased severity of apathy (Di Iulio et al, 2010). Unraveling the two syndromes, previous studies have shown that apathy is associated with a higher risk of functional impairment and disease progression independent of depression (Vicini Chilovi et al, 2009; Palmer et al, 2010; Richard et al, 2012). Sub-clinical apathy in healthy subjects is associated with changes in WM (Spalletta et al, 2013) as well as task-related functional magnetic resonance imaging (MRI) activation (Klaasen et al, 2017). These multimodal reports suggest the likely regions underlying apathy. The neurochemical changes, which have been well-characterized in aMCI and AD (Kantarci et al, 2013), associated with apathy are not known

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