White Matter Deterioration May Foreshadow Impairment of Emotional Valence Determination in Early-Stage Dementia of the Alzheimer Type

Abstract

In Alzheimer Disease (AD), non-verbal skills often remain intact for far longer than verbally mediated processes. Four (1 female, 3 males) participants with early-stage Clinically Diagnosed Dementia of the Alzheimer Type (CDDAT) and eight neurotypicals (NTs; 4 females, 4 males) completed the emotional valence determination test (EVDT) while undergoing BOLD functional magnetic resonance imaging (fMRI). We expected CDDAT participants to perform just as well as NTs on the EVDT, and to display increased activity within the bilateral amygdala and right anterior cingulate cortex (r-ACC). We hypothesized that such activity would reflect an increased reliance on these structures to compensate for on-going neuronal loss in frontoparietal regions due to the disease. We used diffusion tensor imaging (DTI) to determine if white matter (WM) damage had occurred in frontoparietal regions as well. CDDAT participants had similar behavioral performance and no differences were observed in brain activity or connectivity patterns within the amygdalae or r-ACC. Decreased fractional anisotropy (FA) values were noted, however, for the bilateral superior longitudinal fasciculi and posterior cingulate cortex (PCC). We interpret these findings to suggest that emotional valence determination and non-verbal skill sets are largely intact at this stage of the disease, but signs foreshadowing future decline were revealed by possible WM deterioration. Understanding how non-verbal skill sets are altered, while remaining largely intact, offers new insights into how non-verbal communication may be more successfully implemented in the care of AD patients and highlights the potential role of DTI as a presymptomatic biomarker.

Keywords: Alzheimer; DTI; brain networks; chimeric faces; emotional valence; fMRI.

Figure 1

Examples of the emotional valence determination test (EVDT). EVDT examples in response to the question: “Are the emotions the same?” (left) “yes”; two neutral faces. (center) “yes”; two happy faces. (right) “no”; happy (top) and neutral (bottom).

Figure 2

(A) Results of Rey-Osterrieth Complex Figure B-Visuospatial Memory Test (ROCFB-VMT) and EVDT. (B) ROCFB-VMT and EVDT performance were not correlated Pearson Correlation r = 0.022, p_correlation = 0.648. NT, Neurotypicals; CDDAT, Clinically diagnosed dementia of the Alzheimer Type.

Figure 3

Pertinent diffusion tensor imaging (DTI) results for the EVDT. Significant differences were seen in the posterior cingulate cortex (PCC; light blue crescent, top) and superior longitudinal fasciculi (blue crescent, bottom), but not anterior cingulate (red crescent, top) or amygdaloidal connections (pink circle, bottom). Areas where NT > CDDAT for fractional anisotropy (FA) measures are shown in red. Green lines represent the FA skeleton. NT, Neurotypicals; CDDAT, Clinically Diagnosed Dementia of the Alzheimer Type.