Irregular word reading as a marker of cognitive and semantic decline in Alzheimer's disease rather than an estimate of premorbid intellectual abilities

Abstract

Background: Irregular word reading has been used to estimate premorbid intelligence in Alzheimer's disease (AD) dementia. However, reading models highlight the core influence of semantic abilities on irregular word reading, which shows early decline in AD. The general aim of this study is to determine whether irregular word reading is a valid estimate of premorbid intelligence, or a marker of cognitive and semantic decline in AD.

Method: 681 healthy controls (HC), 104 subjective cognitive decline, 290 early and 589 late mild cognitive impairment (EMCI, LMCI) and 348 AD participants from the Alzheimer's Disease Neuroimaging Initiative were included. Irregular word reading was assessed with the American National Adult Reading Test (AmNART). Multiple linear regressions were conducted predicting AmNART score using diagnostic category, general cognitive impairment and semantic tests. A generalized logistic mixed-effects model predicted correct reading using extracted psycholinguistic characteristics of each AmNART words. Deformation-based morphometry was used to assess the relationship between AmNART scores and voxel-wise brain volumes, as well as with the volume of a region of interest placed in the left anterior temporal lobe (ATL).

Results: EMCI, LMCI and AD patients made significantly more errors in reading irregular words compared to HC, and AD patients made more errors than all other groups. Across the AD continuum, as well as within each diagnostic group, irregular word reading was significantly correlated to measures of general cognitive impairment / dementia severity. Neuropsychological tests of lexicosemantics were moderately correlated to irregular word reading whilst executive functioning and episodic memory were respectively weakly and not correlated. Age of acquisition, a primarily semantic variable, had a strong effect on irregular word reading accuracy whilst none of the phonological variables significantly contributed. Neuroimaging analyses pointed to bilateral hippocampal and left ATL volume loss as the main contributors to decreased irregular word reading performances.

Conclusions: Irregular word reading performances decline throughout the AD continuum, and therefore, premorbid intelligence estimates based on the AmNART should not be considered accurate in MCI or AD. Results are consistent with the theory of irregular word reading impairments as an indicator of disease severity and semantic decline.

Keywords: Alzheimer’s dementia; deformation-based morphometry; exception word; irregular word; mild cognitive impairment; neuropsychology; premorbid intelligence; reading; semantic; verbal intelligence.

Figure 1

Relation between AmNART error score and diagnostic category

Figure 2

A. Relation between MMSE and AmNART error score relative to diagnostic category B. Relation between MoCA and AmNART error score relative to diagnostic category Note. *: p < .05, **: p < .01, ***: p < .001.

Figure 3

A. Relation between Boston Naming Test and AmNART error score relative to diagnostic category B. Relation between Trail making part-B and AmNART error score relative to diagnostic category C. Relation between AVLT delayed recall and AmNART error score relative to diagnostic category Note. *: p < .05, **: p < .01, ***: p < .001.

Figure 4

Relation between voxel-wise DBM maps and AmNART error score Axial, coronal and sagittal slices showing the t-statistic maps reflecting the significant patterns of brain volume changes in the sample. Colour gradient indicates shrinkage of the tissue (i.e., atrophy). X, Y and Z values indicate MNI coordinates for the displayed slice.