Irregular word reading as a marker of semantic decline in Alzheimer's disease: implications for premorbid intellectual ability measurement

Alzheimers Res Ther. 2024 May 2;16(1):96. doi: 10.1186/s13195-024-01438-3.


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 primary objective of this study is to ascertain whether irregular word reading serves as an indicator of cognitive and semantic decline in AD, potentially discouraging its use as a marker for premorbid intellectual abilities.

Method: Six hundred eighty-one 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), a region implicated in semantic memory.

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: While the AmNART may be appropriate to measure premorbid intellectual abilities in cognitively unimpaired individuals, our results suggest that it captures current semantic decline in MCI and AD patients and may therefore underestimate premorbid intelligence. On the other hand, irregular word reading tests might be clinically useful to detect semantic impairments in individuals on the AD continuum.

Keywords: Alzheimer’s dementia; Deformation-based morphometry; Exception word; Irregular word; Mild cognitive impairment; Neuropsychology; Premorbid intelligence; Reading; Semantic; Verbal intelligence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / psychology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / psychology
  • Female
  • Humans
  • Intelligence / physiology
  • Magnetic Resonance Imaging*
  • Male
  • Neuropsychological Tests*
  • Reading*
  • Semantics*