Cortical and behavioral correlates of alexia in primary progressive aphasia and Alzheimer's disease

Aaron M Meyer; Sarah F Snider; Andreia V Faria; Donna C Tippett; Ryan Saloma; Peter E Turkeltaub; Argye E Hillis; Rhonda B Friedman

doi:10.1016/j.neuropsychologia.2025.109066

Cortical and behavioral correlates of alexia in primary progressive aphasia and Alzheimer's disease

Neuropsychologia. 2025 Jan 29:207:109066. doi: 10.1016/j.neuropsychologia.2025.109066. Epub 2025 Jan 3.

Authors

Aaron M Meyer¹, Sarah F Snider², Andreia V Faria³, Donna C Tippett⁴, Ryan Saloma², Peter E Turkeltaub², Argye E Hillis⁵, Rhonda B Friedman²

Affiliations

¹ Center for Aphasia Research and Rehabilitation, Georgetown University Medical Center, USA. Electronic address: [email protected].
² Center for Aphasia Research and Rehabilitation, Georgetown University Medical Center, USA.
³ Department of Radiology, Johns Hopkins University, USA.
⁴ Department of Physical Medicine and Rehabilitation, Johns Hopkins University, USA; Department of Neurology, Johns Hopkins University, USA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, USA.
⁵ Department of Neurology, Johns Hopkins University, USA.

PMID: 39756511
DOI: 10.1016/j.neuropsychologia.2025.109066

Abstract

The underlying causes of reading impairment in neurodegenerative disease are not well understood. The current study seeks to determine the causes of surface alexia and phonological alexia in primary progressive aphasia (PPA) and typical (amnestic) Alzheimer's disease (AD). Participants included 24 with the logopenic variant (lvPPA), 17 with the nonfluent/agrammatic variant (nfvPPA), 12 with the semantic variant (svPPA), 19 with unclassifiable PPA (uPPA), and 16 with AD. Measures of Surface Alexia and Phonological Alexia were computed by subtracting control-condition word reading accuracy from irregular word reading and pseudoword reading accuracy, respectively. Cases of Surface Alexia were common in svPPA, lvPPA, uPPA, and AD, but not in nfvPPA. At the subgroup level, average Surface Alexia was significantly higher in svPPA, lvPPA, and uPPA, compared to unimpaired age-matched controls. Cases of Phonological Alexia were common in nfvPPA, lvPPA, and uPPA, and average Phonological Alexia was significantly higher in these subgroups, compared to unimpaired age-matched controls. Behavioral regression results indicated that Surface Alexia can be predicted by impairment in the lexical-semantic processing of nouns, suggesting that a lexical-semantic deficit is required for the development of surface alexia, while cortical volume regression results indicated that Surface Alexia can be predicted by reduced volume in the left Superior Temporal Pole, which has been associated with conceptual-semantic processing. Behavioral regression results indicated that Phonological Alexia can be predicted by impairment on Pseudoword Repetition, suggesting that this type of reading difficulty may be due to impaired phonological processing. The cortical volume regression results suggested that Phonological Alexia can be predicted by reduced volume within the left Inferior Temporal Gyrus and the left Angular Gyrus, areas that are associated with lexical-semantic processing and phonological processing, respectively.

Keywords: Alzheimer's disease; Phonological alexia; Primary progressive aphasia; Surface alexia.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease* / complications
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / pathology
Alzheimer Disease* / physiopathology
Aphasia, Primary Progressive* / diagnostic imaging
Aphasia, Primary Progressive* / pathology
Aphasia, Primary Progressive* / physiopathology
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / pathology
Cerebral Cortex / physiopathology
Dyslexia / diagnostic imaging
Dyslexia / etiology
Dyslexia / pathology
Dyslexia / physiopathology
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neuropsychological Tests
Reading*