# Exploring neural correlates of automated speech-based cognitive markers through resting-state functional connectivity in aging and at-risk Alzheimer’s disease

**Authors:** Qingyue Li, Zampeta-Sofia Alexopoulou, Martin Dyrba, Elisa Mallick, Johannes Tröger, Eike Spruth, Slawek Altenstein, Claudia Bartels, Wenzel Glanz, Enise I. Incesoy, Michaela Butryn, Ingo Kilimann, Sebastian Sodenkamp, Franziska Maier, Ayda Rostamzadeh, Antje Osterrath, Josef Priller, Anja Schneider, Jens Wiltfang, Christoph Laske, Björn Falkenburger, Michael Wagner, Emrah Duezel, Annika Spottke, Gabor C. Petzold, Frank Jessen, Alexandra König, Stefanie Köhler, Stefan Teipel

PMC · DOI: 10.1186/s13195-026-01993-x · 2026-02-24

## TL;DR

This study explores how speech-based cognitive assessments relate to brain connectivity patterns in aging and Alzheimer’s disease, finding limited utility for detecting functional changes.

## Contribution

The study introduces a novel approach linking automated speech features with resting-state brain connectivity in Alzheimer’s disease.

## Key findings

- Greater language network connectivity in the left middle temporal gyrus was associated with increased semantic verbal fluency switching.
- Individual speech features showed network-specific associations with executive, language, and default mode networks.
- Digital speech assessments currently have limited utility for detecting functional connectivity alterations in at-risk individuals.

## Abstract

Digital speech-based assessments provide scalable tools for detecting subtle cognitive decline. Here, we investigated whether digitally derived speech-based composite score of cognition and individual speech features were associated with alterations in functional connectivity (FC) within task-related brain networks in the Alzheimer’s disease spectrum, which are known to reflect cognitive performance and disease-related changes.

Data were analyzed from 129 participants of the German PROSPECT-AD study, ranging from cognitively healthy individuals to those with mild cognitive impairment. Speech-based cognitive scores and speech features were derived from automated phone-administered semantic verbal fluency (SVF) and verbal learning tasks (VLT). Resting-state fMRI assessed FC, with intrinsic connectivity networks identified via independent component analysis and dual regression. Associations were examined using permutation-based voxel-wise regression, controlling for demographic and clinical covariates. Seed-to-voxel analyses were conducted to support network identification and complement findings.

Greater language network connectivity in the left middle temporal gyrus was associated with increased SVF temporal cluster switching (FWE < .05, cluster size = 12 voxels, mean T = 3.86). Exploratory analyses (uncorrected p < .01) demonstrated no significant associations between cognitive composite scores and FC. However, individual SVF and VLT speech features exhibited network-specific associations across executive, language, and default mode networks, indicating exploratory yet spatially distinct connectivity patterns.

Digital speech-based assessments may have limited current utility for detecting FC alterations in at-risk individuals. Further validation using complementary methodological approaches, shorter intervals between fMRI and speech assessments, and testing in independent cohorts, are essential to establish their reliability and clinical relevance for monitoring brain network changes.

The online version contains supplementary material available at 10.1186/s13195-026-01993-x.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** SYNM (synemin) [NCBI Gene 23336] {aka DMN, SYN}, DGCR2 (DiGeorge syndrome critical region gene 2) [NCBI Gene 9993] {aka DGS-C, IDD, LAN, SEZ-12}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** -C (OMIM:211750), brain dysfunctions (MESH:D001927), SVF (MESH:D013064), ECN (MESH:C536209), executive dysfunction (MESH:D006331), amyloid (MESH:C000718787), dementia (MESH:D003704), SCD (MESH:D003072), episodic memory impairment (MESH:D008569), HC (MESH:D000067329), psychiatric disorders (MESH:D001523), substance abuse (MESH:D019966), brain atrophy (MESH:C566985), AD (MESH:D000544), MCI (MESH:D060825), TFCE (MESH:C564835)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961854/full.md

---
Source: https://tomesphere.com/paper/PMC12961854