# Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology

**Authors:** Isadora Cristina Ribeiro, Brenda Costa Gonçalves, Ítalo Karmann Aventurato, Marjorie Cristina Rocha da Silva, Liara Rizzi, Ana Luiza Gonçalves Rochetti, Gustavo Bruniera Peres Fernandes, Fernando Cendes, Marcio Luiz Figueredo Balthazar

PMC · DOI: 10.1055/s-0046-1817040 · 2026-03-11

## TL;DR

This study explores how cognitive performance and brain structure differ among older adults with different Alzheimer's disease pathophysiology classifications.

## Contribution

The study identifies cognitive differences between AT(N) classification groups and links memory to cortical thickness in the AD continuum group.

## Key findings

- The suspected non-AD pathophysiology group performed worse in attention/executive function than the AD continuum and normal biomarkers groups.
- Memory was associated with left fusiform gyrus thickness in the AD continuum group.
- Cortical thickness did not differ significantly among the AT(N) classification groups.

## Abstract

The diagnosis of predementia stages indicates an increased risk of progression to dementia. The Amyloid, Tau, and Neurodegeneration AT(N) classification considers measurements of altered proteins and the presence of neurodegeneration to classify the risk groups regarding the pathophysiology of Alzheimer's disease (AD). The cognitive and anatomical characteristics of the patients in the predementia stage according to the AT(N) classification are not fully understood.

To investigate whether there are differences in the clinical and anatomical profiles among older adults in the predementia stage according to the ATN classification, and to investigate the associations involving cognition and cortical thickness and subcortical volume in the AT(N) groups.

In total, 72 older adults with subjective cognitive decline and mild cognitive impairment were allocated to groups according to the AT(N) classification (AD continuum: n = 37; suspected non-AD pathophysiology: n = 8; normal biomarkers: n = 27). The participants were investigated through cognitive tests, magnetic resonance imaging scans, and cerebrospinal fluid analyses. We used multivariate and univariate analyses with post-hoc testing to verify differences among groups. In addition, linear regressions were performed to verify the interactions involving cognition and gray matter metrics.

The suspected non-AD pathophysiology group showed worse performance in attention/executive function than the AD continuum and normal biomarkers groups (
p
 = 0.04). However, the ATN classification groups did not differ in terms of cortical thickness (
p
 > 0.05). In addition, in the AD continuum group, memory was associated with left fusiform gyrus thickness (
p
 = 0.000 uncorrected; r = 0.238).

Cognition, but not gray matter metrics, differs among AT(N) classification groups. Memory is associated with cortical thickness in patients with positive amyloid Beta (AD continuum).

## Linked entities

- **Diseases:** Alzheimer's disease (MONDO:0004975), dementia (MONDO:0001627)

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** dementia (MESH:D003704), cognitive decline (MESH:D003072), ATN (MESH:C537728), Neurodegeneration (MESH:D019636), AD (MESH:D000544)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12978987/full.md

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Source: https://tomesphere.com/paper/PMC12978987