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Clinical Manifestations.

Siddharth Nayak1, Mark E Wagshul1, Roee Holtzer2

  • 1Albert Einstein College of Medicine, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Mild cognitive impairment (MCI) impacts brain networks and cognitive function in older adults. Understanding these changes is crucial for early Alzheimer's disease detection and intervention strategies.

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Area of Science:

  • Neuroimaging
  • Cognitive Neuroscience
  • Gerontology

Background:

  • Alzheimer's disease (AD) research is focusing on the pre-clinical stage, specifically the transition from normal aging to mild cognitive impairment (MCI).
  • Characterizing brain-cognition associations with and without MCI is critical for understanding early AD pathophysiology.
  • This study investigates functional brain network alterations in older adults, considering MCI status.

Purpose of the Study:

  • To examine how mild cognitive impairment (MCI) affects brain-behavior relationships in older adults.
  • To identify specific brain networks associated with cognitive processing speed (Symbol Digit Modalities Test - SDMT) in individuals with and without MCI.
  • To explore functional connectivity patterns in the pre-clinical stage of Alzheimer's disease.

Main Methods:

  • 167 older adults (82 with MS, 85 controls) underwent resting-state functional MRI (rsfMRI) and structural MRI.
  • Group Independent Component Analysis (ICA) identified brain networks, with subject-specific expressions derived via dual regression.
  • Multiple linear regressions analyzed the association between network expression scores and SDMT performance.

Main Results:

  • In the overall sample, the SMN, LFPN, and salience networks were associated with SDMT performance.
  • In individuals with MS, SMN and medial visual networks correlated with SDMT; no significant associations were found in controls.
  • When excluding MCI participants, LFPN and RFPN networks showed associations with SDMT. In controls without MCI, RFPN, LFPN, and salience networks were linked to SDMT.

Conclusions:

  • MCI status significantly influences brain-cognition associations in older adults.
  • Findings highlight dynamic functional connectivity changes during the pre-clinical stage of Alzheimer's disease.
  • This research provides insights into neurobiological markers for early AD detection.