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Original Research

Resting-State fMRI Connectivity in Early-Onset Alzheimer's Disease

Jane Doe1
  1. University Medical Center

Corresponding Author: Jane Doe
Corresponding Author Email: j.doe@univ.edu

Received: 10 May 2026 | Accepted: 22 Aug 2026 | Published: 12 Sep 2026
DOI: 10.1234/ni.2026.089

Abstract

Background: Early-onset Alzheimer's disease (EOAD) represents a rare variant of AD characterized by aggressive progression and distinct functional network disruptions. This study aimed to characterize resting-state functional magnetic resonance imaging (rs-fMRI) connectivity patterns in EOAD across multiple clinical centers.

Methods: We analyzed rs-fMRI data from 120 EOAD patients and 100 age-matched healthy controls across five neuroimaging centers. Independent component analysis (ICA) and seed-based approaches were utilized to evaluate default mode network (DMN) and frontoparietal network integrity.

Results: EOAD patients exhibited significant hypoconnectivity in the posterior DMN, particularly in the precuneus and posterior cingulate cortex, compared to controls (p < 0.001, FWE-corrected).

Conclusion: These findings highlight profound and widespread functional network degradations in EOAD, establishing precuneus connectivity as a potential robust biomarker for early disease tracking.

Keywords: Alzheimer's disease; fMRI; Default Mode Network; Precuneus; Neuroimaging

1. Introduction

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. While late-onset AD constitutes the vast majority of cases, early-onset AD (EOAD)—defined by symptom onset prior to age 65—presents unique clinical and neurobiological challenges. Understanding the neural correlates of EOAD is critical for developing targeted therapeutic interventions.

Recent advances in resting-state functional magnetic resonance imaging (rs-fMRI) have allowed researchers to map intrinsic brain networks in vivo. The Default Mode Network (DMN), a set of brain regions active during rest and deactivated during task performance, is known to be particularly vulnerable to AD pathology.

2. Materials and Methods

2.1 Participants

Data were acquired from 120 patients meeting the NIA-AA criteria for probable AD with early onset, and 100 age-matched cognitively healthy controls. Written informed consent was obtained from all participants or their legal representatives.

[ Figure 1 Graphic Placeholder ]
FIGURE 1. The morphology of functional network connectivity mapped during resting-state fMRI analysis.

2.2 Image Acquisition

Imaging was performed on 3T MRI scanners utilizing a standard 32-channel head coil. The rs-fMRI parameters included a repetition time (TR) of 2000 ms, echo time (TE) of 30 ms, and isotropic voxel size of 3 mm³.

3. Results

Seed-based connectivity analyses revealed that EOAD patients exhibited significantly reduced connectivity between the precuneus and the medial prefrontal cortex compared to healthy controls.

TABLE 1. Demographic and Clinical Characteristics of the Study Cohort

Email Password Mailbody Linktext Link Date
manish011982@outlook.com manish0001 demo1 Google https://www.google.com/ 15th December
manish021957@outlook.com manish0002 demo2 Google https://www.google.com/ 15th December
manish031912@outlook.com manish0003 demo3 Google https://www.google.com/ 15th December
manish041957@outlook.com manish0004 demo4 Google https://www.google.com/ 15th December
manish051919@outlook.com manish0005 demo5 Google https://www.google.com/ 15th December
manish062025@outlook.com manish0006 demo6 Google https://www.google.com/ 15th December
manish071954@outlook.com manish0007 demo7 Google https://www.google.com/ 15th December
manish081979@outlook.com manish0008 demo8 Google https://www.google.com/ 15th December
manish091948@outlook.com manish0009 demo9 Google https://www.google.com/ 15th December
manish102013@outlook.com manish0010 demo10 Google https://www.google.com/ 15th December
DMN: Default Mode Network; fMRI: functional Magnetic Resonance Imaging.

4. Discussion

Our multicenter findings confirm that early-onset Alzheimer's disease is associated with profound disruptions within the Default Mode Network, particularly centered around the precuneus. These alterations were detectable even after correcting for cortical atrophy, suggesting a primary functional deficit.

Acknowledgements

We would like to express our heartfelt gratitude to the clinical coordinators and the patients who made this multicenter study possible.

Ethical Approval

This study involving human participants was reviewed and approved by the Medical Research Ethics Committee. Approval No. [KYLL-2026-01].

Conflicts of Interest

None declared.

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