Seed-based morphometry of nodes in the default mode network among patients with Alzheimer’s disease in Klang Valley, Malaysia

The default mode network (DMN) is a prominent neural network in the human brain that exhibits a substantial association with Alzheimer’s disease (AD). Functional connectivity (FC) and grey matter volume (GMV) were reported to differ between AD and healthy controls (HC). Nevertheless, available evidence is scarce regarding the structural and functional alterations observed in individuals diagnosed with Alzheimer’s disease (AD) within the context of Malaysia. A prospective cross-sectional study was conducted in the Klang Valley region of Malaysia. A total of 22 participants were enlisted for the study, following a thorough clinical assessment completed by geriatricians. The participants underwent a series of neuropsychological tests, including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR). The participants were classified into two groups, namely AD (Alzheimer’s disease) and HC (healthy controls), before the acquisition of resting-state functional magnetic resonance imaging (Rs-fMRI) images. The analysis of voxel-based morphometry (VBM) was conducted using SPM 12, a widely used software package in the field of neuroimaging, implemented in MATLAB. The primary objective of this analysis was to assess the grey matter volume (GMV). The CONN toolbox was employed to assess the functional connectivity (FC) and activation patterns of the nodes inside the default mode network (DMN). In this pilot project, a cohort of 22 participants was enlisted, consisting of 11 individuals with Alzheimer’s disease (AD) with an age range of 64-84 years (mean age 76.36 ± 0.52) and 11 healthy controls (HC) with an age range of 64-79 years (mean age 69.91 ± 5.34). In the Alzheimer’s disease (AD) group, there was a reduction in grey matter volume (GMV) observed in several brain regions when compared to the healthy control (HC) group. Specifically, decreased GMV was found in the right and left inferior temporal gyrus, left superior frontal gyrus, right superior frontal gyrus medial segment, right gyrus rectus, right temporal lobe, left putamen, and right precuneus, respectively. The significance level for the Rs-FC analysis was established at a cluster-size corrected p-value of less than 0.05. A notable reduction in the activation of the nodes within the default mode network (DMN) was observed in individuals with Alzheimer’s disease (AD) compared to healthy controls (HC). This drop was notably evident in the functional connectivity of the precuneus and anterior cingulate cortex in both AD and HC groups, as well as in the comparison between AD and HC groups. Resting-state functional magnetic resonance imaging (fMRI) can identify specific imaging biomarkers associated with Alzheimer’s disease by analysing grey matter volume (GMV) and default mode network (DMN) functional connectivity (FC) profiles. Consequently, there is promise for utilising resting- state fMRI as a non-invasive approach to enhance the detection and diagnosis of Alzheimer’s disease within the Malaysian community. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded by the Fundamental Research Grant Scheme (FRGS 06-02-14-1497FR/5524581) awarded by the Malaysian Ministry of Higher Education under grant number 5540244. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical clearance: This study was approved by the Ethics Committee of Research Involving Human Participants of Universiti Putra Malaysia (JKEUPM-2019-328) and MREC (NMRR-19-2719-49105). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.