6th Edition of Neurology World Conference 2026

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease with a non-linear pathophysiological dynamic, culminating in symptomatic late stages with cognitive and behavioural decline. Amyloid-β (Aβ) and tau proteinopathies are the neuropathological hallmarks of AD.
Neuropsychiatric symptoms (NPS  ) such as depression, apathy, aggression, psychosis, and sleep-wake disturbances are core features of AD alongside prominent memory loss. Neuropsychiatric symptoms (NPS) have been increasingly detected as early non-cognitive indicators of the AD continuum.  We investigated AD pathology at the prodromal symptomatic stage, under NPS, before converting to AD dementia.  
A total of 139 elderly individuals were stratified based on the global depression scale (GDSCALE), neuropsychiatric inventory total scores (NPITOT), clinical dementia rating (CDR) and mini-mental status examination (MMSE), into 12 mild cognitive impairment (MCI) individuals with NPS (MCI+) and 49 without NPS (MCI-), 6 AD dementia patients with NPS (AD+), 23 AD individuals with NPS (AD-) but no cognitive impairment, and 49 age and sex-matched normal individuals.
MRI-based Voxel-Based Morphometry (VBM)  and DTI-based Tract-Based Spatial Statistics (TBSS) were first used to analyze brain-wide group differences. Second, the graph theoretical approach was used to investigate brain structural connectivity alterations. Moreover, correlational tractography was performed to identify White Matter (WM) diffusion metrics associated with AD CSF and plasma biomarkers. 
VBM showed significant volume reduction only in MCI+  individuals compared to normal controls in the left Hippocampus, Amygdala, and primary sensory cortex (SSC). No WM or Gray Matter (GM) abnormalities were detected in MCI- group. 
But in contrast to the VBM, structural connectivity estimation revealed structural WM connectivity loss in both hemispheres of MCI- individuals relative to normals, including the Thalamus, Pallidum, Putamen, Caudate, and hippocampus on the left side and SSC and frontal cortex on the right side, indicating limbic system involvement before overt volumetric GM loss.