Neuropsychiatric Deviations From Normative Profiles: An MRI-Derived Marker for Early Alzheimer's Disease Detection

Alzheimers disease (AD) is a brain disorder that develops slowly and mainly affects memory, thinking, language, and daily activities. It is one of the most common causes of dementia and creates many difficulties for patients as well as their families. In the early stage, the symptoms are often mild and may look like normal ageing. For this reason, many people are diagnosed late, when the disease has already progressed. At present, there is no complete cure for AD. Still, early detection can help doctors manage the condition better and take suitable steps at the right time. In this study, a machine learning model is proposed to detect the early stages of Alzheimers disease using clinical details, neuropsychological test scores, and neuroimaging-related measures. The data used in this work is collected from the Alzheimers Disease Neuroimaging Initiative (ADNI). As the dataset has missing values, iterative imputation is applied to fill them. The dataset also has class imbalance, which is handled using Borderline SVM-SMOTE. After that, feature selection is carried out using wrapper-based and embedded methods so that only important features are used for training. The selected features are divided into training and testing sets, and feature scaling is applied. A stacking ensemble model is developed using Logistic Regression, Extra Trees, Bagging KNN, and LightGBM as base classifiers. Along with this, an artificial neural network is also trained on the same dataset. The performance of these models is compared using precision, recall, F1-score, and AUC-ROC. This study aims to find the best classifier and also identify important biomarkers that may help in the early diagnosis of Alzheimers disease.

Multimodal neuroimaging combining structural MRI and positron emission tomography (PET) captures complementary structure-function relationships across the Alzheimer's disease (AD) continuum, yet existing artificial intelligence systems produce a single diagnostic label without quantifying which imaging modality drove that decision for a specific patient. We introduce the Modality Contribution Network (MCNet) and the Modality Contribution Score (MCS), the first per-patient attribution framework quantifying the shift in modality dominance from structural atrophy to amyloid and metabolic dysfunction across the cognitively normal to MCI to AD continuum. MCS is normalised to unity per subject via modality ablation (MCS_MRI_i + MCS_PET_i = 1.0 for every subject i), providing an interpretable, clinically actionable score that fluid biomarkers cannot supply. Applied to 327 ADNI-3 participants balanced across cognitively normal, mild cognitive impairment, and AD groups, MCNet achieved competitive three-class staging performance (AUC=0.881). The MCS revealed a statistically significant monotonic gradient (Kruskal-Wallis p<0.0001), with increasing PET dominance from cognitively normal (MCS_PET 0.412+/-0.229) through MCI (0.489+/-0.289) to AD (0.671+/-0.426), validated against amyloid SUVR (r=0.172, p=0.006) and FDG metabolic biomarkers (r=-0.287, p=0.0005) from separate imaging pipelines. External replication in 1,073 independent OASIS-3 subjects confirmed cross-cohort generalisability (H=166.99, p<0.0001, eta^2=0.156). A mechanistic comparison with SHAP demonstrated that ablation-based MCS captures clinically meaningful modality dependence that deviation-based methods cannot. These findings position MCNet as a foundation for personalised imaging decisions, clinical trial stratification, and trustworthy AI in dementia care.

Predicting which people with mild cognitive impairment (MCI) will develop dementia matters for starting treatment early, yet computational work on structural brain imaging has relied almost entirely on a single scan. We propose TAFNet, a temporal attention fusion network that combines a baseline and a follow-up T1-weighted scan. A pretrained Siamese encoder represents each scan, and a fusion module combines the two through anatomical difference, cross-temporal attention and joint context, mixed by a learned per-patient gate. We evaluate it on paired scans from participants with MCI in the Alzheimer's Disease Neuroimaging Initiative, taken up to two years apart, with a dementia diagnosis within three years of the first scan as the outcome. The evaluation is designed to hold up under scrutiny: conversion is defined from recorded diagnoses, the pretraining pool shares no participants with the evaluation cohort, a held-out test partition is kept apart from model development, and uncertainty is estimated by resampling participants. TAFNet discriminates converters from non-converters well on the held-out partition. It outperforms conventional single-scan networks and a model that subtracts the two scans; both differences are significant in cross-validation and have the same direction on the smaller held-out partition. With everything else held fixed, adding the follow-up scan gives a significant gain in cross-validation. Against a recurrent CNN-LSTM baseline built on the same encoder, TAFNet performs comparably, with neither model consistently ahead. Operating points chosen on validation data, in place of the default threshold, give high sensitivity at a clinically reasonable specificity.