Imaging Biomarkers in Neurodegenerative Diseases: A Systematic Review of MRI and PET in Early Detection and Disease Monitoring

Abstract Neurodegenerative diseases are characterized by progressive neuronal loss and represent a growing global health burden. Early diagnosis and accurate disease monitoring remain major clinical challenges, as pathological changes often precede overt symptoms by several years. Advanced neuroimaging techniques, particularly magnetic resonance imaging (MRI) and positron emission tomography (PET), have emerged as key sources of imaging biomarkers capable of capturing structural, functional, metabolic, and molecular alterations associated with neurodegeneration. A systematic literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science from inception to the final search date. Eligible studies included original human research evaluating MRI- and/or PET-based imaging biomarkers in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Data extraction focused on imaging modalities, biomarkers assessed, clinical applications, and outcomes related to diagnosis and disease progression. Methodological quality and risk of bias were assessed using QUADAS-2 for diagnostic accuracy studies and design-appropriate criteria for longitudinal and prognostic studies. A qualitative narrative synthesis was performed due to methodological heterogeneity. Across the included studies, MRI- and PET-based biomarkers demonstrated complementary roles along the neurodegenerative disease continuum. Structural MRI markers, such as regional brain atrophy and cortical thinning, were consistently associated with disease severity and longitudinal progression, while diffusion and functional MRI detected microstructural and network-level alterations at earlier stages. PET imaging revealed disease-specific metabolic and molecular patterns, with FDG-PET identifying characteristic hypometabolism and amyloid-β and tau PET enabling in vivo detection of pathological protein deposition before clinical symptom onset. Multimodal MRI–PET approaches improved diagnostic accuracy and prognostic stratification compared with single-modality analyses. However, substantial heterogeneity in imaging protocols, analytical methods, and study populations was observed. MRI and PET provide robust and complementary imaging biomarkers for early detection and disease monitoring in neurodegenerative diseases. While PET biomarkers are particularly sensitive to early molecular pathology, MRI markers are well-suited for longitudinal tracking of neurodegeneration. Integration of multimodal imaging within standardized frameworks may enhance clinical translation, improve patient stratification, and support precision medicine approaches in neurodegenerative disorders. Further large-scale, harmonized longitudinal studies are required to validate and standardize imaging biomarkers for routine clinical use.