G‐ALPS: An index for evaluating cognitive decline and aging using diffusion tensor imaging

INTRODUCTION: The glymphatic system dysfunction is associated with cognitive decline in neurodegenerative diseases such as Alzheimer's disease (AD). METHODS: We introduce the G-Along Perivascular Space (G-ALPS) index, an optimized version of the ALPS index derived using Genetic Programming, and use it to analyze 217 diffusion tensor imaging (DTI) samples. RESULTS: Compared to the ALPS, the proposed G-ALPS index shows a stronger correlation with cognitive measures, including Mini-Mental State Examination (MMSE, 2.78% improvement), Clinical Dementia Rating (CDR, 5.13% improvement), and Functional Activities Questionnaire (FAQ, 10% improvement), as demonstrated by the analysis of fiber diffusivities in DTI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Furthermore, the G-ALPS exhibits enhanced sensitivity in identifying the effects of aging (94.81% improvement in AD individuals, 105% improvement in patients with mild cognitive impairment [MCI], and 81.25% improvement in normal controls) and sleep-related disorders (21.27% improvement in correlation with MMSE, and 2.53% improvement in correlation with Pittsburgh Sleep Quality Index [PSQI]) using the Human Connectome Project (HCP) dataset. DISCUSSION: Our results suggest that the G-ALPS index may be an indirect metric for assessing the glymphatic system's function or dysfunction.