Navigating the stages of objective memory impairment (SOMI) through the Papez circuit: hippocampal brain reserve, white matter microstructure, and structural network topology along the Alzheimer’s continuum

Abstract Background: Alzheimer's disease (AD) unfolds across a spectrum of neurodegeneration, known as the AD continuum, starting several decades before presenting clinical symptoms. The Stages of Objective Memory Impairment (SOMI) is a method used to classify cognitive decline, ranging from negligible impairment to levels indicative of dementia. Identifying individuals at risk for developing AD dementia is crucial for early intervention and potential prevention of cognitive decline. Aim: This study uses SOMI staging to correlate neural indicators of neurodegeneration by analyzing neuropsychological tests and hippocampal-based brain reserve. We novelly assessed the link between SOMI staging and diffusion-based white matter microstructure metrics and network analytic graph theoretical metrics to examine topological network alterations across the AD continuum. Methods: 91 participants from the Alzheimer's and music therapy (ALMUTH) study were categorized from SOMI stages 0 through 4. Region-of-interest analyses focused on the Papez circuit, a limbic circuit focused on cognitive processing linked to AD-related neurodegeneration. SOMI stages were associated with neuropsychological measurements, hippocampal-based brain reserve using volumetric analysis, white matter microstructure (fractional anisotropy, FA, and mean diffusivity, MD) in the Papez circuit, and structural network analyses. Results: SOMI stages significantly correlated with most neuropsychological measures, hippocampal-based brain reserve, FA and MD differences across the Papez circuit, and altered network topological features locally and globally. Conclusion: Our findings offer new insights into early and progressive alterations of brain function associated with cognitive processing in AD, emphasizing the potential utility of translating these neural indicators for identifying at-risk individuals using non-invasive SOMI staging methods as aids in developing targeted interventions to slow or prevent disease progression. Trial Registration: Norsk Forskningsråd (NFR) funded. Regional Committees for Medical and Health Research Ethics (REC-WEST: reference number 2018/206). Clinicaltrials.gov: NCT03444181 (registered retrospectively 23 February 2018).