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Abstract: Objectives<br>Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA),<br>white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative,<br>artificial intelligence (AI)-based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls.<br><br>Methods<br>A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed<br>at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate<br>(BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores<br>and imaging markers.<br><br>Results<br>AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in<br>multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as<br>the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%.<br><br>Conclusions<br>The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the<br>subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably<br>MTA, Fazekas score, and number of CMBs