Abstract Background Cardiovascular disease (CVD) contributes to dementia risk, as cerebrovascular dysfunction and systemic inflammation play key roles in cognitive decline. Neurodegenerative changes, including tau accumulation, begin decades before clinical symptoms emerge, making midlife a critical period for identifying at-risk individuals. Understanding the interplay between vascular health, inflammation, and cognition in midlife adults with CVD is essential for early intervention and prevention strategies. Purpose This study examines the associations between CVD burden, inflammation, and cognitive function in middle-aged adults with CVD to identify early markers of dementia risk. Methods A cross-sectional analysis was conducted as part of an ongoing study enrolling middle-aged adults with CVD. CVD burden was assessed using a composite score of CV risk factors. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), Trail Making Test A visuospatial ability), Rey-Osterrieth Complex Figure Test (Rey-O; visuospatial), Multilingual Naming Test (MINT; language), and Mental Rotation Test (MRT; spatial reasoning). Plasma biomarkers of neurodegeneration (total tau t-tau and p-tau217) and inflammation (C-reactive protein CRP, triggering receptor expressed on myeloid cells TREM-1, interleukin IL-1β) were measured via ELISA. Results Participants (N=40) were 66±8 years of age, 55% female, and 38% Black and African American. CVD burden was positively associated with t-tau (r=.595, p.001) and p-tau217 (r=.623, p.001). Elevated t-tau and p-tau217 levels correlated with longer times on Trails B (t-tau: r=.425, p=.006; p-tau217: r=.431, p=.006). Diastolic blood pressure was associated with lower global cognition (MoCA: r=-.344, p=.030) and higher t-tau (r=.459, p=.003). Higher IL-1β levels were associated with poorer visuospatial performance (JOLO: r=-.449, p=.004; Rey-O: r=-.346, p=.029), reduced language ability (MINT: r=-.459, p=.003), and slower processing speed (Trails A: r=.349, p=.027). CRP was negatively associated with spatial reasoning (MRT: r=-.386, p=.014). Conclusions These preliminary findings suggest CVD burden and inflammation may contribute to early neurodegenerative processes and cognitive dysfunction in midlife adults, a critical window for dementia prevention. Elevated markers of neurofibrillary tangles (p-tau217) and global neurodegeneration (t-tau) indicate CVD may accelerate brain pathology decades before clinical symptoms emerge. Cognitive decline in this population appears most pronounced in executive function, processing speed, and visuospatial abilities, domains affected in both AD and vascular cognitive impairment. Given the increasing recognition of heart-brain interactions, cognitive screening should be integrated into CVD management, particularly for individuals with high inflammatory burden or vascular dysfunction.
Butts et al. (Sat,) studied this question.